A case report of two novel mutations suggestive of combined deficiency of oxidative phosphorylation-39 (COXPD-39) in a patient with global development delay

*Correspondence: [e-mail].

Abstract

Case Presentation: AJAS, 3 years old, referred to the neuropediatrics clinic due to global delay in neuropsychomotor development, uncoordinated movements and tremor. Investigated with imaging tests she presented with basal ganglia lesions in addition to a lactate peak in spectroscopy suggestive of Leigh Syndrome. Genetic panel for Leukodystrophies was performed with identification of two novel mutations of uncertain clinical significance interpreted as combined heterozygosity in the GFM2 gene on chromosome 5q13 (p.His539Asn and p.Thr84_Thr87del), related to Combined Deficiency in oxidative phosphorylation-39 (OMIM #618397). During the investigation, the family pointed to a 14-year-old sister with a history of similar delay, but of unknown etiology so far, revised tomography with similar alterations, now awaiting genetic investigation.

Discussion: Combined oxidative phosphorylation-39 deficiency (COXPD-39) is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. According to three studies from the Online Mendelian Inheritance in Man (OMIM), affected patients have global developmental delay or regression, axial hypotonia with limb spasticity or other movement disorders and intellectual disability. In some cases, there are also seizures and features of Leigh's syndrome on brain scans. Currently, there are no standardized therapeutic protocols for the treatment of patients with oxidative phosphorylation disorders and treatment may vary between specialized centers. Coenzyme Q10 is often a constituent of this treatment as it serves as an antioxidant and restores electron flow in mitochondrial respiration.

Final Comments: There are variable deficiencies of the enzyme complexes of the mitochondrial respiratory chain in the tissues of patients, with different degrees of impairment. There are few reports and research to clarify not only the mechanisms of mitochondrial disease at cellular and tissue levels, but also to determine the phenotypes and acknowledge every pathological mutations of this disorder and others related to mitochondrial translation factor genes.

 

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Publication History

Article published online:
12 May 2025