Dihydrolipoamide dehydrogenase deficiency: a still overlooked cause of recurrent acute liver failure and Reye-like syndrome.

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.

[Therapeutic effect of hepatoprotectors in experimental Reye syndrome]. / [Gepatoprotektory okazyvaiut lechebnoe deistvie pri éksperimental'nom sindrome Reie]

Maxar and legalon--hepatoprotectors containing polyphenols--exhibit a therapeutic effect with respect to the experimental Reye's syndrome induced in rats by intraperitoneal injections of 4-pentenoic acid. Maxar restores the activity of enzymes of the hepatic origin, normalizes the content of bilirubin, glucose, phenols, and malonic aldehyde in the blood serum, stimulates the production of ketone bodies and ammonia detoxication, and improves the histologic structures of liver and cortex. Legalon also decreases the structural-metabolic disorders accompanying the Reye's syndrome, but to as lower ewxtent.

Reye syndrome: results of intensive supportive care.

Thirty-six patients with Reye syndrome were admitted to St. Louis Children's Hospital during a ten-year period from January, 1966, through June, 1975; ten patients (28%) died. Seven (64%) of the ten deaths occurred in the 11 patients admitted between 1966 and 1971, whereas only three (12%) of 25 patients died thereafter. We attribute this reduction in case fatality rate to early diagnosis, recognition of milder cases, and intensive medical support including continuous intravenous infusion of hypertonic glucose, intermittent infusion of hypertonic mannitol, and early elective endotracheal intubation. Analyses of metabolic, hormonal, and blood gas data obtained serially during the acute illness in 16 of these patients provide a basis for a discussion of the pathophysiology of this disorder.