A SINE-like insertion in intron 13 of the ATP7A gene is associated with a mild form of Menkes-like disease in a Cavalier King Charles Spaniel.

ATP7A variants causing Menkes-like disease should be considered in dogs with Fanconi syndrome and unexplained neurological signs.

A 7-month-old intact male Cavalier King Charles Spaniel presented with persistent glucosuria despite normoglycemia, failure to thrive, chronic diarrhea, and cerebellar ataxia. Fanconi syndrome was diagnosed; however, the concurrent neurological signs were not fully attributable to this condition, prompting suspicion of an underlying hereditary disorder. Whole genome sequencing revealed a private hemizygous SINE-like insertion within intron 13 of the ATP7A gene, located near the exon 14 splice site. In humans, pathogenic variants in ATP7A cause Menkes disease, an X-linked disorder of copper metabolism characterized by progressive neurodegeneration, connective tissue abnormalities, and a broad clinical spectrum. This represents the first reported case of a clinically affected dog with an ATP7A variant consistent with Menkes-like disease. The phenotype in this dog appeared milder than classical human Menkes disease, potentially due to the intronic location of the variant and partial preservation of gene function. This case broadens the spectrum of known copper metabolism disorders in dogs beyond copper-associated hepatitis and highlights the diagnostic value of whole genome sequencing in cases of unexplained hereditary disease. The authors advocate for expanded genetic screening and phenotypic characterization of copper metabolism variants in dogs, which may also provide a naturally occurring animal model for human metabolic diseases. Clinicians should consider copper metabolism disorders in dogs presenting with atypical combinations of renal tubular dysfunction and neurological signs.

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