title: Clinical and molecular report of novel GALC mutations in Moroccan patient with Krabbe disease: case report.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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*.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. maria.zerkaoui@gmail.com.|Département de Génétique Médical, Institut National d'Hygiène, Rabat, Morocco. maria.zerkaoui@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Zerkaoui
authors.affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. i.ratbi@um5s.net.ma.
authors.forename: I
authors.initials: I
authors.lastname: Ratbi
authors.affiliation: Unità di Genetica delle Malattie Neurodegenerative e Metaboliche, Dipartimento di Diagnostica e Tecnologia Applicata, Fondazione IRCCS -Istituto Neurologico Carlo Besta, Milan, Italy. bcastellotti@istituto-besta.it.
authors.forename: B
authors.initials: B
authors.lastname: Castellotti
authors.affiliation: Unità di Genetica delle Malattie Neurodegenerative e Metaboliche, Dipartimento di Diagnostica e Tecnologia Applicata, Fondazione IRCCS -Istituto Neurologico Carlo Besta, Milan, Italy. gellera@istituto-besta.it.
authors.forename: C
authors.initials: C
authors.lastname: Gellera
authors.affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. jaber.lyahyai@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Lyahyai
authors.affiliation: Unité de Neurologie Pédiatrique de Maladies Métaboliques, Service de Pédiatrie IIA, Hopital d'Enfant, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. dr.kriouile@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Kriouile
authors.affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. sefianigen@hotmail.com.|Département de Génétique Médical, Institut National d'Hygiène, Rabat, Morocco. sefianigen@hotmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Sefiani
mesh_terms: D005698:Galactosylceramidase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007223:Infant; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics*; D008297:Male; D009018:Morocco; D017354:Point Mutation
chemical_list: D005698:Galactosylceramidase