Homocystinuria (CBS Deficiency)
Differential Diagnosis: Classical Homocystinuria (cystathionine β-synthase (CBS) deficiency); hypermethioninemia, due to MATI/III deficiency; GAMT deficiency; adenosylhomocysteine hydrolase deficiency; liver disease; hyperalimentation.
Condition Description: Methionine from ingested protein is normally converted to homocysteine. In classical Homocystinuria due to CBS deficiency, homocysteine can not be converted to cystathionine. As a result, the concentration of homocysteine and its precursor, Methionine, will become elevated. In MAT I/III deficiency and the other hypermethioninemias, methionine is increased in the absence of or only with a slightly increased level of homocysteine.
YOU SHOULD TAKE THE FOLLOWING IMMEDIATE ACTIONS:
- Contact family to inform them of the newborn screening result and ascertain clinical status
- Consult with pediatric metabolic specialist
- Evaluate the newborn with attention to liver disease and refer as appropriate
- Initiate timely confirmatory/diagnostic tests in consultation with metabolic specialist
- Educate family about Homocystinuria and its management, as appropriate
- Report findings to state newborn screening program (Carleigh Soule at 307-777-6297)
Diagnostic Evaluation: Quantitative plasma amino acids will show increased homocysteine and methionine in classical Homocystinuria but only increased methionine in the other disorders. Plasma homocysteine analysis will show markedly increased homocysteine in classical Homocystinuria and normal or only slightly increased homocysteine in the other disorders. Urine homocysteine is markedly increased in classical homocystinuria.
Clinical Considerations: Homocystinuria is usually asymptomatic in the neonate. If untreated, these children eventually develop mental retardation, ectopia lentis, a marfanoid appearance, including arachnodactyly, osteoporosis, other skeletal deformities and thromboembolism. MAT I/III deficiency may be benign. Adenosylhomocysteine hydrolase deficiency has been associated with developmental delay and hypotonia and both this disorder and GAMT deficiency can cause liver abnormalities.
Additional Information: (Click on the name to take you to the website)
Genetic Home Reference Wyoming Department of Health
Gene Tests – Gene Clinics Colorado Newborn Screening
New England Consortium American Academy of Pediatrics
For Algorithm: http://www.acmg.net/resources/policies/ACT/Visio-Methionine-(4-18-06).pdf