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

Zerkaoui M, Ratbi I, Castellotti B, Gellera C, Lyahyai J, Kriouile Y, Sefiani A - BMC Pediatr (2015)

Bottom Line: Disorder's onset is characterized, in early childhood, by hyperirritability, psychomotor deterioration associated to episodes of fever.Galactocerebrosidase deficiency was confirmed by biochemical analysis.The identification of these mutations and their associated phenotypes are important to predict the prognosis and to confer to families an adequate genetic counseling.

View Article: PubMed Central - PubMed

Affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. maria.zerkaoui@gmail.com.

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.

Case presentation: 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*.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

DNA sequencing of the patient showed two novel GALC gene mutations, c.860G>A inherited from his mother and c.1622G>A inherited from his fatherᅟ
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Fig1: DNA sequencing of the patient showed two novel GALC gene mutations, c.860G>A inherited from his mother and c.1622G>A inherited from his fatherᅟ

Mentions: In our clinical case, The onset of the disease was early in the 4th months of life. The disease’s evolution has been so fast that when we examined the patient on the 5th month, he was entirely hypotonic and already experienced feeding difficulty. Proband’s GALC enzyme activity was slightly decreased. This evolution is compatible with infantile form, which motivated us to seek the deletion of 30Kb by real time PCR. Once we observed that there was no such deletion, we opted for the complete sequencing of the gene. This method revealed that our patient was heterozygous compound for the mutations c.860G > A (p.Cys287Tyr) and c.1622G > A (p.Trp541*) (Fig.1).


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

Zerkaoui M, Ratbi I, Castellotti B, Gellera C, Lyahyai J, Kriouile Y, Sefiani A - BMC Pediatr (2015)

DNA sequencing of the patient showed two novel GALC gene mutations, c.860G>A inherited from his mother and c.1622G>A inherited from his fatherᅟ
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4644339&req=5

Fig1: DNA sequencing of the patient showed two novel GALC gene mutations, c.860G>A inherited from his mother and c.1622G>A inherited from his fatherᅟ
Mentions: In our clinical case, The onset of the disease was early in the 4th months of life. The disease’s evolution has been so fast that when we examined the patient on the 5th month, he was entirely hypotonic and already experienced feeding difficulty. Proband’s GALC enzyme activity was slightly decreased. This evolution is compatible with infantile form, which motivated us to seek the deletion of 30Kb by real time PCR. Once we observed that there was no such deletion, we opted for the complete sequencing of the gene. This method revealed that our patient was heterozygous compound for the mutations c.860G > A (p.Cys287Tyr) and c.1622G > A (p.Trp541*) (Fig.1).

Bottom Line: Disorder's onset is characterized, in early childhood, by hyperirritability, psychomotor deterioration associated to episodes of fever.Galactocerebrosidase deficiency was confirmed by biochemical analysis.The identification of these mutations and their associated phenotypes are important to predict the prognosis and to confer to families an adequate genetic counseling.

View Article: PubMed Central - PubMed

Affiliation: Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. maria.zerkaoui@gmail.com.

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.

Case presentation: 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*.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus