Cases of metachromatic leucodystrophy in brother and sister are presented. The clinical pattern in the female was characterised by the progressing dementia, whereas in the male the first symptom was the manic syndrome. The neurological status was normal. The cases were diagnosed by the demyelination visible in MRI pattern and in the decreased activity of arylsulphatase A in blood leukocytes.
Download full-text PDF |
Source |
---|
Hum Genet
January 2025
TCS Research, Tata Consultancy Services, Hyderabad, India.
Variants of uncertain significance (VUS) represent variants that lack sufficient evidence to be confidently associated with a disease, thus posing a challenge in the interpretation of genetic testing results. Here we report an improved method for predicting the VUS of Arylsulfatase A (ARSA) gene as part of the Critical Assessment of Genome Interpretation challenge (CAGI6). Our method uses a transfer learning approach that leverages a pre-trained protein language model to predict the impact of mutations on the activity of the ARSA enzyme, whose deficiency is known to cause a rare genetic disorder, metachromatic leukodystrophy.
View Article and Find Full Text PDFGenes (Basel)
November 2024
Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain.
(1) Background: Most rare disease patients endure long delays in obtaining a correct diagnosis, the so-called "diagnostic odyssey", due to a combination of the rarity of their disorder and the lack of awareness of rare diseases among both primary care professionals and specialists. Next-generation sequencing (NGS) techniques that target genes underlying diverse phenotypic traits or groups of diseases are helping reduce these delays; (2) Methods: We used a combination of biochemical (thin-layer chromatography and high-performance liquid chromatography-tandem mass spectrometry), NGS (resequencing gene panels) and splicing assays to achieve a complete diagnosis of three patients with suspected metachromatic leukodystrophy, a neurologic lysosomal disorder; (3) Results: Affected individuals in each family were homozygotes for harmful variants in the gene, one of them novel (c.854+1dup, in family 1) and the other already described (c.
View Article and Find Full Text PDFInt J Surg Case Rep
January 2025
Debre Markos University, Surgery Department, Ethiopia. Electronic address:
Metachromatic leukodystrophy (MLD) is a genetic lysosomal disease. Here, we investigated the role of prosaposin () gene mutations in MLD. This current case report describes a female patient who presented with motor development regression at two years and five months of age.
View Article and Find Full Text PDFJ Child Neurol
January 2025
Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
RNA polymerase III (POLR3)-related leukodystrophy is a rare, neurodegenerative disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. Despite the challenges of caring for a child with POLR3-related leukodystrophy, few studies have examined parents' disease burden. We sought to investigate quality of life and stress levels amongst parents of children with POLR3-related leukodystrophy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!