What question did this study set out to answer?

To clinically and genetically characterize a creatine deficiency disorder myopathy in a family of dogs.

January 23, 2026Open Access

Myopathy due to a creatine deficiency disorder in a family of mixed breed dogs with a glycine amidinotransferase gene mutation

Key Result

Creatine and L-carnitine supplementation improved clinical signs in two dogs with creatine deficiency myopathy caused by a GATM mutation after just three days of treatment.

Key Points

To clinically and genetically characterize a creatine deficiency disorder myopathy in a family of dogs.
Evaluated three sibling dogs for clinical, imaging, electrodiagnostic, and histopathologic data.
Conducted whole genome sequencing and bioinformatics to identify a genetic variant.
Confirmed the variant through Sanger sequencing in related dogs.
Affected dogs showed clinical signs such as megaesophagus and muscle atrophy.
CT scans revealed diffuse muscle lesions, and electromyography indicated abnormal muscle activity.
Histopathology demonstrated type 2 fiber atrophy and excessive lipid droplets in type 1 fibers.

Structured PICO

Does creatine and L-carnitine supplementation improve clinical signs in dogs with creatine deficiency disorder due to a GATM variant?

Population

3 siblings from the same litter of mixed breed dogs (2 clinically affected with megaesophagus and generalized muscle atrophy, 1 clinically normal)

Intervention

Creatine (800-1500 mg/kg/day) and L-carnitine (80-150 mg/kg) supplementation

Outcome

Clinical improvement and response to treatment

Creatine and L-carnitine supplementation provides rapid clinical improvement in dogs with a novel creatine deficiency disorder myopathy caused by a GATM missense variant.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Background Myopathies caused by genetic abnormalities are increasingly recognized in veterinary medicine. Hypothesis/Objectives Clinically and genetically characterize a novel creatine deficiency disorder (CDD) myopathy in a family of mixed breed dogs. Animals Three siblings from the same litter were evaluated and genetically tested, including 2 dogs that were clinically affected and one dog clinically normal. All dogs were client owned. Methods Case series describing clinical, imaging, electrodiagnostic, histopathologic investigations, and response to treatment. Whole genome sequencing and bioinformatics were performed to identify a causative variant followed by Sanger sequencing to confirm the suspected variant in related dogs. Results Clinical signs included megaesophagus with generalized muscle atrophy in both affected dogs. One dog showed exercise intolerance. Computed tomography (CT) scan revealed bilateral and symmetrical diffuse hypoattenuating muscle lesions. Electromyography was characterized by nonspecific abnormal spontaneous activity in electrodiagnostically affected muscles. Type 2 fiber atrophy and excessive intramyofiber lipid droplets in type 1 muscle fibers were the predominant findings in histopathology. Both affected dogs were homozygous for a unique GATM p. R414C (NP₀01274013. 1) missense variant, while the unaffected sibling did not have this variant. All clinical signs improved after 3 days of creatine (800-1500 mg/kg/day) and L-carnitine (80-150 mg/kg) supplementation and remained stable at the time of writing 4 months after diagnosis. Conclusions and clinical importance This is a report of CDD in dogs characterized by a glycine amidinotransferase (GATM) variant, which showed a good short-term outcome with supplementation with creatine and L-carnitine.