engleski

The fourth S-adenosylhomocysteine hydrolase deficient patient : Further evidence of congenital miopathy

S-Adenosylhomocysteine (AdoHcy) hydrolase (AdoHcyase) deficiency is a recently reported inherited disorder of sulfur AdoHcyase deficiency in a human. This patient, now at age 7 months, is the youngest brother of two previously reported AdoHcyase-deficient Croatian boys. Prenatal diagnosis was declined. He was born at term with Apgar score 8/9. Since birth he exhibited clear signs of myopathy: shallow breathing, floppiness and generalized muscle weakness with diminished spontaneous activity. Tendon reflexes could not be elicited. Primitive reflexes were weak or absent. Head control was poor. Contact was sluggish. At age 15 days brain MR showed delayed myelination. Creatine kinase (CK) was markedly elevated to 70x normal at age 16 days. Alanine (ALT) and aspartate (AST) aminotransferases were elevated to 4x normal. Plasma methionine was normal. At age 3 days whole blood S-adenosylmethionine (AdoMet) and AdoHcy were 1.8- and 6.5-fold above their reference ranges. Sequencing of the exon 4 of the AdoHcyase gene revealed the same two mutations present in both older brothers: a maternally derived mutation that introduces a premature stop codon at amino acid 112, and a paternally derived mutation that replaces a tyrosine 143 by a cysteine. Low methionine diet and oral phosphatidylcholine supplementation were started at age 18 days. Oral creatine was added 1 month later. He gradually gained strength, became more alert with better contact and spontaneous activity. In contrast to his brothers, at least presently, his muscle tone is more hypertonic than hypotonic. In the follow-up period CK remained elevated up to 9x normal. AST became normal, but ALT remained elevated up to 2x normal. AdoMet was normal and AdoHcy dropped markedly to 1.5-fold above its reference range. This case provides further evidence that AdoHcyase deficiency is a congenital multisystemic disorder, with myopathy present at birth. Pathogenesis is still unclear, but considering the critical role of methylation in various cellular processes, we assume that elevation of AdoHcy, a potent inhibitor of transmethylation reactions, plays a significant part in causing clinical abnormalities. This disease might serve as a model for the study of the variety of conditions in which total homocysteine is abnormally elevated. Under such circumstances, the ready reversibility of the AdoHcyase reaction leads necessarily to secondary elevations of AdoHcy.

congenital miopathy; S-adenosylhomocysteine hydrolase deficiency

nije evidentirano