Authors present a case of mucolipidosis III diagnosed in a boy suffering from articular retractions, platyspondylia and a normal mucolysacchariduria. Biochemical characteristics of the lisosomial enzyme, reduced in fibroblasts in culture and increased in biological fluids allow such diagnose. Primary enzyme lack being not yet explained, authors comment upon the hypothesis trying to explain biochemical findings.
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Genes (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 PDFBMC Pediatr
December 2024
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, China.
Background: Mucolipidosis (ML) II and III alpha/beta are lysosomal disorders caused by mutations in the GNPTAB gene which encodes the alpha and beta subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase.
Method: To explore the clinical and molecular characteristics of the 20 ML II and III alpha/beta patients, clinical data was collected and GNPTAB gene was analyzed by nest PCR and direct Sanger-sequencing. The activity of several lysosomal enzymes was measured in the plasma.
Orphanet J Rare Dis
November 2024
Department of Endocrinology, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health, Genetics, Metabolism, Beijing, 100045, China.
Ann Clin Transl Neurol
November 2024
Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, 350005, China.
Mol Genet Metab
November 2024
Greenwood Genetic Center, Greenwood, SC 29646, United States of America. Electronic address:
Defining the molecular consequences of lysosomal dysfunction in neuronal cell types remains an area of investigation that is needed to understand many underappreciated phenotypes associated with lysosomal disorders. Here we characterize GNPTAB-knockout DAOY medulloblastoma cells using different genetic and proteomic approaches, with a focus on how altered gene expression and cell surface abundance of glycoproteins may explain emerging neurological issues in individuals with GNPTAB-related disorders, including mucolipidosis II (ML II) and mucolipidosis IIIα/β (ML IIIα/β). The two knockout clones characterized demonstrated all the biochemical hallmarks of this disease, including loss of intracellular glycosidase activity due to impaired mannose 6-phosphate-dependent lysosomal sorting, lysosomal cholesterol accumulation, and increased markers of autophagic dysfunction.
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