1. Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature

Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature

Krystyna Szymańska, PhD 1, 2 Agnieszka Ługowska, MD 3 Milena Laure-Kamionowska, PhD 1 Monika Bekiesińska-Figatowska, PhD 4 Dorota Gieruszczak-Białek, MD 2 Małgorzata Musielak, PhD 3 Sabrina Eichler, PhD 5 Anne Katrin Giese, MD 6 Prof. Arndt Rolfs, MD 5, 6
1 Polish Academy of Sciences Warsaw 2 Medical University of Warsaw 3 Institute of Psychiatry and Neurology Warsaw 4 Institute of Mother and Child Warsaw 5 CENTOGENE AG 6 University of Rostock
August 30, 2012

Folia Neuropathol 2012; 50 (4): 346-356
DOI: 10.5114/f n.20 12.323 64 

Globoid cell leukodystrophy (GLD, also known as Krabbe disease), whose pathophysiology is still not completely elucidated, is an inherited, metabolic, and neurodegenerative disease, caused by the deficiency of β-galactocerebrosidase (GALC) or in very rare cases by lack of active saposin A. We describe two patients, in whom first MRI changes were not suggestive of GLD. Additionally, in Patient 1, the residual β-galactocerebrosidase activity was rather high leading to difficulties in the diagnosing process. Molecular analysis of the GALC and PSAP genes in Patient 1, and of the GALC gene in Patient 2 confirmed the diagnosis of Krabbe disease. We have detected a novel mutation in the GALC gene in Patient 2, a deletion in exon 16, leading to the STOP codon (c.1851delT, p.Y617X). This deletion interrupts the reading frame prematurely: codon 617 is replaced by a STOP codon. A careful clinical description of presented patients is followed by a discussion of radiological, biochemical, genetic, and neuropathological studies. It concludes with a discussion of the potential difficulties encountered when diagnosing patients with rare diseases. In Patient 1 the postmortem examination of CNS revealed the presence of globoid cells grouped in multiple clusters seen in the white matter near the vessels. We would like to emphasize that proper clinical-radiological-biochemical co-operation and exchange of information between parents and specialists is a key issue in the diagnossis of rare and difficult neurological diseases, in particular, if the clinical picture is inconclusive.