Categories: Homeostasis / metabolism phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608782 (trait) , 605993 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0012120: pyruvate dehydrogenase phosphatase deficiency

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2007

Cross-species summary: PDH deficiency.

Species-specific description: 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

Mapping: CFA (29)

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

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).

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.

Breeds: Clumber Spaniel (Dog) (VBO_0200366), Sussex Spaniel (Dog) (VBO_0201309).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: