We present the case of an 18-month-old male with clinical and radiological findings concerning for Krabbe disease who had preserved GALC enzyme activity and negative GALC gene sequencing, but was found to have a homozygous variant, c.257 T > A (p.I86N), in the saposin A peptide of PSAP.
Development of a newborn screening tool based on bivariate normal limits: using psychosine and galactocerebrosidase determination on dried blood spots to predict Krabbe disease.
Globoid cell leukodystrophy or Krabbe disease is an autosomal recessive lysosomal storage disorder characterized by a deficiency in galactosylceramidase (GALC) which hydrolyses galactosylceramide and galactosylsphingosine (psychosine).
These defects were rescued by exposure to a lysosomal re-acidifying drug discovered in our studies on KD, and which provides multiple clinically relevant benefits in the twitcher (GALC<sup>+/-</sup>) mouse model of KD.
Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase.
We report a global adeno-associated virus (AAV)9-based gene therapy protocol to deliver therapeutic galactosylceramidase (GALC), a lysosomal enzyme that is deficient in Krabbe's disease.
Krabbe disease (KD), or globoid cell leukodystrophy, is an inherited lysosomal storage disease with leukodystrophy caused by a mutation in the galactosylceramidase (GALC) gene.
In this study, we hence investigated whether the UPR is activated in Krabbe disease using COS-7 cells expressing pathogenic GALC mutants and skin fibroblasts (SFs) from Krabbe disease patients with various phenotypes, using a combination of semiquantitative and quantitative real-time polymerase chain reactions.
Studying a skin biopsy, cultured fibroblasts showed the GALC activity at 21 to 30% of the normal level; ultrastructurally, clearly KD-specific inclusions were seen in the eccrine sweat gland cells, confirming a KD diagnosis.
GALC is inactivated also in the Twitcher (TWI) mouse: a genetic model of KD that is providing important insights into the understating of the pathogenetic process and the development of possible treatments.