Dihydrolipolipoamide dehydrogenase deficiency in Southern israel: a rare disease with a change of natural history

Orna Staretz Chacham Eyal Kristal Eli Hershkovitz
Pediatrics, Soroka Medical Center, Ben- Gurion University

Pyruvate dehydrogenase complex (PDHC) is composed of 3 components: E1 which is the rate limiting enzyme, E2 and E3. E3 is a flavoprotein - Dihydrolipoamide Dehydrogenase (DLD- E3; MIM * 238331; EC 1.8.1.4) is common to all 2-ketoacid dehydrogenases. Defects in the PDHC leads to abnormal conversion of pyruvate into lactate instead of acetyl –CoA through the TCA cycle. Deficiency of PDHC interferes with energy production from glycolysis. Therefore PDHC deficiency, and DLD- E3 deficiency as part of it, aggravates lactic acidosis by carbohydrates consumption. DLD- E3 is a rare autosomal recessive inherited disorder. Approximately 28 cases have been reported worldwide. The gene for DLD- E3 is located on 7q31-q32. At least 17 mutations in the DLD gene have been found to cause dihydrolipoamide dehydrogenase deficiency. The clinical spectrum of DLD-E3 deficiency is known to be very wide regarding age of presentation, type of manifestation and severity of the disease. Consanguinity increases the frequency. Over the last 20 years more than 10 cases have been reported in Southern Israel. All of our patients were homozygous to the same mutation and presentation were similar, however, disease progression and survival have been highly different with a changing pattern over the years as will be presented and discussed.




Powered by Eventact EMS