Endocrine Abstracts

Krabbe disease, also known as globoid cell leukodystrophy, is an autonomic recessive genetic disorder caused by GALC mutations. GALC gene codes for galactosylceramidase, which is a lysosomal enzyme. This disorder can occur during early childhood, between the ages of 1 and 8 years old (later onset form) or during adulthood; its prevalence is estimated at 1/100 000. Nevertheless, in most cases, this disorder occurs during childhood. With this case report, our aim is to attempt to describe both clinical features and evolution of this rare defect. A 5-year-old non-consanguineous female with a good psychomotor development has been showing psychomotor regression including generalised hypotonia, loss of both speech and walking since age 3. This patient no dysmorphia and no organomegaly and she had no fever. Genetic testing revealed the presence of a compound heterozygote mutation in GALC gene— c.865G>C and c.195G>C confirming diagnosis of globoid cell leukodystrophy. Both parents received genetic counselling in order to determine the risk of reiteration and to offer prenatal diagnosis in case of any future pregnancy. Regarding patients with later onset globoid cell leukodystrophy (occurrence between 1 and 8 years of age), as is the case we are currently reporting, initial symptoms usually include eating difficulties and irritability. Then hypertonic episodes including myoclonic seizures occur in association with development regression. During the final stage of this disorder, hypotonia, blindness and deafness appear. Diagnosis can be stablished based on reduced galactosylceramidase enzymatic activity or by genetic testing for mutations in GALC gene. Death usually occurs 2 to 7 years after initial symptoms begin. For patients with either early childhood or later onset forms of this disorder, the only therapeutic option is hematopoietic stem-cell transplantation which slows down development of this disease. These facts provide new light on the need for genetic cancelling in order to provide pre-symptomatic diagnosis to at risk relatives. Furthermore, reporting of new cases will help to better unravel the phenotype-genotype correlation of GALC gene variants.