Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency.
Incidence
Autosomal recessive.
Clinical Characteristics
In 3 daughters of Tunisian parents who were not known to be related but came from the same village in Tunisia, Labrune et al. (1990) described hypermethioninemia associated with failure to thrive, mental and motor retardation, facial dysmorphism with abnormal hair and teeth, and myocardiopathy. Hepatic S-adenosylhomocysteine hydrolase activity was decreased by 80% in the 3 children. Neonatal cholestasis was also a feature. A fourth daughter, who died of hepatic failure at the age of 9 months, was probably also affected. The disorder was presumably autosomal recessive. Baric et al. (2004) described a Croatian boy with S-adenosylhomocysteine hydrolase deficiency. Psychomotor development was slow until his fifth month and was virtually absent thereafter, until treatment was started (not described). He had marked hypotonia, elevated serum creatine kinase and transaminases, prolonged prothrombin time, and low albumin. Electron microscopy of muscle showed numerous abnormal myelin figures; liver biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. At age 12 months, brain MRI showed white matter atrophy and abnormally slow myelination. Hypermethioninemia was present in the initial metabolic study at age 8 months, and persisted (up to 784 microM) without tyrosine elevation. Plasma total homocysteine was very slightly elevated for an infant. Activity of S-adenosylhomocysteine hydrolase was approximately 3% of control in liver and was 5 to 10% of the control values in red blood cells and cultured fibroblasts. Causes of hypermethioninemia include hereditary tyrosinemia, cystathionine beta-synthase deficiency, and methionine adenosyltransferase deficiency.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
EB-L, EB-R, EB-F. Activity of S-adenosylhomocysteine hydrolase was approximately 3% of control in liver and was 5 to 10% of the control values in red blood cells and cultured fibroblasts. Placental S-adenosylhomocysteine hydrolase deficiency. Aminoacids in plasma quantitative.