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“Atypical” Krabbe disease in two siblings harboring biallelic GALC mutations including a deep intronic variant

European Journal of Human Genetics volume 30, pages 984–988 (2022)Cite this article

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Abstract

Krabbe disease (KD) is a rare lysosomal storage disorder caused by biallelic pathogenic variants in GALC. Most patients manifest the severe classic early-infantile form, while a small percentage of cases have later-onset types. We present two siblings with atypical clinical and neuroimaging phenotypes, compared to the classification of KD, who were found to carry biallelic loss-of-function GALC variants, including a recurrent 30 kb deletion and a previously unreported deep intronic variant that was identified by mRNA sequencing. This family represents a unique description in the KD literature and contributes to expanding the clinical and molecular spectra of this rare disorder.

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Fig. 1: Serial T2-weighted brain MRI images of patient 1.
Fig. 2: Molecular analyses.
Fig. 3: T2-weighted brain MRI images of patient 2.

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Data availability

Additional data are available from the corresponding author on reasonable request.

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Acknowledgements

The parents are fully acknowledged for their perseverance and patience in both diagnostic and therapeutic phases of their nice sons. FN and EB are members of the European Reference Network for Rare Neurological Diseases – Project ID No 739510.

Funding

The authors report no targeted funding.

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Authors and Affiliations

  1. Genetics and Rare Diseases Research Division, Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Francesco Nicita, Fabrizia Stregapede, Chiara Aiello, Francesca Cumbo, Fiorella Piemonte, Jessica D’Amico, Enrico Bertini & Lorena Travaglini

  2. Division of Metabolism, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Federica Deodato

  3. Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Simone Pizzi & Marco Tartaglia

  4. Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

    Simone Martinelli

  5. Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Daria Pagliara

  6. Neurophysiology Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Stefano Pro

  7. Neuroradiology Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Daniela Longo

  8. Translational Cytogenomics Research Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy

    Silvia Genovese

  9. Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Maria L. Escolar

Authors
  1. Francesco Nicita
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  2. Fabrizia Stregapede
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  10. Jessica D’Amico
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  14. Marco Tartaglia
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  15. Maria L. Escolar
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  17. Lorena Travaglini
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Contributions

The corresponding author has had full access to the data in the study and final responsibility for the decision to submit for publication. All contributing authors have met the following criteria: conceived and/or designed the work that led to the submission, acquired data, and/or played an important role in interpreting the results; drafted or revised the manuscript; approved the final version; agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding authors

Correspondence to Francesco Nicita or Lorena Travaglini.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki. Parents signed consent forms for genetic analyses, participation to this study, and for data publication.

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Nicita, F., Stregapede, F., Deodato, F. et al. “Atypical” Krabbe disease in two siblings harboring biallelic GALC mutations including a deep intronic variant. Eur J Hum Genet 30, 984–988 (2022). https://doi.org/10.1038/s41431-022-01111-z

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