Dihydrolipoamide dehydrogenase deficiency: A still overlooked cause of recurrent acute liver failure and Reye-like syndrome
| Autor: | J.-P. Cervoni, Laurence Hubert, Daniel Rabier, Audrey Boutron, Florence Lacaille, Séverine Valmary-Degano, Pascale de Lonlay, Chris Ottolenghi, Vincent Di Martino, Jean-Baptiste Arnoux, Anaïs Brassier, Yves de Keyzer, Dominique Chretien, Anne-Marie Bertrand |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Urinary system Disease Biology Fatty acid beta-oxidation Biochemistry Gastroenterology Endocrinology Maple Syrup Urine Disease Internal medicine Genetics medicine Humans Reye's syndrome Child Molecular Biology Dihydrolipoamide Dehydrogenase Acidosis Dihydrolipoamide dehydrogenase Muscles Reye Syndrome Metabolic disorder Infant Liver Failure Acute medicine.disease Pyruvate dehydrogenase complex Liver Algeria Mutation Acidosis Lactic Female medicine.symptom |
| Zdroj: | Molecular Genetics and Metabolism. 109:28-32 |
| ISSN: | 1096-7192 |
| Popis: | The causes of Reye-like syndrome are not completely understood. Dihydrolipoamide dehydrogenase (DLD or E3) deficiency is a rare metabolic disorder causing neurological or liver impairment. Specific changes in the levels of urinary and plasma metabolites are the hallmark of the classical form of the disease. Here, we report a consanguineous family of Algerian origin with DLD deficiency presenting without suggestive clinical laboratory and anatomopathological findings. Two children died at birth from hepatic failure and three currently adult siblings had recurrent episodes of hepatic cytolysis associated with liver failure or Reye-like syndrome from infancy. Biochemical investigation (lactate, pyruvate, aminoacids in plasma, organic acids in urine) was normal. Histologic examination of liver and muscle showed mild lipid inclusions that were only visible by electron microscopy. The diagnosis of DLD deficiency was possible only after genome-wide linkage analysis, confirmed by a homozygous mutation (p.G229C) in the DLD gene, previously reported in patients with the same geographic origin. DLD and pyruvate dehydrogenase activities were respectively reduced to 25% and 70% in skin fibroblasts of patients and were unresponsive to riboflavin supplementation. In conclusion, this observation clearly supports the view that DLD deficiency should be considered in patients with Reye-like syndrome or liver failure even in the absence of suggestive biochemical findings, with the p.G229C mutation screening as a valuable test in the Arab patients because of its high frequency. It also highlights the usefulness of genome-wide linkage analysis for decisive diagnosis advance in inherited metabolic disorders. |
| Databáze: | OpenAIRE |
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