Genetic basis - Fanconi syndrome can be inherited or acquired. The inherited form is often seen in certain dog breeds (notably Basenjis), and is typically the result of an autosomal recessive mutation. In Basenjis, a homozygous deletion in the FAN1 gene has been identified as a major genetic cause. The mutation leads to dysfunction in the DNA repair pathway, specifically affecting the renal proximal tubule cells. Other genetic disorders associated with Fanconi syndrome include cystinosis (CTNS gene), Wilson disease, hereditary fructose intolerance, Lowe syndrome, mitochondrial cytopathies, and tyrosinemia. Inheritance patterns can vary, but autosomal recessive inheritance is most common
Pathophysiology - Fanconi syndrome affects the kidneys’ proximal tubules, which normally reabsorb water, electrolytes, and critical nutrients. In affected animals, these tubules fail to reabsorb substances like sodium, potassium, glucose, phosphate, bicarbonate, and amino acids, allowing them to spill into the urine. This loss results in clinical signs including metabolic acidosis, glucosuria (with normal blood sugar), aminoaciduria, and phosphaturia. Over time, these derangements can cause dehydration, rickets, poor growth, and eventually kidney failure
Complications - If Fanconi syndrome is undiagnosed or untreated, complications can progress to renal (kidney) failure, which is life-threatening. Other issues include persistent metabolic imbalances, growth retardation, skeletal deformities (due to phosphate loss), and secondary complications from chronic dehydration. Dogs affected by inherited Fanconi syndrome usually show clinical signs between ages 4 and 7 years, but earlier onset is possible. When kidney failure develops, the prognosis is poor.
Why This Matters to Breeders and Vets - Fanconi syndrome is a chronic and potentially fatal disease that can impact breed health, reputation, and animal welfare. For breeders, ensuring genetic screening prevents transmission and decreases disease prevalence, protecting both their lines and the breed as a whole. For vets, awareness enables early diagnosis and intervention, which can improve quality of life and delay progression to kidney failure. Managing breeding practices and veterinary care together is vital for reducing suffering and improving health outcomes in affected breeds