Abstract
Disorders of sulfur amino acid metabolism can affect methionine demethylation, homocysteine (Hcy) remethylation, Hcy transsulfuration (including classical homocystinuria), glutathione synthesis or cysteine/hydrogen sulfide oxidation. There may be altered blood or urinary concentrations of methionine, AdoMet, sarcosine, AdoHcy, total Hcy and cysteine, cystathionine, hydrogen sulfide, sulfite, thiosulfate or adenosine.
The commonest methionine demethylation disorder is MAT I/III deficiency: this is often benign but can cause neurodevelopmental problems. Other features of demethylation disorders include liver disease (GNMT deficiency), myopathy (SAHH and ADK deficiencies), facial dysmorphism (ADK deficiency) or halitosis (MTO and MAT I/III deficiency).
Methionine restriction may be beneficial in some patients with MAT I/III or ADK deficiency, CBS deficiency (classical homocystinuria) is the commonest disease in this group. Its severity ranges from a multisystemic childhood condition (with lens dislocation, osteoporosis, marfanoid features, central nervous system and vascular complications) to an isolated thromboembolic disease in adults.
Treatment is primarily with pyridoxine in pyridoxine-responsive patients and a low-methionine diet +- betaine in non-responders. Treatment can prevent most complications even in pyridoxine non-responsive patients if they are diagnosed by neonatal screening.
The other transsulfuration disorder, CTH deficiency, appears to be benign. Disorders of cysteine and hydrogen sulfide oxidation include SQOR deficiency, ethylmalonic encephalopathy, isolated SUOX deficiency and combined SUOX/xanthine oxidase deficiency due to impaired molybdenum cofactor (MoCo) synthesis.
These are severe disorders with early-onset seizures or neurological complications; other problems may include diarrhoea, petechiae, acrocyanosis, lens dislocation or urolithiasis. MoCo deficiency type A can be treated with a synthetic precursor of the cofactor and ethylmalonic encephalopathy may profit from liver transplantation.