Dados do Trabalho

Título

MITOCHONDRIAL SHORT-CHAIN ENOYL-COA HYDRATASE 1 DEFICIENCY: A RARE CAUSE OF LEIGH SYNDROME

Apresentação do caso único

A 6 months-old girl presents to a routine primary care consult with a neurodevelopmental arrest and plateauing of head circumference curve. Rapidly referred to a specialized evaluation, the child neurologists observe brief and sudden forward movements of the body, as well as stiffening of the arms and legs, lasting for one to two seconds. An infantile epileptic spasms syndrome diagnosis is carried out, with brain imaging demonstrating extensive areas of restricted diffusion and hyperintense signal on T2, bilaterally and symmetrically affecting predominantly the subcortical hemispheric white matter, the globi pallidi, the substantia nigra, the decussation and superior cerebellar peduncles, the white matter around the cerebellar dentate nuclei, the central tegmental tract and the inferior cerebellar peduncles. Proton spectroscopy showed reduction in N-acetyl aspartate (NAA) peak, signaling neuroaxonal dysfunction. Whole exome sequencing unraveled biallelic pathogenic variants in the gene ECHS1, confirming the mitochondrial short-chain enoyl-CoA hydratase 1 deficiency as the neurodegenerative disorder implied to the case.

Discussão

Leigh syndrome (LS) is a progressive neurodegenerative disorder, generally presented between the ages of three and twelve months. To date, more than 110 different genes have been described as causative models of LS. In humans, most of these genes are found in the nuclear DNA, albeit mitochondrial DNA (mtDNA) may also be implicated in about 20% of cases. Although involved in the mitochondrial oxidative phosphorylation pathway, ECHS1 deficiency is inherited in an autosomal recessive manner. Its severe course is marked upon neurological impairment, such as serious encephalopathy and pyramidal and extrapyramidal symptoms. A concurrent multisystemic involvement is expected, with emphasis on failure to thrive (62% of cases), cardiomyopathy (60%) and lactic acidemia (75%).

Comentários finais

A subtle onset of developmental arrest, with marked complex neurological display and multisystemic involvement should prompt the caregiver to hypothesize a mitochondrial disorder. Brain imaging shows T2-hyperintense lesions in the basal ganglia, the putamina and thalami in particular, rarely involving cerebral and cerebellar white matter and the spinal cord.

Referências

1. Ganetzky R, Stojinski C. Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency. 2019 Jun 20. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.
2. BMC Neurol. 2018; 18: 99

Palavras Chave

Leigh syndrome; Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency; Mitochondriopathies