Methionineadenosyltransferase deficiency | Neurological symptoms and demyelination possible | Isolated hypermethioninemia, low S-adenosylmethionine, mild hyperhomocysteinemia | AR, MAT1A gene on 10q22 | Analysis of amino acids, total homocysteine, and SAM in plasma;
mutational testing | SAM supplementation in symptomatic individuals |
Methionine synthase and MS reductase deficiency | Dysmyelination, retinopathy, megaloblastic anemia, mental
retardation | Hyperhomocysteinemia due to defective remethylation, methylfolate trapping | AR, MTR gene (1q43) or MTRR gene (5p15.3-15.2) | Amino acids and total homocysteine in plasma, enzyme analysis,
complementation analysis, or mutation testing | Supplementation of cobalamin, betaine, and possibly methionine |
S-adenosylhomocysteine hydrolase deficiency | Hepatitis with neonatal cholestasis, poor synthetic liver function,
(cardio)myopathy, mental retardation | Mild hyperhomocysteinemia, gross elevation of SAH, mild increase
of methionine and SAM | AR, AHCY gene on 20cen-q13.1 | Analysis of amino acids, total homocysteine, SAM and SAH
in plasma, enzyme assay, mutation testing | Supplementation with creatine and phosphatidylcholine. Methionine restriction |
Cystathioninuria (cystathionase deficiency) | Asymptomatic | Accumulation of cystathionine in plasma and urine | AR, CTH gene on 1p31.1 | Analysis of plasma or urinary amino acid analysis, plasma
total homocysteine | No specific treatment |
Molybdenum cofactor deficiency | Early intractable epilepsy, kidney stones | Combined defect of sulfite oxidase, xanthine dehydrogenase,
and aldehyde oxidase | AR, three genes involved: MOCS1 (6p21.3), MOCS2 (5q11), and
GEPH (14q24) | Urinary sulfite and xanthine excretion, decreased urate in plasma,
enzyme assay, mutation testing | No specific treatment |
Gamma- glutamylcysteine synthetase deficiency | Hematolytic anemia, neurological symptoms possible | Low glutathione and gamma-glutamylcysteine in erythrocytes | AR, two genes for two subunits, GCLM gene on 1p.22.1 and
GCLC gene on 6p12 | Measurement of glutathione and gamma-glutamylcysteine, enzyme
assay, mutation analysis | Avoidance of drugs known to induce hemolysis in glucose-6-P
dehydrogenase |
Glutathionuria (gamma-glutamyl transpeptidase deficiency) | Mental retardation or seizures possible | Increased glutathione in plasma and urine | AR, four genes at 22q11.1-q11.2 are involved | Amino acid analysis, direct measurement of glutathione, enzyme
assay | No specific treatment |
5-oxoprolinase deficiency | Not consistent | Gross urinary excretion of 5-oxoproline, no metabolic acidosis | AR, at least two genes code for two subunits | Urinary analysis of organic acids, enzyme assay | No specific treatment |