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Título

A CASE REPORT OF TWO NOVEL MUTATIONS SUGGESTIVE OF COMBINED DEFICIENCY OF OXIDATIVE PHOSPHORYLATION-39 (COXPD-39) IN A PATIENT WITH GLOBAL DEVELOPMENT DELAY.

Apresentação do caso

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.

Discussão

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 is 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.

Comentários finais

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.

Referências (se houver)

Glasgow, RIC, Thompson, K., Barbosa, IA, He, L., Alston, CL, Deshpande, C., Simpson, MA, Morris, AAM, Neu, A., Lobel, U., Hall, J., Prokisch, H., Haack, TB, Hempel, M., McFarland, R., Taylor, RW Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits. Neurogenetics 18: 227-235, 2017.

Dixon-Salazar TJ, Silhavy JL, Udpa N., Schroth J., Bielas S., Schaffer AE, Olvera J., Bafna V., Zaki MS, Abdel-Salam GH, Mansour , LA, Selim, L., and 17 others. Exome sequencing can improve diagnosis and change patient management. science Trans. Med. 4: 138ra78, 2012. Note: Electronic article.

Palavras Chave

COMBINED DEFICIENCY OF OXIDATIVE PHOSPHORYLATION-39 (COXPD-39)

Declaração de conflito de interesses de TODOS os autores

Não há conflito de interesses