Genetic basis of Congenital methemoglobinemia in Poodles and Pomeranians - is caused by a mutation in the CYB5R3 gene, which encodes NADH-cytochrome b5 reductase (b5R).This enzyme is essential for the reduction of methemoglobin (an oxidized form of hemoglobin unable to carry oxygen) back to hemoglobin.A specific missense mutation (c.580A>C, p.Ile194Leu) in CYB5R3 has been identified in affected Pomeranian families. The disorder is inherited as an autosomal recessive trait, requiring two copies of the mutated gene for clinical signs to appear.
Pathophysiology - Deficiency of NADH-cytochrome b5 reductase leads to the accumulation of methemoglobin in red blood cells. Methemoglobin cannot bind oxygen, impairing oxygen delivery to tissues. Clinical signs include cyanosis (bluish discoloration) of mucous membranes, tongue, and skin. Affected dogs often show mild to moderate exercise intolerance. Despite discoloration, many dogs have a relatively normal lifespan and do not require constant treatment.
Clinical Signs - Persistent bluish or purple coloration of gums, tongue, and skin (cyanosis). Exercise intolerance. Brown colored blood due to increased methemoglobin. Rarely, severe episodes may require veterinary care but most live relatively normal lives.
Diagnosis - Physical exam and blood color.Methemoglobin quantification in blood. Reduced b5R enzyme activity tests. Genetic testing confirming the CYB5R3 mutation.
Why This Matters to Breeders and Vets - Breeders: Genetic testing is important to prevent breeding two carriers, which can produce affected puppies. Vets: Recognizing the condition prevents misdiagnosis or unnecessary treatment; management focuses on supportive care as needed. Genetic counseling helps maintain healthy breeding practices.