The myopathic form of coenzyme Q10 deficiency is caused by mutations in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene

Abstract

Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families with an isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological and biochemical presentation of our patients was very homogenous. All patients presented with exercise intolerance, fatigue, proximal myopathy and high serum CK. Muscle histology showed lipid accumulation and subtle signs of mitochondrial myopathy. Biochemical measurement of muscle homogenates showed severely decreased activities of respiratory chain complexes I and II + III, while complex IV (COX) was moderately decreased. CoQ10 was significantly decreased in the skeletal muscle of all patients. Tandem mass spectrometry detected multiple acyl-CoA deficiency, leading to the analysis of the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, previously shown to result in another metabolic disorder, glutaric aciduria type II (GAII). All of our patients carried autosomal recessive mutations in ETFDH, suggesting that ETFDH deficiency leads to a secondary CoQ10 deficiency. Our results indicate that the late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases. Since this condition is treatable, correct diagnosis is of the utmost importance and should be considered both in children and in adults. We suggest to give patients both CoQ10 and riboflavin supplementation, especially for long-term treatment.

The in-depth evaluation of suspected mitochondrial disease

“…Complex I structural subunits [151], B17.2L & NDUFAF1 [151], SDHA [152], SDHC [153], SDHD [153], BCS1L [154,155], SURF1 [156], SCO1 [157], SCO2 [158], COX10 [159], COX15 [160,161], ETHE1 [162], LRPPRC (LSFC) [138], ATP12 [163], PDSS1 [164], PDSS2 [165], COQ2 [164], APTX [166], ADCK3 [167], ETFDH [168], TSFM [169], TUFM [170], EGF1 [170], MRPS16 [171], PUS1 [172], DARS2 [173], PDHA1 [14], POLG1 [107], TK2 [174,175], DGUOK [176], MPV17 [137], SUCLA2 [177],SUCLG1 [177],RRM2B [178], TWINKLE [179], ANT1 [180], ABC7 [181], FXN [182], OPA1 [183], DDP1 [184], SPG7 [185,186], TAZ [187] …”

Perrault Sendromunun genetik patogenezi

“…For example; Alstrom syndrome has begun to be classsified as a ciliopathy (10). The late-onset form of GAII and the myopathic form of CoQ10 deficiency are allelic diseases and chylomicron retention disease and Marinesco-Sjogren syndrome are related (11,12). We suggest that, before proceeding with further laboratory investigations, clinical and neurological examinations must be fully performed and a correct diagnosis of the cases made as there are many syndromes sharing several findings.…”

Mitochondrial Disorders Therapy: The Utility of Melatonin~!2009-11-18~!2010-01-21~!2010-06-23~!

“…Other syndromes have also been associated with a secondary CoQ 10 deficiency. These include autosomal recessive cerebellar ataxia of unknown etiology in children and is caused by mutations in ADCK3 in adults [31,38], the syndrome of ataxia and oculomotor apraxia (AOA1) caused by mutations in the aprataxin gene (APTX) [39], and a predominantly myopathic form of glutaric aciduria type II (GAII) caused by mutations in the electron transfer flavo-protein dehydrogenase gene (ETFDH) [40]. The usual treatment of CoQ 10 deficient patients is the oral supplemen-tation with CoQ 10 .…”