Respiratory chain complex III deficiency with pruritus: A novel vitamin responsive clinical feature☆,☆☆
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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Cited by (14)
Mitochondrial respiratory defect causes dysfunctional lactate turnover via AMP-activated protein kinase activation in human-induced pluripotent stem cell-derived hepatocytes
2015, Journal of Biological ChemistryCitation Excerpt :Taken together, it is likely that the lactic acidosis caused by mitochondrial dysfunction results not only from excessive lactate production in energy-consuming cell types but also from reduced capacity of lactate turnover by enhanced AMPK activity in hepatocytes. Although many drugs, including electron acceptors, antioxidants, and cofactors, such as coenzyme Q10, vitamins, succinate, carnitine, creatine monohydrate, and dichloroacetate, have been developed for the treatment of DMRC patients (48–57), any pharmacologic medication described to date is non-effective. To overcome this limitation for the recovery of mitochondrial respiration, genomic editing tools can be employed.
Therapeutic strategies for mitochondrial disorders
2015, Pediatric NeurologyCitation Excerpt :In a patient with global developmental delay, pruritus, elevated plasma bile acid levels, and liver cirrhosis, symptomatic and bioenergetic improvement was reported.56 Pruritus and elevated bile acid levels decreased on treatment with menadione and vitamin-C.56 Vitamin-K is a fat-soluble vitamin and acts as a cofactor of the γ-glutamyl carboxylase.
Quinone analogues regulate mitochondrial substrate competitive oxidation
2004, Biochemical and Biophysical Research CommunicationsMitochondrial DNA mutations and oxidative stress in mitochondrial diseases
2003, Advances in Clinical Chemistry
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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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