S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man

Abstract

This paper reports the third proven human case of deficient S-adenosylhomocysteine (AdoHcy) hydrolase activity. The patient is similar to the only two previously reported cases with this disorder in having severe myopathy, developmental delay, elevated serum creatine kinase (CK) concentrations, and hypermethioninaemia. Although he has been followed from infancy, the basic enzyme deficiency was established only at age 26 years. The diagnosis was based on markedly elevated plasma concentrations of both AdoHcy and S-adenosylmethionine, some 20% of the mean control activity of AdoHcy hydrolase activity in haemolysates of his red-blood cells, and two missense mutations in his gene encoding AdoHcy hydrolase. He had low values of erythrocyte phosphatidylcholine and plasma free choline and marginally elevated excretion of guanidinoacetate, suggesting that the elevated AdoHcy may have been inhibiting methylation of phosphatidylethanolamine and guanidinoacetate. His leukocyte DNA was globally more methylated than the DNA's of his parents or the mean extent of methylation measured in age-matched control subjects.

Fig. 1

Electron photomicrograph of liver at age 14 months showing a giant misshapen mitochondrion with paracrystalline inclusions

Fig. 2

Gomori trichrome staining of cross-section of quadriceps muscle at age 14 months. Note the normal appearance of most of the cells. A, deeply staining cells, most of which are larger than normal; B, two partially degenerated myocytes; C, a degenerated myocyte infiltrated with macrophages

Fig. 3

Electron photomicrograph of quadriceps muscle at age 14 months showing one normal myocyte (D), and one necrotic one (E)