Fanconi Syndrome Basenji Type (FS)
Fanconi Syndrome Basenji type is a genetic disorder caused by proximal renal tubular dysfunction. Fanconi syndrome was named after swiss doctor Guido Fanconci, who was first to describe the disorder in 1936. Canine Fanconi syndrome was first reported in 1976 in Basenji dog breed. FS can be divided into hereditary and idiopathic (the cause is not known). Idiopathic FS has been identified in the Norwegian Elkhound, Labrador Retriever, Shetland Sheepdog and Miniature Schnauzer. Forms of FS that are acquired as result of toxic effects of certain drugs or heavy metal poisoning are also common.
Characteristics and Symptoms
In Fanconi syndrome proximal renal tubular epithelial cells are insufficient, which leads to the urinary leakage, or insufficient apsorption of essential metabolites such as phosphate, uric acid, glucose, amino acids and low molecular weight proteins.
First symptoms of Fanconi syndrome in Basenjis are exhibited around 3 to 7 year of age. Clinical signs are excessive drinking (polydipsia), excessive urination (polyuria), glucose in the urine (glucosuria), because the kidneys are unable to conserve water. Other symptoms are also weight loss and poor hair coat. If the disorder is left untreated for longer time, due to the loss of nutrients and electrolites in the urine, muscle wasting, acidosis, and poor condition will develop. In case of rapid progress of disorder into kidney failure, signs as poor appetite, extreme loss of weight, lethargy, vomiting and pale gums due to anemia will appear. Due to glucose in the urine, affected dogs are prone to urinary tract infection.
When untreated at all, affected dog will eventually die from the disorder. If the disorder is treated on time, individual affected dogs can do well with their condition. Since affected dogs have urinary leakage, to determine wether the dog is affected, urine glucose test strips are used. Those test strips show presence or absence of glucose in the urine. Veterinarian examination include urine specific gravity, glucosuria with normogylcemia, phosphaturia and aminoaciduria.
Fanconi Syndrome Basenji type (FS) is caused by a mutation in FAN1 gene (Fanconi anemia-associated nuclease 1), which is a part of the myotubularin gene family of tyrosine phosphatases. Gene name has been proposed because FAN1 protein interacts with Fanconi anemia (FA) pathway proteins. FA and FS in Basenjis are caused by mutation in same gene, but these two disorders are distant. This muation causes FAN1 inactivation, which results in hyper-sensitization of the proximal tubule cells to low concentrations of heavy-metals in FS affected Basenjis. Since affected dogs are differently exposed to environmental toxins, this exaplins the wide range of ange of onset for Fanconi syndrome in Basenjis.
The disorder is inherited as an autosomal recessive trait. Healthy parents of an affected dog are obligate heterozygotes, and therefore carry one mutant allele. Heterozygotes have no symptoms. At conception, each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Farias, F. H. G. (2011.): MOLECULAR GENETIC STUDIES OF CANINE INHERITED DISEASES. A dissertation presented to the Faculty of the Graduate School University of Missouri.