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

• Published in: BMC neurology Vol. 19; no. 1; p. 122
• Main Authors: Zhuang, Shunzhi, Kong, Lingen, Li, Caiming, Chen, Likun, Zhang, Tingting
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.06.2019; BioMed Central; BMC
• Subjects: Age; Biochemical analysis; Brain MRI; Brain research; Care and treatment; Case Report; Case reports; Case studies; Causes of; Demyelination; Diagnosis; Diagnostic imaging; DNA; DNA sequencing; Enzymes; Families & family life; Gait; Galactocerebrosidase; Galactosylceramidase; Galactosylceramide; GALC gene; Genes; Genetic aspects; Genotype & phenotype; Globoid cell leukodystrophy; Krabbe disease; Late-onset; Leukodystrophy; Magnetic resonance imaging; Movement disorders; Mutation; Nervous system diseases; Neurodegenerative diseases; Neuroimaging; Paraplegia; Patients; Pyramidal tracts; Spastic paraplegia; Spinal cord; Substantia alba; Visual impairment; Vitamin B; China; Brain MRI; GALC gene; Galactocerebrosidase; Krabbe disease; Late-onset
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-019-1345-z

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