GenomeX Data Exchange FHIR IG
0.2.0 - draft
GenomeX Data Exchange FHIR IG, published by MITRE. This guide is not an authorized publication; it is the continuous build for version 0.2.0 built by the FHIR (HL7® FHIR® Standard) CI Build. This version is based on the current content of https://github.com/CodeX-HL7-FHIR-Accelerator/GenomeX-DataExchange/ and changes regularly. See the Directory of published versions
Generated Narrative: Bundle PrenatalCollectionBundleSingle
Bundle PrenatalCollectionBundleSingle of type collection
Entry 1 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PractitionerLabDirector
Resource Practitioner:
Generated Narrative: Practitioner PractitionerLabDirector
identifier: National provider identifier/1750369955 (use: official, )
active: true
name: PractitionerJane Smith
gender: Female
address: Address 123 Boston MA 12345
Qualifications
Code Laboratory Director
Entry 2 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PatientMale
Resource Patient:
Generated Narrative: Patient PatientMale
version: 1; Last updated: 2024-09-25 00:02:13+0000;
Information Source: #mzuK1EHcvMPipAda
Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Active: true Contact Detail US (home)
Entry 3 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalVariant1SNPAlpha1ADPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalVariant1SNPAlpha1ADPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Variant
status: Final
category: Laboratory, Genetics
code: Genetic variant assessment
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
value: Present
method: Sequencing
component
code: Genetic variation clinical significance [Imp]
value: Pathogenic
component
code: Genomic source class [Type]
value: Germline
component
code: Variant category
value: Simple variant
component
code: Allelic state
value: Heterozygous
component
code: DNA change (c.HGVS)
value: NM_000295.4(SERPINA1):c.1096G>A(E366K, aka Z allele) heterozygote
component
code: Transcript reference sequence [ID]
value: NM_000295.4
component
code: DNA change type
value: Substitution
component
code: Genomic reference sequence identifier
value: NM_000295.4
component
code: Gene studied [ID]
value: SERPINA1
Entry 4 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalVariantAutosomalRecessiveSAoCSPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalVariantAutosomalRecessiveSAoCSPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Variant
status: Final
category: Laboratory, Genetics
code: Genetic variant assessment
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
value: Absent
method: Sequencing
component
code: Human reference sequence assembly version
value: GRCh37
component
code: Chromosome [Identifier] in Blood or Tissue by Molecular genetics method
value: Chromosome 13
component
code: Gene studied [ID]
value: SACS
Entry 5 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalVariantFamilialHyperinsulinismPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalVariantFamilialHyperinsulinismPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Variant
status: Final
category: Laboratory, Genetics
code: Genetic variant assessment
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
value: Absent
method: Sequencing
component
code: Human reference sequence assembly version
value: GRCh37
component
code: Chromosome [Identifier] in Blood or Tissue by Molecular genetics method
value: Chromosome 11
component
code: Gene studied [ID]
value: ABCC8
Entry 6 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalResidualRiskAlpha1ADPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalResidualRiskAlpha1ADPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
status: Final
occurrence: 2024-07-09
basis: Observation Genetic variant assessment
Predictions
Outcome Probability[x] Patient has a disease-causing mutation for alpha-1 antitrypsin deficiency 1
Entry 7 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalResidualRiskAutosomalRecessiveSAoCSPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalResidualRiskAutosomalRecessiveSAoCSPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
status: Final
occurrence: 2024-07-09
basis: Observation Genetic variant assessment
Predictions
Outcome Probability[x] Patient has a disease-causing mutation for autosomal recessive spastic ataxia of Charlevoix-Saguenay 0.00002277238382929289
Entry 8 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalResidualRiskFamilialHyperinsulinismPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalResidualRiskFamilialHyperinsulinismPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
status: Final
occurrence: 2024-07-09
basis: Observation Genetic variant assessment
Predictions
Outcome Probability[x] Patient has a disease-causing mutation for familial hyperinsulinism, ABCC8-related 0.00005850664934601126
Entry 9 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReproductivePostRiskAlpha1ADPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalReproductivePostRiskAlpha1ADPatientMale
version: 2; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
status: Final
occurrence: 2024-07-09
basis:
- RiskAssessment: status = final; occurrence[x] = 2024-07-09
- Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Predictions
Outcome Probability[x] Reproductive risk for inheriting a disease-causing mutation for alpha-1 antitrypsin deficiency after Prenatal test 0.009098611015817493 note: Residual risk is an estimate of each patient's post- test likelihood of being a carrier, while the reproductive risk represents an estimated likelihood that the patients' future children could inherit each disease. These risks are inherent to all carrier-screening tests, may vary by ethnicity, are predicated on a negative family history, and are present even given a negative test result. Inaccurate reporting of ethnicity may cause errors in risk calculation. In addition, average carrier rates are estimated using incidence or prevalence data from published scientific literature and/or reputable databases, where available, and are incorporated into residual risk calculations for each population/ethnicity. When population-specific data is not available for a condition, average worldwide incidence or prevalence is used. Further, incidence and prevalence data are only collected for the specified phenotypes (which include primarily the classic or severe forms of disease) and may not include alternate or milder disease manifestations associated with the gene. Actual incidence rates, prevalence rates, and carrier rates, and therefore actual residual risks, may be higher or lower than the estimates provided. Carrier rates, incidence/prevalence, and/or residual risks are not provided for some genes with biological or heritable properties that would make these estimates inaccurate. See the full clinical report for interpretation and details. The reproductive risk presented is based on a hypothetical pairing with a partner of the same ethnic group.
Entry 10 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReproductivePostRiskAutosomalRecessiveSAoCSPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalReproductivePostRiskAutosomalRecessiveSAoCSPatientMale
version: 2; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
status: Final
occurrence: 2024-07-09
basis:
- RiskAssessment: status = final; occurrence[x] = 2024-07-09
- Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Predictions
Outcome Probability[x] Reproductive risk for inheriting a disease-causing mutation for autosomal recessive spastic ataxia of Charlevoix-Saguenay after Prenatal test 1.1386256738067698E-8 note: Residual risk is an estimate of each patient's post- test likelihood of being a carrier, while the reproductive risk represents an estimated likelihood that the patients' future children could inherit each disease. These risks are inherent to all carrier-screening tests, may vary by ethnicity, are predicated on a negative family history, and are present even given a negative test result. Inaccurate reporting of ethnicity may cause errors in risk calculation. In addition, average carrier rates are estimated using incidence or prevalence data from published scientific literature and/or reputable databases, where available, and are incorporated into residual risk calculations for each population/ethnicity. When population-specific data is not available for a condition, average worldwide incidence or prevalence is used. Further, incidence and prevalence data are only collected for the specified phenotypes (which include primarily the classic or severe forms of disease) and may not include alternate or milder disease manifestations associated with the gene. Actual incidence rates, prevalence rates, and carrier rates, and therefore actual residual risks, may be higher or lower than the estimates provided. Carrier rates, incidence/prevalence, and/or residual risks are not provided for some genes with biological or heritable properties that would make these estimates inaccurate. See the full clinical report for interpretation and details. The reproductive risk presented is based on a hypothetical pairing with a partner of the same ethnic group.
Entry 11 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReproductivePostRiskFamilialHyperinsulinismPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalReproductivePostRiskFamilialHyperinsulinismPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
status: Final
occurrence: 2024-07-09
basis:
- RiskAssessment: status = final; occurrence[x] = 2024-07-09
- Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Predictions
Outcome Probability[x] Reproductive risk for inheriting a disease-causing mutation for familial hyperinsulinism, ABCC8-related after Prenatal test 8.53310747471998E-8 note: Residual risk is an estimate of each patient's post- test likelihood of being a carrier, while the reproductive risk represents an estimated likelihood that the patients' future children could inherit each disease. These risks are inherent to all carrier-screening tests, may vary by ethnicity, are predicated on a negative family history, and are present even given a negative test result. Inaccurate reporting of ethnicity may cause errors in risk calculation. In addition, average carrier rates are estimated using incidence or prevalence data from published scientific literature and/or reputable databases, where available, and are incorporated into residual risk calculations for each population/ethnicity. When population-specific data is not available for a condition, average worldwide incidence or prevalence is used. Further, incidence and prevalence data are only collected for the specified phenotypes (which include primarily the classic or severe forms of disease) and may not include alternate or milder disease manifestations associated with the gene. Actual incidence rates, prevalence rates, and carrier rates, and therefore actual residual risks, may be higher or lower than the estimates provided. Carrier rates, incidence/prevalence, and/or residual risks are not provided for some genes with biological or heritable properties that would make these estimates inaccurate. See the full clinical report for interpretation and details. The reproductive risk presented is based on a hypothetical pairing with a partner of the same ethnic group.
Entry 12 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PractitionerOrderingProvider
Resource Practitioner:
Generated Narrative: Practitioner PractitionerOrderingProvider
active: true
name: Laura Salma
address: 123 Main St. San Francisco CA 94080
Entry 13 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalGenomicStudyAnalysisAlpha1ADPatientMale
Resource Procedure:
Generated Narrative: Procedure PrenatalGenomicStudyAnalysisAlpha1ADPatientMale
version: 1; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
Profile: Genomic Study Analysis
org/fhir/uv/genomics-reporting/StructureDefinition/genomic-study-analysis-genomic-source-class: Germline
Genomic Study Analysis Genome Build: GRCh37
Genomic Study Analysis Regions
- description: Exons sequenced
- studied: Exons: NM_000295:2-5
Genomic Study Analysis Regions
- description: Genes studied
- studied: SERPINA1
Genomic Study Analysis Method Type: Copy number variation analysis in Blood or Tissue by Sequencing
Genomic Study Analysis Method Type: Sequence analysis of select exons
status: Completed
note: alpha-1 antitrypsin deficiency - SERPINA1. Autosomal recessive inheritance. sequencing with copy number analysis. Detection rate: Northern European >99%, No disease-causing mutations were detected in any other gene tested for alpha-1 antitrypsin deficiency, Report content approved by PractitionerJane Smith, PhD, FACMG, CGMB on Jul 9, 2024, Report content approved by Krista Moyer, MGC on Jul 9, 2024
Entry 14 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalGenomicStudyAnalysisFamilialHyperinsulinismPatientMale
Resource Procedure:
Generated Narrative: Procedure PrenatalGenomicStudyAnalysisFamilialHyperinsulinismPatientMale
version: 1; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
Profile: Genomic Study Analysis
org/fhir/uv/genomics-reporting/StructureDefinition/genomic-study-analysis-genomic-source-class: Germline
Genomic Study Analysis Genome Build: GRCh37
Genomic Study Analysis Regions
- description: Exons sequenced
- studied: Exons: NM_000352:1-39
Genomic Study Analysis Regions
- description: Genes studied
- studied: ABCC8
Genomic Study Analysis Method Type: Copy number variation analysis in Blood or Tissue by Sequencing
Genomic Study Analysis Method Type: Sequence analysis of select exons
status: Completed
note: familial hyperinsulinism, ABCC8-related - ABCC8. Autosomal recessive inheritance. sequencing with copy number analysis. Detection rate: Northern European >99%, No disease-causing mutations were detected in any other gene tested for familial hyperinsulinism, ABCC8-related, Report content approved by PractitionerJane Smith, PhD, FACMG, CGMB on Jul 9, 2024, Report content approved by Krista Moyer, MGC on Jul 9, 2024
Entry 15 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalGenomicStudyAnalysisAutosomalRecessiveSAoCSPatientMale
Resource Procedure:
Generated Narrative: Procedure PrenatalGenomicStudyAnalysisAutosomalRecessiveSAoCSPatientMale
version: 1; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
Profile: Genomic Study Analysis
org/fhir/uv/genomics-reporting/StructureDefinition/genomic-study-analysis-genomic-source-class: Germline
Genomic Study Analysis Genome Build: GRCh37
Genomic Study Analysis Regions
- description: Exons sequenced
- studied: Exons: NM_014363:2-10
Genomic Study Analysis Regions
- description: Genes studied
- studied: SACS
Genomic Study Analysis Method Type: Copy number variation analysis in Blood or Tissue by Sequencing
Genomic Study Analysis Method Type: Sequence analysis of select exons
status: Completed
note: autosomal recessive spastic ataxia of Charlevoix-Saguenay - SACS. Autosomal recessive inheritance. sequencing with copy number analysis. Detection rate: Northern European 99%, No disease-causing mutations were detected in any other gene tested for autosomal recessive spastic ataxia of Charlevoix-Saguenay, Report content approved by PractitionerJane Smith, PhD, FACMG, CGMB on Jul 9, 2024, Report content approved by Krista Moyer, MGC on Jul 9, 2024
Entry 16 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalDiagImpAlpha1ADPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalDiagImpAlpha1ADPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Diagnostic Implication
Genomic Risk Assessment: alpha-1 antitrypsin deficiency Residual Risk
status: Final
category: Laboratory, Genetics
code: Diagnostic Implication
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
derivedFrom: Observation Genetic variant assessment
component
code: Associated phenotype
value: Genetic disorder carrier (finding)
component
code: Associated phenotype
value: Alpha-1-antitrypsin deficiency
component
code: Condition Inheritance
value: Autosomal recessive inheritance
Entry 17 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalDiagImpFamilialHyperinsulinismPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalDiagImpFamilialHyperinsulinismPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Diagnostic Implication
Genomic Risk Assessment: familial hyperinsulinism, ABCC8-related Residual Risk
status: Final
category: Laboratory, Genetics
code: Diagnostic Implication
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
derivedFrom: Observation Genetic variant assessment
component
code: Associated phenotype
value: Normal genetic findings (finding)
component
code: Associated phenotype
value: Type 2 diabetes mellitus
component
code: Condition Inheritance
value: Autosomal recessive inheritance
Entry 18 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalDiagImpAutosomalRecessiveSAoCSPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalDiagImpAutosomalRecessiveSAoCSPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Diagnostic Implication
Genomic Risk Assessment: autosomal recessive spastic ataxia of Charlevoix-Saguenay Residual Risk
status: Final
category: Laboratory, Genetics
code: Diagnostic Implication
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
derivedFrom: Observation Genetic variant assessment
component
code: Associated phenotype
value: Normal genetic findings (finding)
component
code: Associated phenotype
value: ARSACS - autosomal recessive spastic ataxia of Charlevoix-Saguenay
component
code: Condition Inheritance
value: Autosomal recessive inheritance
Entry 19 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReprDiagImpAlpha1ADPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalReprDiagImpAlpha1ADPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Diagnostic Implication
Genomic Risk Assessment: alpha-1 antitrypsin deficiency Reproductive Risk
status: Final
category: Laboratory, Genetics
code: Diagnostic Implication
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
note: ## What Is Alpha-1 Antitrypsin Deficiency? Alpha-1 Antitrypsin Deficiency (AATD), caused by mutations in the _SERPINA1_ gene, is an inherited condition that can cause lung and liver disease. The symptoms of AATD vary greatly from individual to individual, even among those in the same family. Knowing which mutations a child inherits can serve as a guide to how severe his or her symptoms might be. The primary mutation that causes symptoms is called the "Z allele." As the name indicates, AATD is caused by a deficiency in a protein called alpha-1 antitrypsin. This protein protects the body from neutrophil elastase, an enzyme which normally fights infection in a helpful way. Without sufficient levels of alpha-1 antitrypsin, neutrophil elastase can attack and harm healthy tissue in the lungs. Abnormally formed alpha-1 antitrypsin can also build up in the liver and cause damage. Ninety-five percent of AATD is caused by the presence of two Z alleles. Individuals who inherit two copies of the Z allele ("ZZ") are most likely to have the severe symptoms of the disease. Smokers with the disease are much more likely to develop symptoms than non-smokers. Secondhand smoke, particularly from one's parents, can also increase the chances of developing symptoms. Emphysema, a chronic disease in which air sacs in the lungs lose their normal ability to expand and contract, is the most common symptom of AATD. Emphysema causes a progressive difficulty in breathing and a hacking cough. It can severely limit physical activity. The first signs of emphysema, shortness of breath and wheezing, often appear between the ages of 40 and 50 in smokers with the disease. Non-smokers with AATD typically develop emphysema symptoms later, even after the age of 60. Liver disease is another possible symptom of AATD. About 2.5% of children with AATD will develop severe liver complications. Common symptoms of these early liver problems include a swollen abdomen, swollen feet or legs, abnormal liver enzyme activity, and a yellowing of the skin or whites of the eyes (jaundice). Overall, 15 to 19% of adults over the age of 50 with two Z alleles develop a build-up of scar tissue in the liver (cirrhosis). This symptom can develop at any age, with a greater risk of cirrhosis later in life. When liver disease associated with AATD begins later in life, destruction of the liver tissue can be rapid. Higher risk for a particular type of liver cancer has been reported among individuals with AATD, notably in men. Individuals with only one copy of the Z allele (called carriers) have a slightly elevated risk for lung or liver problems. One study placed this risk at 8%, versus 2 to 4% for the general population. Smokers who are carriers of the Z allele are more likely to develop lung problems such as emphysema, while non-smoking carriers rarely do. Individuals with AATD may rarely experience inflammation of the skin (panniculitis) or of the blood vessels (vasculitis). These symptoms are much less common than lung or liver complications, with panniculitis estimated to occur in 0.1% and vasculitis estimated to occur in 2% of patients with AATD. ## How Common Is Alpha-1 Antitrypsin Deficiency? In North America, AATD affects 1 in 5,000 to 7,000 individuals. In a study of 75,000 Europeans, researchers estimated that 1 in 4,700 were affected by AATD. The Z allele is most common among individuals of Northwestern European, French Canadian, Cajun, Ashkenazi Jewish, and Middle Eastern ancestry, where up to 1 in 32 individuals are carriers. AATD is rare in Asian and African populations, except in populations that are racially heterogeneous. For example, African-Americans in the United States have a higher rate of AATD than populations in Africa. Researchers believe that AATD is often diagnosed as chronic obstructive pulmonary disease (COPD), a relatively common disease, without the realization that AATD is the cause of the COPD. For this reason, the disease may be more common than prevalence numbers indicate. ## How Is Alpha-1 Antitrypsin Deficiency Treated? Individuals with AATD should not smoke. Smokers are more likely to develop symptoms of AATD. In smokers, symptoms tend to develop at an earlier age and progress at a faster rate. Individuals with the disease should also avoid exposure to secondhand smoke, pollution, mineral dust, gas, and chemical fumes. Regular exercise and good nutrition are beneficial for people with AATD. Carriers of the Z allele should also avoid smoking, as it can increase the risk for health problems related to the Z allele such as COPD or emphysema. Patients who have moderate lung damage are recommended to have infusions of purified human alpha-1 antitrypsin via intravenous injections. This treatment is considered most effective among individuals with moderate lung damage. This type of treatment is not recommended for patients with AATD who have very little or no lung damage. In individuals with severe liver or lung disease, transplantation of the failing organ may be an option. Liver transplants can "cure" the disease, because the donor liver will produce the alpha-1 antitrypsin protein. ## What Is the Prognosis for an Individual with Alpha-1 Antitrypsin Deficiency? The prognosis, or outcome, for patients with AATD depends on the type and severity of symptoms they have. In some patients the disease can shorten lifespan, while in others it allows for a normal lifespan. Roughly 2.5% of children with two copies of the Z allele develop severe liver disease and may need a liver transplant. Overall, smokers show much more severe and rapid lung damage beginning earlier in life than non-smokers, and those with one or more copies of the Z allele are more likely to develop symptoms. In non-smokers who develop lung complications after their 60th birthday, lifespan may be normal., Alpha-1 Antitrypsin Deficiency (AATD) causes lung and liver disease. The condition is primarily an adult-onset condition, and not all people with the condition will develop symptoms. In approximately 2.5% of cases, children with the condition will develop liver complications. People affected by AATD should avoid smoking. In some cases the disease shortens lifespan, while in many others it does not.
derivedFrom: Observation Genetic variant assessment
component
code: Associated phenotype
value: Alpha-1-antitrypsin deficiency
component
code: Condition Inheritance
value: Autosomal recessive inheritance
Entry 20 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReprDiagImpAutosomalRecessiveSAoCSPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalReprDiagImpAutosomalRecessiveSAoCSPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Diagnostic Implication
Genomic Risk Assessment: autosomal recessive spastic ataxia of Charlevoix-Saguenay Reproductive Risk
status: Final
category: Laboratory, Genetics
code: Diagnostic Implication
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
note: ## What Is Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay? Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a progressive inherited condition that affects the body's ability to create a protein called sacsin, normally found in the brain, skin, and muscles. ARSACS is caused by mutations in the _SACS_ gene. The first symptom, unsteady gait, typically appears between 12 and 18 months of age, as toddlers begin to walk. Children also develop speech problems due to weak neck and facial muscles. The condition becomes increasingly worse over time, with muscle tension and spasms, difficulty coordinating movements, involuntary eye movements, and muscle wasting. Some people with ARSACS also lose sensation in their arms and legs as the nerves degenerate. Other symptoms include incontinence, deformities of the fingers and feet, and buildup of fatty tissue on the retina leading to vision problems. Occasionally, the disease also causes leaks in one of the valves that control blood flow through the heart. Most people with the condition are of normal intelligence and are able to live independently well into adulthood, although they eventually lose the ability to walk. ## How Common Is Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay? The majority of people with ARSACS have ancestry in the Charlevoix-Saguenay region of Quebec, Canada, where the condition affects approximately 1 in 1,500 to 2,000 people. While patients with ARSACS have been reported in other populations, the worldwide incidence is unknown. ## How Is Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Treated? There is no cure for ARSACS. Treatment focuses on easing the symptoms and postponing major functional disabilities. Physical therapy and anti-spasmodic oral medications can help control muscle spasms, prevent joint and tendon deformities, and preserve muscle function for some time. Low doses of medication can control incontinence. Occupational therapy and adaptive tools such as leg braces can support people with ARSACS in daily tasks such as driving. As the disease progresses, however, people with ARSACS typically lose the ability to perform these tasks. Children with the condition may benefit from speech therapy and other forms of support in school. ## What Is the Prognosis for a Person with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay? People with ARSACS become wheelchair-bound at an average age of 41 and commonly die in their fifties., Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) affects muscle movement. It causes abnormal tensing of the muscles, difficulty with coordination, muscle wasting, involuntary eye movements, and speech difficulties. The symptoms can begin as early as 12 to 18 months of age and become increasingly worse over time. Most people with the condition require a wheelchair in adulthood and die in their fifties.
derivedFrom: Observation Genetic variant assessment
component
code: Associated phenotype
value: ARSACS - autosomal recessive spastic ataxia of Charlevoix-Saguenay
component
code: Condition Inheritance
value: Autosomal recessive inheritance
Entry 21 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReprDiagImpFamilialHyperinsulinismPatientMale
Resource Observation:
Generated Narrative: Observation PrenatalReprDiagImpFamilialHyperinsulinismPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Diagnostic Implication
Genomic Risk Assessment: familial hyperinsulinism, ABCC8-related Reproductive Risk
status: Final
category: Laboratory, Genetics
code: Diagnostic Implication
effective: 2024-07-09
performer: Practitioner PractitionerJane Smith
note: ##What is Familial Hyperinsulinism, ABCC8-related? Familial hyperinsulinism, ABCC8-related is an inherited condition that causes low blood sugar levels (hypoglycemia). In a healthy individual, the pancreas secretes a hormone called insulin after eating carbohydrates in response to rising blood sugar. In familial hyperinsulinism, insulin is secreted even without carbohydrate consumption. An excess of insulin released into the blood can cause blood sugars to drop to dangerously low levels. Familial hyperinsulinism, ABCC8-related is caused by harmful genetic changes (mutations) in the _ABCC8_ gene. Infants with familial hyperinsulinism tend to have very low blood sugar within the first few days of life. These newborns are typically larger at birth and may have difficulty feeding, poor muscle tone, and breathing problems. These infants often require immediate infusions of glucose to help raise blood sugar levels and prevent seizures. Prolonged hypoglycemia can also lead to permanent brain damage. In some individuals with familial hyperinsulinism, symptoms do not appear until later in childhood. The low blood sugar associated with the condition can also range from mild to severe depending on the individual, and it can vary even among members of the same family. There are two forms of familial hyperinsulism: the diffuse form and the focal form, each inherited in a different manner. ###Diffuse form In the diffuse form of the disease, all insulin-producing cells in the pancreas are affected. The diffuse form is typically inherited in an autosomal-recessive manner (i.e., two mutations are needed to cause the condition). In approximately 10 to 20% of cases, it is inherited an autosomal-dominant manner (i.e., only one mutation is needed to cause the condition), in which case carriers may be at risk for symptoms of hyperinsulism. ###Focal form In the focal form of the disease, only some of the insulin-producing cells of the pancreas are affected. For a child to have this form of the disease, two separate events must occur. The first is the inheritance of an _ABCC8_ mutation from their father. The second is that during fetal development a spontaneous mutation must arise in their other copy of the _ABCC8_ gene. This spontaneous mutation will only occur in some of the cells, which explains the focal nature. Male carriers have a 1 in 1,200 risk of having a child affected with focal hyperinsulism. ###Additional findings Specific mutations in the _ABCC8_ gene cause neonatal diabetes. In neonatal diabetes, not enough insulin is secreted, and blood sugar increases to dangerously high levels (hyperglycemia). Infants with neonatal diabetes tend to have high blood sugar levels between birth and six months of age. These newborns are typically smaller at birth and may have difficulty feeding, severe dehydration, glucose in the urine, and excessive urination. While some with neonatal diabetes need lifelong treatment to prevent high blood sugar, others may not experience symptoms after a few weeks or months. In rare cases, some infants may also have neurological symptoms, which can include developmental delay, muscle weakness, and seizures. As in familial hyperinsulinism, symptoms of neonatal diabetes can range from mild to severe, and severity can vary among family members. In most cases, neonatal diabetes caused by _ABCC8_ is inherited in an autosomal-dominant manner. Carriers may be at risk for diabetes. ##How common is Familial Hyperinsulinism, ABCC8-related? Several genes are known to cause familial hyperinsulinism, with _ABCC8_ mutations accounting for approximately 45% of documented cases. The overall incidence of hyperinsulinism is approximately 1 in 50,000 individuals. The incidence of familial hyperinsulinism, ABCC8-related may be more common among individuals of Ashkenazi Jewish descent. ##How is Familial Hyperinsulinism, ABCC8-related treated? Treatment for familial hyperinsulinism includes a special diet, medications, and surgical intervention. If an infant shows symptoms of familial hyperinsulinism at birth, glucose is often given through a vein (intravenously) to raise and stabilize the blood sugar level. Infants may also need frequent feedings with large amounts of carbohydrates, even overnight. A feeding tube may be helpful to ensure that an infant receives sufficient quantities of carbohydrates. There are also several types of medications that manage familial hyperinsulinism. Most of these medications focus on reducing the amount of insulin that is released into the body. Surgery may be needed to remove part of the pancreas if diet and medication cannot sufficiently manage a patient's blood sugar levels. After an extended period of successful treatment, many with familial hyperinsulinism find that their symptoms become less severe or even go into remission. However, individuals with familial hyperinsulinism may find their symptoms get worse if they have a viral infections. Such individuals should manage their symptoms carefully if they become ill, even if their symptoms have gone into remission. They should also avoid long periods of time without eating. ##What is the prognosis for an individual with Familial Hyperinsulinism, ABCC8-related? The long-term outlook for an individual with familial hyperinsulinism depends upon the severity of the symptoms and how well individuals respond to treatment. Permanent brain damage can occur from episodes of low blood sugar. Even with treatment, those with the disease can develop some degree of brain damage or have learning difficulties. They also may be at an elevated risk of diabetes. In the most serious cases, when the disease is not recognized and properly treated, it can be fatal. With early diagnosis and careful treatment, individuals with familial hyperinsulinism can have normal lifespans., Familial hyperinsulinism, ABCC8-related is an inherited condition in which the pancreas releases too much insulin, leading to dangerously low blood sugar levels (hypoglycemia). Seizures and permanent brain damage may occur as a result. In rare cases, mutations in this gene cause neonatal diabetes, where not enough insulin is produced, leading to high blood sugar (hyperglycemia) and, in rare cases, neurological symptoms. With early diagnosis and careful treatment using a combination of dietary modification, medications, and/or surgery, people with familial hyperinsulinism or neonatal diabetes can often have a normal lifespan.
derivedFrom: Observation Genetic variant assessment
component
code: Associated phenotype
value: Type 2 diabetes mellitus
component
code: Condition Inheritance
value: Autosomal recessive inheritance
Entry 22 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalSpecimenPatientMale
Resource Specimen:
Generated Narrative: Specimen PrenatalSpecimenPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
identifier:
http://www.somesystemabc.net/identifiers/specimens/55200000000223status: Available
type: Saliva specimen (specimen)
receivedTime: 2024-07-09 19:38:50+0000
Collections
Collected[x] 2024-07-04 00:00:00+0000
Entry 23 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/Organization
Resource Organization:
Generated Narrative: Organization Organization
identifier: Clinical Laboratory Improvement Amendments/12A4567890 (use: official, )
type: Healthcare Provider
name: Generic Laboratories, Inc.
contact
telecom: ph: (800) 876-5309, fax: (781) 876-5305, http://www.genericlaboratoriesinc.com, info@genericlaboratoriesinc.com
address: 321 Laboratory Court, Anytown, MA, 12345, USA
Entry 24 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalServiceRequestPatientMale
Resource ServiceRequest:
Generated Narrative: ServiceRequest PrenatalServiceRequestPatientMale
identifier: Laboratory Accession ID/GNV3VZQYKRPC
status: Active
intent: Order
code: No display for ServiceRequest.code (concept: Prenatal Test)
requester: Practitioner Laura Salma
Entry 25 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalRecommendedFollowup2PatientMale
Resource Task:
Generated Narrative: Task PrenatalRecommendedFollowup2PatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Followup Recommendation
status: Requested
intent: Proposal
code: Genetic counseling recommended
description: Patients are recommended to discuss reproductive risks with their health care provider or a genetic counselor. Patients may also wish to discuss any positive results with blood relatives, as there is an increased chance that they are also carriers.
Entry 26 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalRecommendedFollowup1PatientMale
Resource Task:
Generated Narrative: Task PrenatalRecommendedFollowup1PatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
Profile: Followup Recommendation
status: Requested
intent: Proposal
code: Genetic counseling recommended
description: Carrier testing should be considered for the diseases specified above for the patient's partner.
Entry 27 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalGenomicStudyPatientMale
Resource Procedure:
Generated Narrative: Procedure PrenatalGenomicStudyPatientMale
version: 2; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
Profile: Genomic Study
status: Completed
category: Laboratory
note: The <b>Organization Prenatal Carrier Screen</b> utilizes sequencing, maximizing coverage across all DNA regions tested, to help you learn about your chance to have a child with a genetic disease.
Entry 28 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReproductivePreRiskFamilialHyperinsulinismPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalReproductivePreRiskFamilialHyperinsulinismPatientMale
version: 2; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
status: Final
occurrence: 2024-07-09
basis:
- RiskAssessment: status = final; occurrence[x] = 2024-07-09
- Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Predictions
Outcome Probability[x] Risk for inheriting a disease-causing mutation for familial hyperinsulinism, ABCC8-related before Prenatal test 0.000008508465923593976 note: Residual risk is an estimate of each patient's post- test likelihood of being a carrier, while the reproductive risk represents an estimated likelihood that the patients' future children could inherit each disease. These risks are inherent to all carrier-screening tests, may vary by ethnicity, are predicated on a negative family history, and are present even given a negative test result. Inaccurate reporting of ethnicity may cause errors in risk calculation. In addition, average carrier rates are estimated using incidence or prevalence data from published scientific literature and/or reputable databases, where available, and are incorporated into residual risk calculations for each population/ethnicity. When population-specific data is not available for a condition, average worldwide incidence or prevalence is used. Further, incidence and prevalence data are only collected for the specified phenotypes (which include primarily the classic or severe forms of disease) and may not include alternate or milder disease manifestations associated with the gene. Actual incidence rates, prevalence rates, and carrier rates, and therefore actual residual risks, may be higher or lower than the estimates provided. Carrier rates, incidence/prevalence, and/or residual risks are not provided for some genes with biological or heritable properties that would make these estimates inaccurate. See the full clinical report for interpretation and details. The reproductive risk presented is based on a hypothetical pairing with a partner of the same ethnic group.
Entry 29 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReproductivePreRiskAlpha1ADPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalReproductivePreRiskAlpha1ADPatientMale
version: 2; Last updated: 2024-10-02 03:41:29+0000;
Information Source: #DEqMJP5Koyub2naR
status: Final
occurrence: 2024-07-09
basis:
- RiskAssessment: status = final; occurrence[x] = 2024-07-09
- Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Predictions
Outcome Probability[x] Risk for inheriting a disease-causing mutation for alpha-1 antitrypsin deficiency before Prenatal test 0.0003310162197947699 note: Residual risk is an estimate of each patient's post- test likelihood of being a carrier, while the reproductive risk represents an estimated likelihood that the patients' future children could inherit each disease. These risks are inherent to all carrier-screening tests, may vary by ethnicity, are predicated on a negative family history, and are present even given a negative test result. Inaccurate reporting of ethnicity may cause errors in risk calculation. In addition, average carrier rates are estimated using incidence or prevalence data from published scientific literature and/or reputable databases, where available, and are incorporated into residual risk calculations for each population/ethnicity. When population-specific data is not available for a condition, average worldwide incidence or prevalence is used. Further, incidence and prevalence data are only collected for the specified phenotypes (which include primarily the classic or severe forms of disease) and may not include alternate or milder disease manifestations associated with the gene. Actual incidence rates, prevalence rates, and carrier rates, and therefore actual residual risks, may be higher or lower than the estimates provided. Carrier rates, incidence/prevalence, and/or residual risks are not provided for some genes with biological or heritable properties that would make these estimates inaccurate. See the full clinical report for interpretation and details. The reproductive risk presented is based on a hypothetical pairing with a partner of the same ethnic group.
Entry 30 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalReproductivePreRiskAutosomalRecessiveSAoCSPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalReproductivePreRiskAutosomalRecessiveSAoCSPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
status: Final
occurrence: 2024-07-09
basis:
- RiskAssessment: status = final; occurrence[x] = 2024-07-09
- Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, ))
Predictions
Outcome Probability[x] Risk for inheriting a disease-causing mutation for autosomal recessive spastic ataxia of Charlevoix-Saguenay before Prenatal test 0.000001 note: Residual risk is an estimate of each patient's post- test likelihood of being a carrier, while the reproductive risk represents an estimated likelihood that the patients' future children could inherit each disease. These risks are inherent to all carrier-screening tests, may vary by ethnicity, are predicated on a negative family history, and are present even given a negative test result. Inaccurate reporting of ethnicity may cause errors in risk calculation. In addition, average carrier rates are estimated using incidence or prevalence data from published scientific literature and/or reputable databases, where available, and are incorporated into residual risk calculations for each population/ethnicity. When population-specific data is not available for a condition, average worldwide incidence or prevalence is used. Further, incidence and prevalence data are only collected for the specified phenotypes (which include primarily the classic or severe forms of disease) and may not include alternate or milder disease manifestations associated with the gene. Actual incidence rates, prevalence rates, and carrier rates, and therefore actual residual risks, may be higher or lower than the estimates provided. Carrier rates, incidence/prevalence, and/or residual risks are not provided for some genes with biological or heritable properties that would make these estimates inaccurate. See the full clinical report for interpretation and details. The reproductive risk presented is based on a hypothetical pairing with a partner of the same ethnic group.
Entry 31 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalNegativeReprRiskPatientMale
Resource RiskAssessment:
Generated Narrative: RiskAssessment PrenatalNegativeReprRiskPatientMale
version: 1; Last updated: 2024-09-25 00:01:34+0000;
Information Source: #hrQE3dHjuHuJ5zkf
status: Final
occurrence: 2024-07-09
Entry 32 - fullUrl = http://hapi-fhir-server:8080/fhir/Bundle/PrenatalGenomicReportPatientMale
Resource DiagnosticReport:
Generated Narrative: DiagnosticReport PrenatalGenomicReportPatientMale
Genetic analysis report (Genetics)
Subject Higado Sobreviviente (official) Male, DoB: 1996-05-13 ( Patient ID: fec6172efdca41b4a13341e75cb62e0f (use: official, )) When For 2024-07-09 Performers Organization Generic Laboratories, Inc. Practitioner PractitionerJane Smith Report Details
Code Value Flags Note Genetic variant assessment Absent Final Genetic variant assessment Absent Final Genetic variant assessment Present Final Diagnostic Implication Final ##What is Familial Hyperinsulinism, ABCC8-related? Familial hyperinsulinism, ABCC8-related is an inherited condition that causes low blood sugar levels (hypoglycemia). In a healthy individual, the pancreas secretes a hormone called insulin after eating carbohydrates in response to rising blood sugar. In familial hyperinsulinism, insulin is secreted even without carbohydrate consumption. An excess of insulin released into the blood can cause blood sugars to drop to dangerously low levels. Familial hyperinsulinism, ABCC8-related is caused by harmful genetic changes (mutations) in the _ABCC8_ gene. Infants with familial hyperinsulinism tend to have very low blood sugar within the first few days of life. These newborns are typically larger at birth and may have difficulty feeding, poor muscle tone, and breathing problems. These infants often require immediate infusions of glucose to help raise blood sugar levels and prevent seizures. Prolonged hypoglycemia can also lead to permanent brain damage. In some individuals with familial hyperinsulinism, symptoms do not appear until later in childhood. The low blood sugar associated with the condition can also range from mild to severe depending on the individual, and it can vary even among members of the same family. There are two forms of familial hyperinsulism: the diffuse form and the focal form, each inherited in a different manner. ###Diffuse form In the diffuse form of the disease, all insulin-producing cells in the pancreas are affected. The diffuse form is typically inherited in an autosomal-recessive manner (i.e., two mutations are needed to cause the condition). In approximately 10 to 20% of cases, it is inherited an autosomal-dominant manner (i.e., only one mutation is needed to cause the condition), in which case carriers may be at risk for symptoms of hyperinsulism. ###Focal form In the focal form of the disease, only some of the insulin-producing cells of the pancreas are affected. For a child to have this form of the disease, two separate events must occur. The first is the inheritance of an _ABCC8_ mutation from their father. The second is that during fetal development a spontaneous mutation must arise in their other copy of the _ABCC8_ gene. This spontaneous mutation will only occur in some of the cells, which explains the focal nature. Male carriers have a 1 in 1,200 risk of having a child affected with focal hyperinsulism. ###Additional findings Specific mutations in the _ABCC8_ gene cause neonatal diabetes. In neonatal diabetes, not enough insulin is secreted, and blood sugar increases to dangerously high levels (hyperglycemia). Infants with neonatal diabetes tend to have high blood sugar levels between birth and six months of age. These newborns are typically smaller at birth and may have difficulty feeding, severe dehydration, glucose in the urine, and excessive urination. While some with neonatal diabetes need lifelong treatment to prevent high blood sugar, others may not experience symptoms after a few weeks or months. In rare cases, some infants may also have neurological symptoms, which can include developmental delay, muscle weakness, and seizures. As in familial hyperinsulinism, symptoms of neonatal diabetes can range from mild to severe, and severity can vary among family members. In most cases, neonatal diabetes caused by _ABCC8_ is inherited in an autosomal-dominant manner. Carriers may be at risk for diabetes. ##How common is Familial Hyperinsulinism, ABCC8-related? Several genes are known to cause familial hyperinsulinism, with _ABCC8_ mutations accounting for approximately 45% of documented cases. The overall incidence of hyperinsulinism is approximately 1 in 50,000 individuals. The incidence of familial hyperinsulinism, ABCC8-related may be more common among individuals of Ashkenazi Jewish descent. ##How is Familial Hyperinsulinism, ABCC8-related treated? Treatment for familial hyperinsulinism includes a special diet, medications, and surgical intervention. If an infant shows symptoms of familial hyperinsulinism at birth, glucose is often given through a vein (intravenously) to raise and stabilize the blood sugar level. Infants may also need frequent feedings with large amounts of carbohydrates, even overnight. A feeding tube may be helpful to ensure that an infant receives sufficient quantities of carbohydrates. There are also several types of medications that manage familial hyperinsulinism. Most of these medications focus on reducing the amount of insulin that is released into the body. Surgery may be needed to remove part of the pancreas if diet and medication cannot sufficiently manage a patient's blood sugar levels. After an extended period of successful treatment, many with familial hyperinsulinism find that their symptoms become less severe or even go into remission. However, individuals with familial hyperinsulinism may find their symptoms get worse if they have a viral infections. Such individuals should manage their symptoms carefully if they become ill, even if their symptoms have gone into remission. They should also avoid long periods of time without eating. ##What is the prognosis for an individual with Familial Hyperinsulinism, ABCC8-related? The long-term outlook for an individual with familial hyperinsulinism depends upon the severity of the symptoms and how well individuals respond to treatment. Permanent brain damage can occur from episodes of low blood sugar. Even with treatment, those with the disease can develop some degree of brain damage or have learning difficulties. They also may be at an elevated risk of diabetes. In the most serious cases, when the disease is not recognized and properly treated, it can be fatal. With early diagnosis and careful treatment, individuals with familial hyperinsulinism can have normal lifespans., Familial hyperinsulinism, ABCC8-related is an inherited condition in which the pancreas releases too much insulin, leading to dangerously low blood sugar levels (hypoglycemia). Seizures and permanent brain damage may occur as a result. In rare cases, mutations in this gene cause neonatal diabetes, where not enough insulin is produced, leading to high blood sugar (hyperglycemia) and, in rare cases, neurological symptoms. With early diagnosis and careful treatment using a combination of dietary modification, medications, and/or surgery, people with familial hyperinsulinism or neonatal diabetes can often have a normal lifespan. Diagnostic Implication Final ## What Is Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay? Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a progressive inherited condition that affects the body's ability to create a protein called sacsin, normally found in the brain, skin, and muscles. ARSACS is caused by mutations in the _SACS_ gene. The first symptom, unsteady gait, typically appears between 12 and 18 months of age, as toddlers begin to walk. Children also develop speech problems due to weak neck and facial muscles. The condition becomes increasingly worse over time, with muscle tension and spasms, difficulty coordinating movements, involuntary eye movements, and muscle wasting. Some people with ARSACS also lose sensation in their arms and legs as the nerves degenerate. Other symptoms include incontinence, deformities of the fingers and feet, and buildup of fatty tissue on the retina leading to vision problems. Occasionally, the disease also causes leaks in one of the valves that control blood flow through the heart. Most people with the condition are of normal intelligence and are able to live independently well into adulthood, although they eventually lose the ability to walk. ## How Common Is Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay? The majority of people with ARSACS have ancestry in the Charlevoix-Saguenay region of Quebec, Canada, where the condition affects approximately 1 in 1,500 to 2,000 people. While patients with ARSACS have been reported in other populations, the worldwide incidence is unknown. ## How Is Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay Treated? There is no cure for ARSACS. Treatment focuses on easing the symptoms and postponing major functional disabilities. Physical therapy and anti-spasmodic oral medications can help control muscle spasms, prevent joint and tendon deformities, and preserve muscle function for some time. Low doses of medication can control incontinence. Occupational therapy and adaptive tools such as leg braces can support people with ARSACS in daily tasks such as driving. As the disease progresses, however, people with ARSACS typically lose the ability to perform these tasks. Children with the condition may benefit from speech therapy and other forms of support in school. ## What Is the Prognosis for a Person with Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay? People with ARSACS become wheelchair-bound at an average age of 41 and commonly die in their fifties., Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) affects muscle movement. It causes abnormal tensing of the muscles, difficulty with coordination, muscle wasting, involuntary eye movements, and speech difficulties. The symptoms can begin as early as 12 to 18 months of age and become increasingly worse over time. Most people with the condition require a wheelchair in adulthood and die in their fifties. Diagnostic Implication Final ## What Is Alpha-1 Antitrypsin Deficiency? Alpha-1 Antitrypsin Deficiency (AATD), caused by mutations in the _SERPINA1_ gene, is an inherited condition that can cause lung and liver disease. The symptoms of AATD vary greatly from individual to individual, even among those in the same family. Knowing which mutations a child inherits can serve as a guide to how severe his or her symptoms might be. The primary mutation that causes symptoms is called the "Z allele." As the name indicates, AATD is caused by a deficiency in a protein called alpha-1 antitrypsin. This protein protects the body from neutrophil elastase, an enzyme which normally fights infection in a helpful way. Without sufficient levels of alpha-1 antitrypsin, neutrophil elastase can attack and harm healthy tissue in the lungs. Abnormally formed alpha-1 antitrypsin can also build up in the liver and cause damage. Ninety-five percent of AATD is caused by the presence of two Z alleles. Individuals who inherit two copies of the Z allele ("ZZ") are most likely to have the severe symptoms of the disease. Smokers with the disease are much more likely to develop symptoms than non-smokers. Secondhand smoke, particularly from one's parents, can also increase the chances of developing symptoms. Emphysema, a chronic disease in which air sacs in the lungs lose their normal ability to expand and contract, is the most common symptom of AATD. Emphysema causes a progressive difficulty in breathing and a hacking cough. It can severely limit physical activity. The first signs of emphysema, shortness of breath and wheezing, often appear between the ages of 40 and 50 in smokers with the disease. Non-smokers with AATD typically develop emphysema symptoms later, even after the age of 60. Liver disease is another possible symptom of AATD. About 2.5% of children with AATD will develop severe liver complications. Common symptoms of these early liver problems include a swollen abdomen, swollen feet or legs, abnormal liver enzyme activity, and a yellowing of the skin or whites of the eyes (jaundice). Overall, 15 to 19% of adults over the age of 50 with two Z alleles develop a build-up of scar tissue in the liver (cirrhosis). This symptom can develop at any age, with a greater risk of cirrhosis later in life. When liver disease associated with AATD begins later in life, destruction of the liver tissue can be rapid. Higher risk for a particular type of liver cancer has been reported among individuals with AATD, notably in men. Individuals with only one copy of the Z allele (called carriers) have a slightly elevated risk for lung or liver problems. One study placed this risk at 8%, versus 2 to 4% for the general population. Smokers who are carriers of the Z allele are more likely to develop lung problems such as emphysema, while non-smoking carriers rarely do. Individuals with AATD may rarely experience inflammation of the skin (panniculitis) or of the blood vessels (vasculitis). These symptoms are much less common than lung or liver complications, with panniculitis estimated to occur in 0.1% and vasculitis estimated to occur in 2% of patients with AATD. ## How Common Is Alpha-1 Antitrypsin Deficiency? In North America, AATD affects 1 in 5,000 to 7,000 individuals. In a study of 75,000 Europeans, researchers estimated that 1 in 4,700 were affected by AATD. The Z allele is most common among individuals of Northwestern European, French Canadian, Cajun, Ashkenazi Jewish, and Middle Eastern ancestry, where up to 1 in 32 individuals are carriers. AATD is rare in Asian and African populations, except in populations that are racially heterogeneous. For example, African-Americans in the United States have a higher rate of AATD than populations in Africa. Researchers believe that AATD is often diagnosed as chronic obstructive pulmonary disease (COPD), a relatively common disease, without the realization that AATD is the cause of the COPD. For this reason, the disease may be more common than prevalence numbers indicate. ## How Is Alpha-1 Antitrypsin Deficiency Treated? Individuals with AATD should not smoke. Smokers are more likely to develop symptoms of AATD. In smokers, symptoms tend to develop at an earlier age and progress at a faster rate. Individuals with the disease should also avoid exposure to secondhand smoke, pollution, mineral dust, gas, and chemical fumes. Regular exercise and good nutrition are beneficial for people with AATD. Carriers of the Z allele should also avoid smoking, as it can increase the risk for health problems related to the Z allele such as COPD or emphysema. Patients who have moderate lung damage are recommended to have infusions of purified human alpha-1 antitrypsin via intravenous injections. This treatment is considered most effective among individuals with moderate lung damage. This type of treatment is not recommended for patients with AATD who have very little or no lung damage. In individuals with severe liver or lung disease, transplantation of the failing organ may be an option. Liver transplants can "cure" the disease, because the donor liver will produce the alpha-1 antitrypsin protein. ## What Is the Prognosis for an Individual with Alpha-1 Antitrypsin Deficiency? The prognosis, or outcome, for patients with AATD depends on the type and severity of symptoms they have. In some patients the disease can shorten lifespan, while in others it allows for a normal lifespan. Roughly 2.5% of children with two copies of the Z allele develop severe liver disease and may need a liver transplant. Overall, smokers show much more severe and rapid lung damage beginning earlier in life than non-smokers, and those with one or more copies of the Z allele are more likely to develop symptoms. In non-smokers who develop lung complications after their 60th birthday, lifespan may be normal., Alpha-1 Antitrypsin Deficiency (AATD) causes lung and liver disease. The condition is primarily an adult-onset condition, and not all people with the condition will develop symptoms. In approximately 2.5% of cases, children with the condition will develop liver complications. People affected by AATD should avoid smoking. In some cases the disease shortens lifespan, while in many others it does not. Diagnostic Implication Final Diagnostic Implication Final Diagnostic Implication Final Subject's offspring are at increased risk for inheriting the following genetic diseases: , and alpha-1 antitrypsin deficiency
Coded Conclusions:
- Positive