Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10 deficiency

Abstract

Coenzyme Q(10) (CoQ) deficiency is an autosomal recessive disorder presenting five phenotypes: a myopathic form, a severe infantile neurological syndrome associated with nephritic syndrome, an ataxic variant, Leigh syndrome and a pure myopathic form. The third is the most common phenotype related with CoQ deficiency and it will be the focus of this review. This new syndrome presents muscle CoQ deficiency associated with cerebellar ataxia and cerebellar atrophy as the main neurological signs. Biochemically, the hallmark of CoQ deficiency syndrome is a decreased CoQ concentration in muscle and/or fibroblasts. There is no molecular evidence of the enzyme or gene involved in primary CoQ deficiencies associated with cerebellar ataxia, although recently a family has been reported with mutations at COQ2 gene who present a distinct phenotype. Patients with primary CoQ deficiency may benefit from CoQ supplementation, although the clinical response to this therapy varies even among patients with similar phenotypes. Some present an excellent response to CoQ while others show only a partial improvement of some symptoms and signs. CoQ deficiency is the mitochondrial encephalomyopathy with the best clinical response to CoQ supplementation, highlighting the importance of an early identification of this disorder.

Hereditary ataxias: overview

“…47 Coenzyme Q10 (CoQ10) deficiency is often associated with seizures, cognitive decline, pyramidal track signs, and myopathy but may also include prominent cerebellar ataxia. 48,49 The symptoms may respond to CoQ10 treatment.…”

Autosomal recessive ataxias: 20 types, and counting

“…The ataxic subtype is the most common presentation of CoQ10 deficiency 14,15 . It is characterized by progressive ataxia, cerebellar atrophy and reduced muscle CoQ10 14,15 .…”

“…It is characterized by progressive ataxia, cerebellar atrophy and reduced muscle CoQ10 14,15 . Early symptoms might include developmental delay, hypotonia and frequent falls.…”

“…Five clinical subtypes have been recognized: (1) Encephalomyophatic, with mitochondrial myopathy, recurrent myoglobinuria and CNS symptoms and signs; (2) Early infantile multisystemic, with severe visceral and brain manifestations; (3) Leigh syndrome; (4) Pure myopathic; (5) Ataxic 14,15,17 .…”

“…Primary deficiency of coenzyme Q10 (CoQ10) is a genetically heterogeneous disorder, with a highly variable clinical spectrum, which includes multi-systemic manifestations as well as CNS compromise [14][15][16] . Five clinical subtypes have been recognized: (1) Encephalomyophatic, with mitochondrial myopathy, recurrent myoglobinuria and CNS symptoms and signs; (2) Early infantile multisystemic, with severe visceral and brain manifestations; (3) Leigh syndrome; (4) Pure myopathic; (5) Ataxic 14,15,17 .…”