2-ketoglutarate dehydrogenase deficiency with intermittent 2-ketoglutaric aciduria.

2-ketoglutarate dehydrogenase (KGD) deficiency is a rare disorder of the tricarboxylic acid cycle. To date, 7 patients have been reported with clinical symptoms suggesting a neurodegenerative disease. We report a new patient in whom urinary excretion of 2-ketoglutaric acid (KGA) was intermittently found to be within normal ranges. At birth, the male patient suffered from mild perinatal asphyxia due to meconium aspiration. During the first months of life, he developed an opisthotonus, hyperexcitability and truncal hypertonia. At the present age of 14 months, these neurological symptoms became less 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 months of age (5-1700 mmol/mol creatinine, controls: < 340 mmol/mol creatinine). 2-KGA was not increased in plasma and CSF. Diagnosis was confirmed by measurement of decreased 2-KGD activity in cultured skin fibroblasts. This report demonstrates that the diagnosis of 2-KGD deficiency can easily be missed. In case of doubt, 2-KGD activity should be measured in fibroblasts. The clinical and long-term outcome of patients with 2-KGD deficiency is unknown. Further reports and long-term evaluation are required.