Familial global developmental delay secondary to β-mannosidosis

Gowda, Vykuntaraju K; Nagarajan, Balamurugan; Suryanarayana, Srividya G.; Srinivasan, Varunvenkat M.

doi:10.4103/jpn.jpn_65_20

Cited by 2 publications

(1 citation statement)

References 6 publications

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“…WES revealed a rare homozygous variant of uncertain significance in MANBA [NM_005908.4(MANBA):c.519G > T (p.Lys173Asp)], which is associated with beta mannosidosis; however, she did not have hepatosplenomegaly and urine oligosaccharides returned as normal, ruling out the diagnosis of beta mannosidosis (Gowda et al ., 2021). She then underwent WGS, which revealed a homozygous variant in DEGS1 [NM_003676.4(DEGS1): c.565A > G (p.Asn189Asp)] (ClinVar accession: VCV000805860.3), while both parents were heterozygous for the same variant.…”

Section: Resultsmentioning

confidence: 99%

DEGS1-related leukodystrophy: a clinical report and review of literature

Wong

Thomas

Lim

et al. 2023

Clinical Dysmorphology

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Background: Leukodystrophies are a heterogeneous group of disorders affecting the white matter of the central nervous system, with or without affecting the peripheral nervous system. Biallelic variants in DEGS1, coding for desaturase 1 (Des1) protein, were recently reported to be associated with hypomyelinating leukodystrophy (HLD), a subclass of leukodystrophies where the formation of the myelin sheath is affected.Methods Genomic sequencing was performed on our index patient with severe developmental delay, severe failure to thrive, dystonia, seizures, and hypomyelination on brain imaging. Sphingolipid analysis was performed and dihydroceramide/ceramide (dhCer/Cer) ratios were obtained by the measurement of ceramide and dihydroceramide species.Results A homozygous missense variant was identified in DEGS1 (c.565A > G:p Asn189Asp). The identified DEGS1 variant has been annotated as "conflicting reports of pathogenicity" on ClinVar. Follow-up sphingolipid analysis on our patient showed significantly raised dhCer/ Cer and this was consistent with dysfunction of the Des1 protein, providing additional evidence to support the pathogenicity of this variant. ConclusionWhile rare, pathogenic variants in DEGS1 should be considered in patients with HLD phenotype. To date, 25 patients have been reported across four studies on DEGS1-related HLD, and, in this report, we summarize the literature. More such reports will enable deeper phenotypic characterization of this disorder.

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Section: Resultsmentioning

confidence: 99%

DEGS1-related leukodystrophy: a clinical report and review of literature

Wong

Thomas

Lim

et al. 2023

Clinical Dysmorphology

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Lysosomal Dysfunction: Connecting the Dots in the Landscape of Human Diseases

Uribe-Carretero,

Rey,

Fuentes

et al. 2024

Biology

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Lysosomes are the main organelles responsible for the degradation of macromolecules in eukaryotic cells. Beyond their fundamental role in degradation, lysosomes are involved in different physiological processes such as autophagy, nutrient sensing, and intracellular signaling. In some circumstances, lysosomal abnormalities underlie several human pathologies with different etiologies known as known as lysosomal storage disorders (LSDs). These disorders can result from deficiencies in primary lysosomal enzymes, dysfunction of lysosomal enzyme activators, alterations in modifiers that impact lysosomal function, or changes in membrane-associated proteins, among other factors. The clinical phenotype observed in affected patients hinges on the type and location of the accumulating substrate, influenced by genetic mutations and residual enzyme activity. In this context, the scientific community is dedicated to exploring potential therapeutic approaches, striving not only to extend lifespan but also to enhance the overall quality of life for individuals afflicted with LSDs. This review provides insights into lysosomal dysfunction from a molecular perspective, particularly in the context of human diseases, and highlights recent advancements and breakthroughs in this field.

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Familial global developmental delay secondary to β-mannosidosis

Cited by 2 publications

References 6 publications

DEGS1-related leukodystrophy: a clinical report and review of literature

DEGS1-related leukodystrophy: a clinical report and review of literature

Lysosomal Dysfunction: Connecting the Dots in the Landscape of Human Diseases

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