2-ketoglutarate dehydrogenase deficiency with intermittent 2-ketoglutaric aciduria

2-ketoglutarate dehydrogenase (KGD) deficiency is a rare disorder of the tr icarboxylic acid cycle. To date, 7 patients have been reported with clinica l symptoms suggesting a neurodegenerative disease. We report a new patient in whom urinary excretion of 2-ketoglutaric acid (KGA) was intermittently f ound to be within normal ranges. At birth, the male patient suffered from m ild perinatal asphyxia due to meconium aspiration. During the first months of life, he developed an opisthotonus, hyperexcitability and truncal hypert onia. At the present age of 14 months, these neurological symptoms became l ess pronounced. A cranial MRI was normal. Urinary 2-KGA excretion was found to be intermittently increased in 3 of 6 analyses between 2 weeks and 14 m onths of age (5-1700 mmol/mol creatinine, controls: <340 mmol/mol creatinin e). 2-KGA was not increased in plasma and CSF. Diagnosis was confirmed by m easurement of decreased 2-KGD activity in cultured skin fibroblasts. This r eport demonstrates that the diagnosis of 2-KGD deficiency can easily be mis sed. In case of doubt, 2-KGD activity should be measured in fibroblasts. Th e clinical and long-term outcome of patients with 2-KGD deficiency is unkno wn. Further reports and long-term evaluation are required.