Homocystein as an important diagnostic marker of remethylation defects – A case report

Introduction: In the diagnostic work-up of unclear neurologic diseases many biochemical tests are routinely performed in the metabolic screening. Among these homocysteine is less well established and hyperhomocysteinemia is not detected by newborn screening programs. Nevertheless hyperhomocysteinemia serves as a reliable diagnostic marker for a variety of treatable enzyme defects in folate- cobalamin- and methionine metabolism, which may present with a broad spectrum of neurologic and haematologic symptoms. We report on a patient with a rare remethylation defect.

Case history: 2nd child of a healthy, consanguineous couple from Austria. Pregnancy and delivery were uneventful. By the end of the 1st year ataxic gait was evident. A cranial MRI was normal. In the 3rd year of life the child exhibited acute neurologic deterioration in the course of pneumonia, leading to respiratory failure and mechanical ventilation. Cranial MRI showed global brain atrophy and a non-recent thrombosis of the saggital sinus, while the myelon was normal. Due to pancytopenia and macrocytic anemia plasma folic acid and cobalamin were measured but gave normal results, methylmalonic acid in urine was normal. Plasma homocysteine in serum was markedly elevated to 188µmol/l. Plasma methionine was as low as 3µmol/l, pointing towards a remethylation defect. Treatment with daily injections of hydroxycobalamin, 1mg and oral supplementation of folate, 10mg and betaine, 200mg/kg/day lead to rapid normalisation of blood count, plasma homocysteine and plasma aminoacids. Also from the neurologic point of view the child showed continuous improvement but 6 weeks after initiation of specific treatment, is still not able to walk independently.

Conclusions: In view of the clinical and biochemical findings our patient suffers from a remethylation defect (most likely cobalamine E/G deficiency); biochemical and complementation studies are pending. Despite treatment options with cofactor- and betaine supplementation diagnostic delay bears the risk of irreversible brain damage and spinal cord d egeneration.