[MIM 613 752]

A few cases described. Autosomal recessive transmission or de novo mutation of the AHCY gene (20q11.22) coding for the S-adenosylhomocysteine hydrolase, an enzyme involved in methionine metabolism. Excess S-adenosylhomocysteine inhibits numerous methyltransferases, thus modifying DNA methylation and the expression of other genes during embryogenesis and after birth.

This is one of the causes of hypermethioninemia: the others are tyrosinemia [MIM 276,700], cystathionine beta-synthase deficiency [MIM 236,200] and methionine adenosyltransferase deficiency [MIM 250,850].

The disease is generally severe with a poor prognosis in terms of development, but the phenotype can vary with mild or asymptomatic forms (one case).

The following may be observed

-        death in utero: hydrops

-        developmental delay and hypotonia due to a destructive myopathy associated with markedly elevated creatine kinase (CK) levels and sometimes cerebral hypomyelination, coagulation disorders and hepatopathy. Microcephaly, strabismus and behavioural disorders are common.

-        severe cases: congenital cerebral anomalies (hypoplasia of the pons and cerebellum, hypoplasia of the corpus callosum), liver failure, respiratory insufficiency due to severe muscle weakness, and death in early childhood.

-        mild phenotype: later onset with muscle weakness and developmental delay. Risk of hepatocellular carcinoma.

Diagnosis: markedly elevated plasma levels of S-adenosylhomocysteine and S-adenosylmethionine in association with normal or near-normal levels of homocysteine; hypermethioninemia is not always observed, particularly in early childhood.

Treatment: low-methionine diet with supplementation with a mixture of non-methionine amino acids. Supplementation with phosphatidylcholine, creatine and cysteine may be beneficial. Liver transplantation was associated with an improvement in clinical and biochemical parameters in one patient.

Anesthetic implications: 

check liver function and hemostasis; echocardiography; hypotonia, mental retardation; given the destructive myopathy (images similar to biopsies of Duchenne and Becker myopathies), it may be prudent to avoid succinylcholine and halogenated agents; risk of rhabdomyolysis: check hydration, positioning, avoid use of tourniquets.

References : 

-        Van Gorkom CR, Black ED, Karlik JB.
Anesthetic management of a patient with S-adenosylhomocysteine hydrolase deficiency: a case report.
A&A Practice 2022;16:e01578

Updated: June 2023