NOVEL MUTATION OF THE ELECTRON TRANSFERRING FLAVOPROTEIN DEHYDROGENASE (ETFDH) GENE IN THE ISOLATED MYOPATHIC FORM OF COENZYME q10 DEFICIENCY.

LETTER TO THE EDITORCoenzyme Q10 (CoQ 10 or ubiquinone) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions (8). CoQ 10 deficiency is thought to be an autosomal recessive condition. CoQ 10 deficiency is a heterogeneous clinical and genetic disease group and five different phenotypes have been described to date (7): an encephalomyopathic phenotype with mitochondrial myopathy, recurrent myoglobinuria and encephalopathy (5,9), a multisystem infantile phenotype with encephalomyopathy and renal failure (1), Leigh syndrome which is characterized with encephalopathy, growth retardation, ataxia, and deafness (10), a cerebellar phenotype with cerebellar atrophy and ataxia (4), and an isolated myopathic phenotype (3).Blocks in different levels of complex biosynthetic way of CoQ 10 lead to clinical heterogeneity and it is supported by increased numbers of defined molecular defects in different clinical variants (2). Herein we report a patient with isolated myopathy and CoQ 10 deficiency.A 20 year-old boy with neuromuscular disease who presented to our unit had proximal muscle weakness, fatigue, and exercise intolerance. His parents were non-consanguineous and there was no family history of similar disorders. On neurological examination, there was shamble, moderate weakness of proximal muscles of the extremities and decreased deep tendon reflexes. Gower's sign was negative and sensation was normal. The rest of general physical examination revealed no abnormal findings.Serum creatine kinase (CK) was elevated at 890 to 2628 U/l (normal Late-onset multiple acyl-CoA dehydrogenase deficiency was suspected and high doses of oral carnitine treatment was initiated. After 1 month of oral carnitine supplementation, CK levels returned to normal and his subjective complaints were completely resolved. However, six months later, his symptoms reappeared and serum CK levels (2628 U/l), liver enzymes (GOT 327 U/l, normal To confirm the diagnosis, mutational analysis for the ETFDH gene was performed by direct DNA sequencing. We identified two novel heterozygous mutations in the patient. The first one was c.1384C>G, located at the exon 11, changed leucine to valine at amino acid position 462 (p.L462V) (Fig. 1), and the second one was c. 1468+ldelG in intron 11 (Fig-2).In the family, the healthy mother, brother and grandfather were heterozygous mutation carriers for c.l468+ldelG and the healthy father was heterozygous mutation carrier for c.1384C>G (Fig. 3). These mutations p.(Leu462Val)/c.l384C>G and c. 1468+ldelG have never been reported in the literature or in the Human Gene Mutation Database (HGMD) (http://www.hgmd.cf.ac.uk/ac/index.php). In sequencing analysis of exon 11 and intron 11 of ETFDH gene on 100 healthy individuals, we did not detect these changes.In 2005 Lalani et al. described a case of isolated myopathic form of CoQ 10 deficiency in an 11.5 year old girl for the first time and Gempel et al. defined its correlation with ETFDH gene in 2007 (2,3).Gempel et al. (2) asserted that late onset GAII and isolated myopathic form of CoQ 10 deficiency may be allelic diseases on detecting homozygous or compound heterozygous ETFDH mutations in seven patients from five different families who fulfilled the clinical, histological and biochemical criteria of isolated myopathic form of CoQ 10 deficiency. …