Back to Search Start Over

PNPT1 Spectrum Disorders: An Underrecognized and Complex Group of Neurometabolic Disorders

Authors :
Paulo Sgobbi
Igor Braga Farias
Paulo de Lima Serrano
Bruno de Mattos Lombardi Badia
Hélvia Bertoldo de Oliveira
Alana Strucker Barbosa
Camila Alves Pereira
Vanessa de Freitas Moreira
Marco Antônio Troccoli Chieia
Adriel Rêgo Barbosa
Pedro Henrique Almeida Fraiman
Vinícius Lopes Braga
Roberta Ismael Lacerda Machado
Sophia Luiz Calegaretti
Isabela Danziato Fernandes
Roberta Correa Ribeiro
Marco Antonio Orsini Neves
Wladimir Bocca Vieira de Rezende Pinto
Acary Souza Bulle Oliveira
Source :
Muscles, Vol 3, Iss 1, Pp 4-15 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

An 18-year-old man presented with slowly progressive infancy-onset spasticity of the lower limbs and cerebellar ataxia, associated with painless strabismus, intellectual disability, urinary incontinence, bilateral progressive visual loss, and cognitive decline since early adolescence. A neurological examination disclosed spastic dysarthria, left eye divergent strabismus, bilateral ophthalmoparesis, impaired smooth pursuit, severe spastic paraparesis of the lower limbs with global brisk tendon reflexes, bilateral extensor plantar responses, and bilateral ankle clonus reflex. Bilateral dysdiadochokinesia of the upper limbs, Stewart-Holmes rebound phenomenon, bilateral dysmetria, and a bilateral abnormal finger-to-nose test were observed. Markedly reduced bilateral visual acuity (right side 20/150, left side 20/400) and moderate to severe optic atrophy were detected. Neuroimaging studies showed cerebellar atrophy and bilateral optic nerves and optic tract atrophy as the main findings. As a complicated Hereditary Spastic Paraplegia, autosomal dominant Spinocerebellar Ataxia, or inherited neurometabolic disorders were suspected, a large next-generation sequencing-based gene panel testing disclosed the heterozygous pathogenic variant c.162-1G>A in intron 1 of the PNPT1 gene. A diagnosis of PNPT1-related spastic ataxia was established. Clinicians must be aware of the possibility of PNPT1 pathogenic variants in cases of spastic ataxia and spastic paraplegias that are associated with optic atrophy and marked cognitive decline, regardless of the established family history of neurological compromise.

Details

Language :
English
ISSN :
28130413
Volume :
3
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Muscles
Publication Type :
Academic Journal
Accession number :
edsdoj.2a0b634e5cd440ce9ec3c9e42072fe9c
Document Type :
article
Full Text :
https://doi.org/10.3390/muscles3010002