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Título

NEURODEGENERATIVE DISEASE CAUSED BY THE TRAPPC4 GENE

Apresentação do caso

Female, 5 years old, daughter of a non-consanguineous couple, with pregnancy history of toxoplasmosis seroconversion but no perinatal complications and negative newborn screening tests. She had adequate neuropsychomotor development up to three months of age, when she began to experience milestones regression and acquired microcephaly, accompanied by hearing lossand movement disorders. At first evaluation, she had microcephaly, poor eye fixation, axial hypotonia and appendicular hypertonia, global hyperreflexia, myoclonus and generalized dystonias. No dysmorphisms were noted. She has undergone extensive diagnostic investigation, with: metabolic acidosis, hyperlactatemia, plasma amino acid chromatography with increased glycine. Toxoplasmosis serology was non-reactive and the results of ammonia, urinary organic acids and mucopolysaccharides, enzyme assays (arylsulfatase A, beta-galactosidase and palmitoyl-protein thioesterase 1), lymphocytes inclusions research and molecular panel for epilepsies were all normal. Electroneuromyography was normal and electroencephalogram showed low-amplitude tracing. Cranial MRI (2018) presented important diffuse reduction of brain parenchyma, hypersignal on T2 and FLAIR in the remaining parenchyma with thinning of the corpus callosum; Cranial MRI (2021) showed progressive worsening of cerebral parenchyma atrophy and T2 hypersignal in bilateral subcapsular thalamic region, trunk and cerebellum. The diagnosis was confirmed by exome sequencing with the homozygous pathogenic variant in the TRAPPC4 c.454+3A>G;p(?) gene. Our patient showed improvement of abnormal movements after using levetiracetam.

Discussão

The TRAPPC4 gene synthesizes one of the proteins that form the TRAPPcomplex, which hasthe function of regulating the transport of vesicles between endoplasmic reticulum and Golgi complex, besides secretion and cellular autophagy. Pathogenic variants in the TRAPPC4 gene cause an autossomal recessive developmental disorder with epilepsy, spasticity and cerebral atrophy. Epilepsy has an early onset, associated with microcephaly, dysmorphisms, hearing loss, visual alteration and movement disorders. Skull MRI shows cerebral atrophy, reduced white matter and cerebellar atrophy.

Comentários finais

This entity is rare, with few cases described in recent literature. Next-generation sequencingis critical for diagnosis and enables genetic counseling.

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Área

Neurogenética