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A novel variant of GALC in a familial case of Krabbe disease: Insights from structural bioinformatics and molecular dynamics simulation

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A novel variant of GALC in a familial case of Krabbe disease: Insights from structural bioinformatics and molecular dynamics simulation

Ikram Ullah
Muhammad Waqas
Muhammad Ilyas
Sobia Ahsan Halim
Akmal Ahmad
Natalia Dominik
Wahid Ullah
Muhammad Abbas
Muhammad Aamir
SYNaPS Study Group
Queen Square Genomics
Henry Houlden
Stephanie Efthymiou
Ajmal Khan
Ahmed Al-Harrasi
Genes & Diseases第10卷, 第6期pp.2263-2266纸质出版 2023-11-01在线发表 2023-04-23
126703

Krabbe disease or globoid cell leukodystrophy (GLD; MIM#245200) is a rare and fatal lysosomal storage disease with an autosomal recessive mode of inheritance that results from the deficiency of galactocerebrosidase (GALC; E.C. 3.2.1.46), a lysosomal enzyme encoded by the GALC gene. GALC breaks down galactosylceramide, a cerebroside located mainly in the myelin sheath. Defects in GALC cause the accumulation of a cytotoxic metabolite, galactosylsphingosine or psychosine, which can be toxic to oligodendrocytes and Schwann cells. The failure to digest galactosylceramide triggers the formation of multi-nucleated globoid cells, causing severe demyelination, axonopathy, and neuronal death. The reported frequency of Krabbe disease is 1 in 100,000 live births with symptoms including irritability, loss of motor ability, spasticity, ataxia, visual dysfunction, seizures, and cognitive impairment.

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