COQ7 ‐Related Neuropathy: Two New Cases and Review of the Literature

BACKGROUND AND AIMS: Biallelic variants in COQ7 have been associated with inherited neuropathy. COQ7 encodes a mitochondrial protein directly involved in coenzyme Q10 (CoQ10) biosynthesis. METHODS: Two unreported and unrelated cases of COQ7-related neuropathy are presented, along with a review of all previously published cases to highlight the key clinical features. The frequency of COQ7 variants was assessed in our cohort of distal hereditary motor neuropathy (dHMN) patients with upper motor neuron (UMN) signs. RESULTS: The two patients were compound heterozygous for the COQ7 variants c.197T>A, p.(Ile66Asn) and c.478del, p.(Asp160Thrfs*11); the latter has not been reported. Symptoms began in childhood, and both were diagnosed with dHMN based on distal motor weakness predominantly affecting the lower limbs and a pure motor length-dependent axonal neuropathy on electrodiagnostic study. They had pes cavus and brisk reflexes. In the 28 patients identified in the literature, including the two reported herein, the median age at symptom onset was 10 years (IQR 5-11). The predominant neuropathy subtype was dHMN (89%). Foot deformities were observed in 19/23 patients (83%). Signs of UMN involvement were present in 20/27 patients (74%). In fibroblasts, CoQ10 levels were low, and 6-demethoxy-CoQ10 (DMQ10) levels were elevated in all tested patients (8/8, 100%). No other case was identified in 71 patients with dHMN and UMN signs. INTERPRETATION: COQ7-related neuropathy is rare but should be considered in young patients presenting with distal hereditary motor neuropathy, especially when UMN signs are present. Elevated DMQ10 levels and low CoQ10 levels in fibroblasts represent valuable diagnostic biomarkers.