engleski

S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency: myopathy seems to be congenital

AdoHcy hydrolase deficiency is a recently reported inherited disease caused by disorder in methionine metabolism. Here, we report the second case (the brother of the previously reported boy) and a third confirmed case. The affected brother of the index patient is now age 20 months. He was born at term, with normal Apgar score. Since birth he was hypotonic with diminished spontaneous activity. Contact was sluggish. Tendon reflexes could not be elicited. Some of the primitive reflexes were weak or absent. Creatine kinase has always been high, from more than 10, 000 in the first weeks to about 1000-2000 U/L in follow-up period. At 3 months, 11 days, brain MR showed mildly delayed myelination and significantly enlarged subarachnoid spaces in frontal and temporoparietal regions. Highest plasma methionine was around the normal upper limit. Plasma S-adenosylmethionine (AdoMet) was 2.5-17 x normal and AdoHcy 7-15 x normal. In contrast to his brother, his serum albumin has been normal and clotting parameters either normal or only slightly and transiently abnormal. As in his brother, AdoHcy hydrolase activity in RBCs was low and the same two exon 4 point mutations were present. Low methionine diet, phosphatidylcholine and creatine supplementation were started at age 102-107 days. Better contact, activity, and muscle strength occurred gradually. Brain MR, repeated at age of 10 and half months, showed significant improvement with almost normal myelination. The third patient, very recently confirmed, is a mildly mentally retarded adult monitored since infancy because of myopathy and isolated hypermethioninemia. In plasma, AdoMet was 19-21 x normal and AdoHcy 19-28 x normal. RBC AdoHcy hydrolase activity was 20-30 % of the mean normal value. His gene encoding AdoHcy hydrolase had two mutations: Y143C (present in the sibling brothers) and a novel mutation, A89V.

AdoHcy hydrolase; methionine; myopathy

Journal of Inherited Metabolic Disease 28 (2005) S1 (76-76) ; ISSN 0141-8955