PP03.13 – 2568: Two further Greek cases of Krabbe disease and a new mutation in the GALC gene

Abstract

Objective Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme galactocerebrosidase (GALC) and is classified into infantile and late-onset form, depending on the age of onset. Methods and results We report two Greek patients with Krabbe disease with the infantile and late-infantile forms, respectively. The first patient was admitted at the age of 3.5 months, due to generalized hypertonia and developmental delay. A brain MRI demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. A severe reduction in â-galactocerebrosidase activity (0.003 nmol/mg protein/hr, normal range 0.1–0.97 units), indicated the diagnosis of Krabbe disease, which was confirmed by molecular genetic testing (an homozygous c.411_413delTAA [K139del] mutation in the GALC gene). The second patient manifested with psychomotor regression at the age of 6 months, while the brain MRI was normal. At the age of 18 months, a repeated brain MRI demonstrated leukodystrophic changes, whereas NCVs were significantly delayed, too. A total lack of â-galactoserebrosidase activity (0.00 nmol/mg protein/hr, normal range 0.1–0.97 units) led to further molecular genetic testing, which revealed a homozygous c.749T>C [p.I250T] mutation in the GALC gene. At their last follow-up visit at the age of 4 and 10 years, respectively, both patients were bed-ridden and demonstrated the clinical picture of spastic tetraplegia suffering from frequent infections of the respiratory tract and fed through a gastrostomy catheter. Conclusion The c.411_413delTAA [K139del] mutation is the first reported in the literature, while there are another two reports of patients bearing the c.749T>C [p.I250T] mutation. Interestingly, both these patients were of Greek ancestry, a fact that could be indicative of a founder effect. Genotyping of patients of Krabbe disease is important, in order to contribute to a European mutation database and to further study possible genotype-phenotype correlations.