ADCK3‐related Coenzyme Q10 Deficiency: A Potentially Treatable Genetic Disease

Abstract

Background Disorders related to dysfunction of coenzyme (CoQ10) metabolism, including AarF domain containing kinase 3 gene (ADCK3) mutations, have received attention due to the potential for response to CoQ10 supplementation. Methods We describe two new cases of neurological syndromes due to ADCK3 mutations that obtained striking benefit from CoQ10, and a third who did not. We also review 20 cases from the literature in which responses to CoQ10 were documented out of all 38 previously reported cases. Results Despite the remarkable responses in some cases with ataxia and movement disorders (myoclonus, dystonia, tremor), overall, we were not able to identify variables that predicted response to CoQ10 supplementation. Conclusions Based on our experience and data from the literature, we recommend a minimum of 10 mg/kg/day of ubiquinone with titration up to 15 mg/kg/day, maintained at least for 6 months in order to obtain or exclude potential benefit from therapy.

One-year outcome of coenzyme Q10 supplementation in ADCK3 ataxia (ARCA2)

“…CoQ10 (Ubidecarenone) oral capsule was prescribed, titrated up to 15 mg/kg/die, distributed in three daily administrations at meal time [1] (all patients assumed the same product and continued other medications and physical therapy).…”

“…Autosomal Recessive Cerebellar Ataxia 2 (ARCA2) is a rare and heterogeneous condition, including cerebellar ataxia, exercise intolerance, epilepsy, dystonia, and mild intellectual disability. Age of onset ranges from typical early childhood to adulthood, while the clinical course is mild or moderate [1, 2]. ARCA2 is due to biallelic mutations of ADCK3 gene, which encodes for a UbiB family kinase, involved in biosynthesis of Coenzyme Q10 (CoQ10), an electron carrier and endogenous antioxidant.…”

“…The identification of the pathophysiological background prompted several attempts to treat ARCA2 with CoQ10 oral supplementation. The clinical response has been described as inconstant, unpredictable and variable among patients [1, 4], although the genetic background may have a role [3]. Actually, the literature is scarce or anecdotal, and mainly results from retrospective analysis.…”

COQ2 mutation associated isolated nephropathy in two siblings from a Chinese pedigree

“…Central nervous system (CNS) involvement is essential. Extra-CNS impairment has not been observed [5].…”

Disorders of Human Coenzyme Q10 Metabolism: An Overview

“…In humans, mutations in 10 of these genes have been identified to date: the corresponding gene products respectively are PDSS1 (phenyl diphosdphate synthase subunit 1; [ 27 ]), PDSS2 (decaprenyl diphosphate synthase subunit 2; [ 28 ]) COQ4 (multienzyme complex organisation enzyme; [ 29 ]), COQ5 (methyltransferase; [ 30 ]), COQ6 (monooxygenase; [ 31 ]), COQ7 (DMG hydroxylase; [ 32 ], ADCK3 (renamed COQ8A, protein kinase; [ 33 ]), ADCK4 (renamed COQ8B, protein kinase; [ 34 ]) and COQ9 (lipid-binding protein; [ 35 ]).…”