Respiratory chain complex III deficiency with pruritus: A novel vitamin responsive clinical feature,☆☆

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Abstract

We report a child with an isolated complex III respiratory chain deficiency and global developmental delay who had severe pruritus with elevated plasma bile acid levels. A liver biopsy showed micronodular cirrhosis, and enzymologic evaluation demonstrated an isolated complex III deficiency in both liver and muscle. His pruritus improved and serum bile acid levels decreased after treatment with menadione and vitamin C. (J Pediatr 1999;134:352-4)

Section snippets

CASE REPORT

The proband is the third child born to first cousin Lebanese parents. The pregnancy was complicated by intrauterine growth retardation. He was delivered by emergency cesarean section at 36 weeks, weighing 1995 g (<3rd percentile), length 40 cm (<3rd percentile), and head circumference 31 cm (10th percentile). He had failure to thrive and at 4 months was noted to have developmental delay, hepatomegaly (palpable 2 to 3 cm below the costal margin), poor muscle bulk, marked hypotonia, and weakness

RESULTS

Routine light microscopy and immunohistochemistry of the muscle were normal. The liver biopsy showed micronodular cirrhosis with no evidence of active inflammation, cholestasis, steatosis, or storage. Electron microscopy of muscle and liver showed mild mitochondrial pleomorphism with increased matrix density, no inclusions, and normal peroxisomes.

Respiratory chain enzymes in skeletal muscle had residual activities of ~130% for complexes I, II, and IV but only 35% for complex III (all expressed

DISCUSSION

This case highlights the complexities in the diagnosis of defects of the mitochondrial respiratory chain and brings to attention a previously unreported problem of disproportionate elevation of plasma bile acid levels in the absence of jaundice or liver failure.

The diagnosis of an autosomal recessive mitochondrial disorder is suggested by the parent’s consanguinity, our patient’s profound developmental delay, growth failure, liver disease, mild and inconsistent lactic acidemia, pleomorphic

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Reprint requests: John Christodoulou, Western Sydney Genetics Program, Royal Alexandra Hospital for Children, Hawkesbury Rd, Westmead 2145, NSW Australia.

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