The disease presents with findings that can range from multiple organ disease beginning in infancy or early childhood to only thromboembolism expressed in early to middle adult years. The major findings in classic homocystinuria include developmental delay and mental retardation, ectopia lentis and/or severe myopia, skeletal abnormalities, vascular abnormalities such as thromboembolism, and clinical similarities to Marfan syndrome. Expressivity is variable for all of the clinical signs. Two phenotypic variants are recognized, B6-responsive homocystinuria and B6-non-responsive homocystinuria. B6-responsive homocystinuria is typically, but not always, milder than the non-responsive variant. The mean IQ of affected individuals with B6-responsiveness is 79 versus 57 for those who are B6 non responsive. Thromboembolism is the major cause of early death and morbidity. Other features that may occur include seizures, psychiatric problems, extrapyramidal signs such as dystonia, hypopigmentation, pancreatitis, malar flush, and livedo reticularis.
Homocystinuria is caused by mutations in the CBS gene (21q22.3). Sequencing of the CBS gene is recommended after a biochemical diagnosis of homocystinuria, and provides a complementary method to confirm the presence of mutations in a proband, identify carriers among the proband's relatives, and provide prenatal diagnosis in families with known mutations.
- Confirmation of a clinical/biochemical diagnosis of homocystinuria
- Carrier testing in adults with a family history of homocystinuria
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Plasma Amino Acid Analysis (AA) and Urine Amino Acid Analysis (UA) are used in the diagnosis of a patient with homocystinuria.
- Custom Diagnostic Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
- Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor before collecting a fetal sample.