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Canine Mendelian disease record

Globoid Cell Leukodystrophy (Discovered in Terriers)

Globoid Cell Leukodystrophy (Discovered in Terriers). Autosomal recessive. Observed in 3 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:000578-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human Krabbe disease

Dogs with this condition carry a change in GALC. In people, changes in the same gene cause Krabbe disease. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: A lysosomal disorder that affects the white matter of the central and peripheral nervous systems. It includes infantile, late-infantile/juvenile and adult forms.

In humans it is also called: GLD, diffuse globoid body sclerosis, galactocerebrosidase deficiency, galactosylceramidase deficiency, galactosylceramide lipidosis.

MONDO:0009499 OMIM 245200

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

Also known as globoid cell leukodystrophy (GLD), galactosylceramide lipidosis, galactocerebrosidase deficiency, GALC deficiency, globoid cell leukoencephalopathy, galactosylceramide beta-galactosidase deficiency. A lysosomal storage disease in which there is a buildup (storage) of myelin, due to the lack of the enzyme galactosylceramidase (galactocerebrosidase), whose task is to break down myelin into its constituent molecules. Characterised by weakness progressing to paralysis.

Clinical features

Clinical signs are usually apparent in affected dogs by 4-6 weeks of age (Corado et al., 2020). Affected dogs initially present with tremors and pelvic limb weakness which then progresses to pelvic limb ataxia as well as thoracic limb dysmetria, followed by tetraparesis and then eventually hind limb paralysis (Corado et al., 2020). Other clinical signs may include a wide-based stance, hypermetria, generalised incoordination and muscle atrophy (Bradbury et al., 2018). [IT thanks DVM student Sharna Allison, who provided the basis of this contribution in April 2022]

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Victoria et al. (1996) identified the cause of this disorder, in both West Highland White terriers and Cairn terriers, as a base substitution (A to C transversion) at position 473 of the cDNA for galactocerebriosidase (GALC), resulting in an amino acid substitution (tyrosine to serine) at position 158 in the peptide. They have developed a PCR genotyping test which is being used within both breeds, to identify carriers. In an Irish Setter family, McGraw and Carmichael (2006) identified a 78 bp insertion in the same gene as the causative mutation. Hammack et al. (2023) identified a "novel missense variant in GALC (NC_006590.4:g.58893972G>A)" as the putatively causative variant for globoid cell leukodystrophy in a family of mixed-breed dogs with 4 affected puppies. "Among the related dogs (n = 33), 3 dogs were homozygous and 7 heterozygous. The variant allele was not detected in screening 278 dogs from 5 breeds. The novel variant is either unique to this family or has an extremely low allele frequency in the general population."

Pathology

This disease results in extensive characteristic white matter demyelination, globoid cell infiltration and low leukocyte galactosylceramidase activity (Fletcher et al., 2010). Demyelination usually begins in the spinal cord, peripheral nerves and hindbrain before progressing to the cerebellum (Fletcher et al., 2010). Histopathological changes in GLD-affected dogs include reactive astrocytosis and microglial activation (Fletcher et al., 2010). Psychosine, a GALC substrate, is believed to be responsible for cell death in GLD (Corado et al., 2020). [IT thanks DVM student Sharna Allison, who provided the basis of this contribution in April 2022]

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 245200 Gene · OMIM 606890

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000578-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as Krabbe disease (MONDO:0009499).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (doi:10.25910/2AMR-PV70, CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 39.

  5. Efficacy and safety of a Krabbe disease gene therapy. · Hum Gene Ther · 2022 · PMID 35333110

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Globoid Cell Leukodystrophy (Discovered in Terriers) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Globoid Cell Leukodystrophy (Discovered in Terriers) looks like in your dog's breed.
Carrier frequency by breed

Top 3 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%3%5%
Cairn Terrier0.82% · n 183
West Highland White Terrier<0.1% · n 658
American Staffordshire Terrier<0.1% · n 42,793
n = 43,634 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Globoid Cell Leukodystrophy (Discovered in Terriers) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Cairn Terrier 0.82% 183
West Highland White Terrier <0.1% 658
American Staffordshire Terrier <0.1% 42,793

263 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:000578-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:000578-9615 · Donner et al. 2023