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A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review

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Abstract

Krabbe disease (KD) is a rare autosomal recessive lipid storage leukodystrophy. It is caused by deficient enzyme activity resulting from mutations of the β-galactocerebrosidase (GALC) gene. KD is distinguished into subtypes based on the age of onset; these are early infantile, late infantile, juvenile, and adult-onset. We report a case of a 47-year-old Caucasian man with a 2-year history of muscle atrophy and weakness in both hands associated with pyramidal signs and mild spasticity in the lower limbs. An extensive work-up led this motor neuron disease-like disorder to be diagnosed as adult-onset KD. The patient was found to be compound heterozygous for two GALC mutations (p.G286D and p.Y490N). These two rare missense mutations have previously been reported with other heterozygous mutations. However, their co-occurrence in a KD patient is novel. From the perspective of this case, we review the current literature on compound heterozygous mutations in adult-onset KD and their phenotypic variability.

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Acknowledgements

We thank the patient and his parents who agreed to participate in this report.

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Authors and Affiliations

  1. ALS Clinical Research Center, P Giaccone University Hospital and Department of Biomedicine, Neuroscience and advanced Diagnostic (BIND), University of Palermo, via Gaetano La Loggia n° 1, 90129, Palermo, Italy

    Salvatore Iacono, Vincenzo La Bella & Rossella Spataro

  2. Research & Innovation (R&I Genetics) srl, C/so Stati Uniti 4, int F, 35127, Padova, Italy

    Elda Del Giudice & Alberta Leon

Authors
  1. Salvatore Iacono
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  2. Elda Del Giudice
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  3. Alberta Leon
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  4. Vincenzo La Bella
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  5. Rossella Spataro
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Contributions

SI and RS diagnosed and followed up with the patient. EDG and AL performed the genetic analyses. SI and VLB drafted the manuscript. RS and VLB designed the report and made the final revision. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Vincenzo La Bella.

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Iacono, S., Del Giudice, E., Leon, A. et al. A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review. Neurogenetics 23, 157–165 (2022). https://doi.org/10.1007/s10048-021-00682-1

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  • DOI: https://doi.org/10.1007/s10048-021-00682-1

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