Succinic semialdehyde dehydrogenase deficiency in Saluki

The enzyme succinic semialdehyde dehydrogenase is an important part of the metabolism of the neurotransmitter GABA (gamma-aminobutyric acid). It converts succinic semialdehyde to succinic acid during the Krebs cycle. In the affected dogs, neurological abnormalities, including seizures and behavioural changes can be observed. They show atrophy of the cerebral cortex with vacuolization, increased levels of gamma-hydroxybutyric acid in blood serum, cerebrospinal fluid and brain, and increased levels of succinic semialdehyde in urine, cerebrospinal fluid, and brain.

Succinic semialdehyde dehydrogenase deficiency is caused by the c.866G>A missense mutation in the ALDH5A1 gene.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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Reference:

Vernau, K.M., Struys, E., Letko, A., Woolard, K.D., Aguilar, M., Brown, E.A., Cissell, D.D., Dickinson, P.J., Shelton, G.D., Broome, M.R., Gibson, K.M., Pearl, P.L., König, F., Van Winkle, T.J., O'Brien, D., Roos, B., Matiasek, K., Jagannathan, V., Drögemüller, C., Mansour, T.A., Brown, C.T., Bannasch, D.L. : A missense variant in ALDH5A1 associated with canine succinic semialdehyde dehydrogenase deficiency (SSADHD) in the Saluki dog. Genes (Basel) 11:1033, 2020. Pubmed reference: 32887425