Clinical Presentations of Coenzyme Q10 Deficiency Syndrome

Abstract

Coenzyme Q₁₀ (CoQ₁₀) deficiency is a clinically and genetically heterogeneous syndrome which has been associated with 5 major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia, and (5) isolated myopathy. Of these phenotypes, cerebellar ataxia and syndromic or isolated nephrotic syndrome are the most common. CoQ₁₀ deficiency predominantly presents in childhood. To date, causative mutations have been identified in a small proportion of patients, making it difficult to identify a phenotype-genotype correlation. Identification of CoQ₁₀ deficiency is important because the disease, in particular muscle symptoms and nephropathy, frequently responds to CoQ₁₀ supplementation.

Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9

“…To date, defects in eight of these genes were identified as a cause of primary CoQ 10 deficiency disorders (PDSS1, PDSS2, COQ2, COQ4, COQ6, ADCK3, ADCK4 and COQ9), a clinically heterogeneous group of diseases, which frequently manifests in childhood. 3,4 According to Quinzii et al, 5 five major clinical phenotypes can be distinguished: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) nephropathy, (4) cerebellar ataxia and (5) isolated myopathy. Identification of CoQ 10 deficiency is important because CoQ 10 supplementation can be beneficial in certain conditions.…”

A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C‐methyltransferase deficiency

“…Diseases of CoQ 10 deficiency have been reported in over 100 individuals worldwide. Their heterogeneous clinical features are consistent with one of five major phenotypes (Quinzii, Emmanuele, & Hirano, ): (1) Encephalopathy, associated with mitochondrial myopathy and myoglobinuria (Boitier et al., ; Ogasahara, Engel, Frens, & Mack, ; Salviati et al., ; Sobreira et al., ); (2) severe infantile disease with multi‐systemic involvement (Desbats et al., ; Dinwiddie et al., ; Quinzii et al., ; Rotig et al., ); (3) ataxia with cerebellar atrophy, the most common form, variably associated with seizures, cognitive impairment, muscle weakness, neuropathy, and hypogonadism (Gironi et al., ; Lagier‐Tourenne et al., ; Musumeci et al., ); (4) nephropathy, with or without sensory hearing loss (Ashraf et al., ; Diomedi‐Camassei et al., ; Heeringa et al., ; McCarthy et al., ); and (5) isolated myopathy (Gempel et al., ; Horvath et al., ; Lalani et al., ). In the past decade, next‐generation sequencing techniques have facilitated molecular diagnosis of these patients, enabling further elucidation of genotype–phenotype correlations (Yubero et al., ).…”

Biochemical Assessment of Coenzyme Q10 Deficiency

“…CoQ 10 deficiency impairs oxidative phosphorylation and causes clinically heterogeneous mitochondrial diseases [21,22]. When the decrease in CoQ 10 content is due to mutations in genes encoding proteins of the CoQ biosynthesis pathway or its regulation (COQ genes), it causes primary CoQ 10 deficiency [23,24].…”