Work

Natural History and Diagnostic Findings in an Adult Man Diagnosed With Attenuated Krabbe Disease

Year: 2025

Type: article

Abstract: Krabbe disease (KD), or globoid cell leukodystrophy, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency in galactocerebrosidase (GALC), leading to psychosine (galactosylsphingosine) accumulation and myelin damage. The natural history of the attenuated form is poorly understood, but it typically presents with spastic paraparesis, progressing more slowly than the early-onset or infantile variant. Diagnosis relies on a high index of clinical suspicion, imaging studies, biochemistry, and molecular analysis. Magnetic resonance imaging (MRI) demonstrates characteristic corticospinal tract involvement, while cerebrospinal fluid analysis can reveal elevated protein levels. We present a case of late-onset KD in a 55-year-old male with a novel pathogenic GALC variant, aiming to highlight the features and investigation findings that should prompt consideration of the diagnosis. In addition, we describe the course of illness, emphasizing the importance of multi-disciplinary team (MDT) input in patient care and the role of novel blood-based and imaging biomarkers.

Source: American Journal of Medical Genetics Part A

DOI: 10.1002/ajmg.a.64031