engleski

Whole blood S-adenosylhomoysteine - a reliable biomarker of S-adenosylhomocysteine hydrolase deficiency

S-adenosylhomocysteine hydrolase (AdoHcyase) deficiency is a recently reported inherited multisystemic disorder of sulfur amino acod metabolism with myopathy present at birth. The diagnosis of this disorder has so far been confirmed in five patients. Our experience with three patients indicated that early diagnosis and introduction of methionine restriction diet and supplementation with phosphatidylcholine and creatine may improve clinical outcome. Elevated plasma S-adenosylhomocysteine (AdoHcy) seems to be a reliable biomarker of the disease. Unfortunately, hypermethioninemia as a marker important also for neonatal screening, may be absent or nonsignificant. Unspecific laboratory changes include elevation of creatine kinase (up to 70x normal)and aminotransferases (up to 4x normal). In this study we checked if whole blood AdoHcy could be a useful biomarker of the disease. We measured AdoHcy and S-adenosylmethionine (AdoMet) concentration in perchloride acid-treated whole blood by HPLC with UV-detection (modification by Fux R. et al., 2005). In three patients in the period of normal diet, AdoHcy was 6.5 - 24-fold higher than the reference range, previously not reported in children (n=75). AdoMet/AdoHcy ratio was also significantly decreased, i.e. down to 18x normal. Therefore, AdoHcy and AdoMet/AdoHcy ratio in whole blood could be useful biomarkers for the diagnosis of AdoHcyase deficiency, particularly in laboratories without tandem mass spectrometry and sensitive HPLC detectors. This is additionally important since our past studies indicated that the disease might be largely underdiagnosed.

S-adenosylhomocysteine hydrolase deficiency; biomarker

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