Coenzyme Q10 Deficiency, Primary, 6

A number sign (#) is used with this entry because of evidence that primary coenzyme Q10 deficiency-6 (COQ10D6) is caused by homozygous or compound heterozygous mutation in the COQ6 gene (614647) on chromosome 14q24.

For a general phenotypic description and a discussion of genetic heterogeneity of primary coenzyme Q10 deficiency, see COQ10D1 (607426).

Description

Primary coenzyme Q10 deficiency-6 is an autosomal recessive disorder characterized by onset in infancy of severe progressive nephrotic syndrome resulting in end-stage renal failure and sensorineural deafness. Renal biopsy usually shows focal segmental glomerulosclerosis (FSGS). Some patients may show a favorable response to oral coenzyme Q supplementation (summary by Heeringa et al., 2011).

For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278) and NPHS1 (256300).

Clinical Features

Heeringa et al. (2011) reported 11 children from 5 families with autosomal recessive coenzyme Q10 deficiency manifest as nephrotic syndrome. Nine of the 11 patients had sensorineural deafness. The patients presented with proteinuria at a median age of 1.2 years (range, 0.2-6.4 years) and progressed to end-stage renal failure at a median age of 1.7 years (range, 0.4-9.3 years). Five children died in early childhood (median age of 5.0 years). Renal biopsy showed focal segmental glomerulosclerosis in 7 patients and diffuse mesangial sclerosis (DMS) in 1. Other abnormalities included seizures in 1 patient, and white matter abnormalities, seizures, and multiorgan failure in another. Two other patients had ataxia and facial dysmorphism, respectively. Three patients showed variable, but favorable, response to oral coenzyme Q treatment.

Molecular Genetics

By positional cloning, Heeringa et al. (2011) identified homozygous or compound heterozygous pathogenic mutations in the COQ6 gene (614647.0001-614647.0004) in 11 children from 5 families with autosomal recessive coenzyme Q deficiency manifest as nephrotic syndrome. Subsequent analysis of the COQ6 gene in 530 families with nephrotic syndrome identified 2 heterozygous truncating mutations in 2 unrelated patients (614647.0005 and 614647.0006, respectively); a second pathogenic mutation was not found in these 2 patients.