Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report

• Published in: BMC pediatrics Vol. 15; no. 181; p. 182
• Main Authors: Zerkaoui, M, Ratbi, I, Castellotti, B, Gellera, C, Lyahyai, J, Kriouile, Y, Sefiani, A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.11.2015; BioMed Central
• Subjects: Age; Analysis; Care and treatment; Case Report; Case reports; Complications and side effects; Consent; Data analysis; Deoxyribonucleic acid; DNA; Enzymes; Families & family life; Galactosylceramidase - deficiency; Galactosylceramidase - genetics; Gene mutations; Genetic counseling; Genotype & phenotype; Globoid cell leukodystrophy; Humans; Infant; Leukodystrophy, Globoid Cell - genetics; Literature reviews; Male; Metabolism; Morocco; Mutation; Novels; Ostomy; Parents & parenting; Patients; Point Mutation; Proteins; Morocco
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/s12887-015-0490-9

Krabbe disease (KD) or globoid cell leukodystrophy is an autosomal recessive lysosomal disorder, which affects metabolic and neurologic systems. This pathology has different forms. Infantile onset is about 85% to 90% of individuals with Krabbe disease. Disorder's onset is characterized, in early childhood, by hyperirritability, psychomotor deterioration associated to episodes of fever. To date, all reported cases have been attributed to mutations in galactosylceramidase gene (GALC gene) that encodes an enzyme which degrades galactosyl-sphingolipids (galactosylceramide, psychosine), essential in myelin production. A child compounded with two new mutations in the GALC gene was detected. An eleven month old male child of Moroccan origin presented to our genetic consultation with severe symptoms that included hypotonia, fever, vision loss and feeding difficulties. He was suffering from the 4th month of life. Krabbe disease was suspected. Galactocerebrosidase deficiency was confirmed by biochemical analysis. DNA sequencing revealed a novel heterozygous compound mutation in GALC gene. The child was compounded with two mutations c.860G > A; p.Cys287Tyr and c.1622G > A; p.Trp541*. These new mutations could affect GALC structure and therefore its function. The identification of these mutations and their associated phenotypes are important to predict the prognosis and to confer to families an adequate genetic counseling.