Genetic basis - Caused by a mutation in the G6PC gene (glucose-6-phosphatase), specifically a G to C substitution at nucleotide 363 (c.363 G>C, p.M121I) in exon 3 in Maltese dogs. The G6PC enzyme is crucial for glucose production from glycogen; the mutation leads to reduced enzyme activity (about 15 times less than normal). The disease is inherited in an autosomal recessive pattern — two mutated copies are required to develop the disease; carriers have one copy and are asymptomatic.
Pathophysiology - Deficiency or lack of functional G6PC enzyme impairs the liver's ability to break down glycogen into glucose, leading to glycogen accumulation in liver, kidney, muscle, and heart cells. This results in hypoglycemia, lactic acidosis, hepatomegaly (enlarged liver), muscle weakness, and growth retardation. Accumulation of glycogen causes cellular dysfunction and eventual organ failure.
Complications - Affected puppies often die in utero, are stillborn, or die within a few months post-birth. Symptoms include severe hypoglycemia, failure to thrive, lethargy, enlarged liver, difficulty breathing, and muscle weakness. Soft tissue mineralization can occur, including in kidneys and lungs. No effective cure exists; supportive care is the only option.
Why This Matters to Breeders and Vets - For breeders, preventing production of puppies with this fatal metabolic disorder preserves breed health and reduces loss. Veterinarians use genetic testing and clinical signs for early diagnosis and counseling owners on prognosis and care. The autosomal recessive inheritance pattern informs responsible breeding practices.