Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 Jun 11;19(1):122.
doi: 10.1186/s12883-019-1345-z.

GALC mutations in Chinese patients with late-onset Krabbe disease: a case report

Shunzhi Zhuang  1 , Lingen Kong  1 , Caiming Li  2 , Likun Chen  1 , Tingting Zhang  1
Affiliations
Case Reports

GALC mutations in Chinese patients with late-onset Krabbe disease: a case report

Shunzhi Zhuang et al. BMC Neurol. .

Abstract

Background: Krabbe disease (also known as globoid cell leukodystrophy) cause by a deficiency of the enzyme β-galactocerebrosidase (galactosylceramidase, GALC). The deficiency of GALC leads to accumulation of galactosylceramide and psychosine, the latter GALC substrate having a potential role in triggering demyelination. Typically, the disease has an infantile onset, with rapid deterioration in the first few months, leading to death before the age of 2 years. The late onset forms (late-infantile, juvenile, and adult forms) are rare with variable clinical outcomes, presenting spastic paraplegia as the main symptom.

Case presentation: We recruited a family with two affected individuals. The proband (Patient 1), a 25-year-old male, was presented with slow progressive symptoms, including spastic gait disturbance and vision loss since the 5th year of life. His elder sister (Patient 2), became wheelchair-bound and demented at the age of 22 years. Brain magnetic resonance imaging (MRI) showed increased signal intensity in the white matter along with the involvement of the bilateral corticospinal tracts. GALC deficiency was confirmed by biochemical analysis. DNA sequencing revealed two mutations (c.865G > C: p. G289R and c.136G > T: p. D46Y) in GALC. The clinical characteristics, brain MRI, biochemical and molecular findings led to the diagnosis of Krabbe disease.

Conclusion: Clinical and neuroimaged signs, positive enzymatic analysis and molecular data converged to definite diagnosis in this neurodegenerative disease.

Keywords: Brain MRI; GALC gene; Galactocerebrosidase; Krabbe disease; Late-onset.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Molecular genetic analysis of the GALC gene showed the two mutations, c.865G > C inherited from the patients’ mother (a) and c.136G > T inherited from their father (b)
Fig. 2
Fig. 2
The sister was heterozygous for the GALC mutation c.865G > C (a) and heterozygous for c.136G > T (b)
Fig. 3
Fig. 3
Cerebral MR scans of the patient 1. The axial T2w and FLAIR image showed bilateral corticospinal tracts (a and c) and the left central gyrus cortex (b and d) signal hyperintensities. Cerebral T1w axial images (e) revealed a decreased signal in the left central gyrus cortex
Fig. 4
Fig. 4
Spinal T2w axial images (a and b) showed mild atrophy of spinal cord
Fig. 5
Fig. 5
Pedigree of the family
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Debs R, et al. Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review. J Inherit Metab Dis. 2013;36(5):859–868. doi: 10.1007/s10545-012-9560-4. - DOI - PubMed
    1. Hossain MA, et al. Late-onset Krabbe disease is predominant in Japan and its mutant precursor protein undergoes more effective processing than the infantile-onset form. Gene. 2014;534(2):144–154. doi: 10.1016/j.gene.2013.11.003. - DOI - PubMed
    1. Xu C, et al. Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype–phenotype correlation. J Hum Genet. 2006;51(6):548–554. doi: 10.1007/s10038-006-0396-3. - DOI - PubMed
    1. Tappino B, et al. Identification and characterization of 15 novel GALC gene mutations causing Krabbe disease. Hum Mutat. 2010;31(12):E1894–E1914. doi: 10.1002/humu.21367. - DOI - PMC - PubMed
    1. Kardas F, et al. A novel homozygous GALC mutation: very early onset and rapidly progressive Krabbe disease. Gene. 2013;517(1):125–127. doi: 10.1016/j.gene.2012.12.040. - DOI - PubMed

Publication types

Substances