A novel homozygous GALC variant has been associated with Krabbe disease in a consanguineous family

Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal storage disorder involving the white matter of the peripheral and the central nervous systems. It is caused by a deficiency of galactocerebrosidase enzyme activity. The most common manifestation is the classical e...

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Bibliographic Details
Published in:Neurological sciences 2018-12, Vol.39 (12), p.2123-2128
Main Authors: Tuncer, Feyza Nur, Iseri, Sibel Aylin Ugur, Yapici, Zuhal, Demir, Mahmut, Karaca, Meryem, Calik, Mustafa
Format: Article
Language:English
Subjects:
Children
Diagnosis
EEG
Enzymatic activity
Genetic counseling
Genetic screening
Hereditary diseases
Leukodystrophy
Magnetic resonance imaging
Medicine
Medicine & Public Health
Neuroimaging
Neurology
Neuroradiology
Neurosciences
Neurosurgery
NMR
Nuclear magnetic resonance
Original Article
Psychiatry
Substantia alba
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Description
Summary:Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal storage disorder involving the white matter of the peripheral and the central nervous systems. It is caused by a deficiency of galactocerebrosidase enzyme activity. The most common manifestation is the classical early onset KD that leads to patient’s loss before the age of 2. Herein, we report the evaluation of a consanguineous family with three affected children manifesting severe neurological findings that ended with death before the age of 2, in an attempt to provide genetic diagnosis to the family. One of the children underwent detailed physical and neurological examinations, including brain magnetic resonance imaging (MRI) and scalp electroencephalography (EEG) evaluations. GALC genetic testing on this child enabled identification of a novel homozygous variant (NM_000153.3: c.1394C>T; p.(Thr465Ile)), which confirmed diagnosis as KD. Familial segregation of this variant was performed by PCR amplification and Sanger sequencing that revealed the parents as heterozygous carriers. We believe this novel GALC variant will not only help in genetic counseling to this family but will also aid in identification of future KD cases.
ISSN:1590-1874
1590-3478
DOI:10.1007/s10072-018-3556-2