Metachromatic leukodystrophy (MLD) is the typical white matter disease belonging to the lysosomal sphingolipid storage group and is a genetic autosomal recessive disorder. Early presentation is in the form of learning disability and behavioral issues; the subsequent involvement is gait and balance. Prenatal blood testing for genetic screening is available for arylsulfatase A (ARSA) deficiency is indicated if the family history is positive for MLD. Diagnostic tools for MLD are- absence or low-level arylsulfatase activity in genetic screening, sulphatides in urine, and magnetic resonance image (MRI) showing frontal horns and atrial periventricular leukodystrophy. The typical finding is known as the trigonid pattern. A two and half-year-old boy was born out of marriage in near blood relation. No prenatal screening was done. As narrated by the mother, the patient was alright six months back when he gradually developed lower limb weakness. Due to this, he stopped walking, which he could initially do without support. The parent also complained that he used to speak fifteen to twenty words, and now he is not saying a single word. With the above complaint, the patient was taken to the local hospital, where an MRI showed periventricular leukodystrophy, suggesting metachromatic leukodystrophy of periventricular white matter. The practice of prenatal and newborn genetic screening could enhance the efficacy of management, as early interventions are more effective.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885241 | PMC |
http://dx.doi.org/10.7759/cureus.33155 | DOI Listing |
J Inherit Metab Dis
January 2025
Department of Life Sciences, Manchester Metropolitan University, Manchester, UK.
There are currently at least 70 characterised lysosomal storage diseases (LSD) resultant from inherited single-gene defects. Of these, at least 30 present with central nervous system (CNS) neurodegeneration and overlapping aetiology. Substrate accumulation and dysfunctional neuronal lysosomes are common denominator, but how variants in 30 different genes converge on this central cellular phenotype is unclear.
View Article and Find Full Text PDFBiochem Genet
January 2025
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by mutations in the arylsulfatase A (ARSA) gene. Few studies have assessed the spectrum of ARSA mutations among Iranian patients. Here, we report eight Iranian patients with clinical features of MLD.
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 PDFFront Biosci (Schol Ed)
December 2024
Biochemical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, 12622 Cairo, Egypt.
Background: Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary neurodegenerative disease caused by a deficiency in arylsulfatase A (ARSA) activity and belongs to the group of lysosomal storage diseases. A biochemical diagnosis of MLD is based on determining the residual ARSA activity in leukocytes, skin fibroblasts, and urine. This study documents our biochemical experience and estimates the relative frequency of MLD over 21 years (2001-2022).
View Article and Find Full Text PDFMol Genet Metab
January 2025
The Children's Hospital of Philadelphia, Neurology, 3401 Civic Center Blvd, Philadelphia 19104, PA, USA. Electronic address:
Metachromatic leukodystrophy (MLD) is a progressive demyelinating disorder resulting from the toxic accumulation of sulfatides. The stereotyped neurodegeneration of MLD is well understood, and cases are categorized into subtypes by age at neurologic onset: late infantile (LI), juvenile (J), and adult. The systemic burden of disease, such as gallbladder involvement, however, is less well characterized.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!