How is Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency inherited in dogs?

Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency follows a Autosomal recessive inheritance pattern, associated with the PDP1 gene.

Is there a genetic test for Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency?

Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency is associated with the PDP1 gene. Where a validated DNA test for the causal variant is available, it can identify dogs carrying the variant before breeding. Per-breed variant frequency figures are published in the Sniff Atlas (242,664 dogs screened).

What is the human equivalent of Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency?

OMIA links Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency to its human counterpart in OMIM (OMIM 608782), the bridge to the deeper human-medicine literature for the same underlying biology.

Canine Mendelian disease record

Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency

Q: How well studied is Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency in dogs?

OMIA curates 6 peer-reviewed references for Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency. The full, linked citation list is on this page.

Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency. Autosomal recessive. Observed in 0 of 266 breeds tested in the Sniff Atlas, with measured variant frequencies drawn from 242,664 dogs (Donner 2023). Whether a dog carrying this variant is at risk depends on the disease’s inheritance pattern; outcome also depends on penetrance, modifiers, and environment. The frequencies below describe variant prevalence, not confirmed disease incidence.

OMIA identifier: OMIA:001406-9615
Inheritance: Autosomal recessive
Linked gene: PDP1
Human counterpart: In humans, this gene is PDP1. OMIM 605993 In people, PDP1 rarely tolerates loss-of-function variation (gnomAD v4.1 constraint, LOEUF 0.53), a sign it does important, dosage-sensitive work. In people, variants in the PDP1 gene have conflicting classifications in ClinVar, and none is expert-reviewed. The evidence is unsettled, not that variants here are benign.
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human pyruvate dehydrogenase phosphatase deficiency

Dogs with this condition carry a change in PDP1. In people, changes in the same gene cause pyruvate dehydrogenase phosphatase deficiency. This canine condition is studied as a natural model of pyruvate dehydrogenase phosphatase deficiency in people; it is not the same as a human pyruvate dehydrogenase phosphatase deficiency diagnosis. Studying dogs can move medicine forward for everyone; the canine disease remains the subject.

In people, the disease is described as: Pyruvate dehydrogenase phosphatase deficiency is a very rare subtype of pyruvate dehydrogenase deficiency (PDHD) characterized by lactic acidemia in the neonatal period.

In humans it is also called: PDHPD, PDH phosphatase deficiency.

MONDO:0012120 OMIM 608782

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 2026-08-27.

Summary

Deficiency in pyruvate dehydrogenase phosphatase 1 in Clumber and Sussex Spaniels is characterized by exercise intolerance, lactic acidosis, and collapse after exercise. The causative mutation is the same in these breeds. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Clinical features

Affected dogs show exercise intolerance, lactic acidosis, and post-exercise collapse. Management includes exercise restriction and a high-fat diet with thiamine and carnitine supplementation (Cameron et al., 2007).

Molecular genetics

Cameron et al. (2007): c.754C>T; p.Q252* in Clumber spaniels and Sussex spaniels

Pathology

PDP1 is a key component of the pyruvate dehydrogenase complex (PDHC) that controls the rate of tricarboxylic acid entry into the citric acid cycle. During exercise, large quantities of lactate and pyruvate are generated through the anaerobic pathway. PDP1 deficiency causes severe reduction in pyruvate entry into the citric acid cycle, leading to insufficient generation of ATP and lactate and pyruvate acidosis when muscle is exercised (Cameron et al., 2007).

Prevalence

Of 100 Clumber Spaniels tested, 20 were carriers and 1 was homozygous for the mutation. There is thought to be a high frequency of heterozygotes amongst Clumber Spaniels, but fewer affected dogs alive than expected. This suggests that affected dogs may be at risk for prenatal or neonatal mortality (Cameron et al., 2007).

Control

Since the Clumber and Sussex Spaniel gene pools are small in the USA, gradual elimination of the mutation can be achieved by testing all dogs prior to breeding, and to breeding carriers only to noncarriers. Breeding of affected dogs should be avoided.

Genetic testing

There is a test available to identify carrier and affected dogs.

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 608782 Gene · OMIM 605993

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001406-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

OMIA curates the disease definition, the clinical description and the reference list. The cross-species disease identity is Monarch's. Sniff renders these and adds the breed-level frequencies, the plain-language summary, and a stated reason wherever a number is missing.

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as pyruvate dehydrogenase phosphatase deficiency (MONDO:0012120).

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.

Identification of a canine model of pyruvate dehydrogenase phosphatase 1 deficiency. · Mol Genet Metab · 2007 · PMID 17095275
Pyruvate dehydrogenase deficiency in a Sussex spaniel. · J Small Anim Pract · 2004 · PMID 15049576
Pyruvate dehydrogenase deficiency in Clumber and Sussex spaniels in the United States and Belgium · J. Vet. Intern. Med. · 2000
Mitochondrial myopathy in the Sussex spaniel. · Vet Rec · 1980 · PMID 7361423
Collapsing Clumber spaniels. · Vet Rec · 1979 · PMID 552740
Collapsing Clumber Spaniels · Veterinary Record · 1979 · PMID 516334

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.

Your breed

See what Pyruvate Dehydrogenase Phosphatase 1 (PDP1) Deficiency looks like in your dog's breed.

Variant frequency by breed

Observed only in small-sample breeds

Maximum variant frequency per breed across variants in the Donner 2023 cohort, with Wilson 95% confidence intervals. 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.

Scope of this record

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 variant frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

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:001406-9615.
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.

Gene page: PDP1, cited identity, disease associations, and the human-gene bridge.
Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:001406-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated August 27, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001406-9615 · Donner et al. 2023 · gnomAD v4.1 (Karczewski 2020) · ClinVar (Landrum 2018)