The biochemical profile and dietary management in S-adenosylhomocysteine hydrolase deficiency

S-Adenosylhomocysteine (SAH) hydrolase deficiency is an autosomal recessive disorder in methionine metabolism caused by pathogenic variants in the gene AHCY. To date, only 15 patients with this disorder have been reported, including several patients treated with dietary management. In this study, we report a new case with SAH hydrolase deficiency and conduct a literature review with a focus on the biochemical profiles and the efficacy of dietary management. The biochemical markers associated with SAH hydrolase deficiency includes elevated levels of methionine, creatine kinase (CK), SAH, and S-Adenosylmethionine (SAM). However, half of the cases (6/12) had normal methionine levels at the initial evaluation. In contrary, SAM and SAH were markedly elevated in all reported patients at the initial evaluation (SAM: range 1.7× -53×, median 21.5×; SAH: range 4.9× −193.8×, median 98.1×). Nine patients were treated with methionine-restricted diet, which markedly reduced SAM and SAH in all patients but the levels did not normalize. CK and liver function did not show significant improvement with dietary treatment. The majority of patients (5/8) demonstrated clinical improvements with dietary management, such as increase in muscle strength; but all patients continued to experience developmental delay and two deaths were reported from cardiopulmonary arrest. This study suggests that methionine is not a reliable diagnostic biochemical marker for SAH hydrolase deficiency and SAM/SAH levels should be considered in the workup in neonates with unexplained hypotonia, liver dysfunction, or elevated CK. Dietary restriction of methionine demonstrates clinical benefits in some affected patients and should be trialed in patients with SAH hydrolase deficiency.