Dados do Trabalho

Título

MUTATION IN THE PIGA GENE: REPORT OF A RARE PEDIATRIC CASE

Apresentação do caso único

Male, 3 years old. Second pregnancy of a non-consanguineous couple, uneventful. Full term, early jaundice. At 2 years of age, he started having epileptic seizures characterized by mydriasis, sialorrhea, and short-lasting masticatory automatisms. Medical evaluation:symmetrical skull but facial dysmorphisms(low-set ears and folded helix, broad forehead, anteverted nose), axial and appendicular hypotonia. Global developmental delay and difficulty in oral feeding. Neuroimaging showed volumetric reduction and areas of apparent signal alteration compromising the central/deep white matter adjacent to the lateral ventricles, diffuse thinning of the corpus callosum, in addition to involvement of the hippocampal formations and compensatory ectasia of the supratentorial ventricular system. Electrophysiological examination revealed frequent focal epileptiform discharges of sharp waves and spikes in multifocal projection, predominantly in the right middle temporal region. Abdominal ultrasound noted duplication of the left renal collecting system. In the genetic investigation with next-generation sequencing-Exome, which found a pathogenic variant in hemizygosity of the PIGA gene. To date, he is being monitored for drug-resistant epilepsy, using valproate, topiramate, clobazam, cannabidiol and lastly a ketogenic diet. He was referred to the Pediatric Surgery team due to the need for feeding via an alternative route.

Discussão

Multiple congenital anomalies-hypotonia-seizures syndrome-2(MCAHS2) is a rare disease caused by a mutation in the PIGAgene, inherited recessively on the X-linked chromosome Xp22.2. The class A phosphatidylinositol glycan (PIGA) protein plays a role in the glycosylphosphatidylinositol anchoring pathway in many blood cells and serves to anchor proteins to the cell surface. It is believed that the mutation causes the protein to become functionally residual, allowing for a certain survival. Clinically, manifests as neurodevelopmental disorder, neonatal hypotonia, early-onset myoclonic seizures, and variable congenital anomalies involving the cardiac and urinary systems. Similar to case, is described that patients present with early-onset epileptic encephalopathy associated with developmental arrest and severe neurological deficiency. The ketogenic diet has been successfully used in the treatment of refractory epilepsy, especially in children.

Comentários finais

This report highlights the importance of early diagnosis, therapeutic ketogenic diet and multidisciplinary follow-up.

Referências

1. Shemansky JM, McDaniel LP, Klimas C, Dertinger SD, Dobrovolsky VN, Kimoto T, Horibata K, Polli JE, Heflich RH. Pig-a gene mutation database. Environ Mol Mutagen. 2019 Oct;60(8):759-762. doi: 10.1002/em.22298. Epub 2019 Jun 7. PMID: 31090953.
2. Belet S, Fieremans N, Yuan X, Van Esch H, Verbeeck J, Ye Z, Cheng L, Brodsky BR, Hu H, Kalscheuer VM, Brodsky RA, Froyen G. Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. Hum Mutat. 2014 Mar;35(3):350-5. doi: 10.1002/humu.22498. Epub 2014 Jan 13. PMID: 24357517.

Palavras Chave

PIGA; epilepsy; intellectual disability;