Urinary liver-type fatty acid-binding protein in two dogs with acquired Fanconi syndrome: A case report.

Background: Fanconi syndrome (FS) is defined as multiple defects of the proximal tubules and is diagnosed by clinical symptoms. However, in dogs with FS, the damage in the proximal tubules that is responsible for the clinical symptoms has not been evaluated. Among FS cases, tubular damage in acquired FS is reversible following the elimination of a causative factor. Liver-type fatty acid-binding protein (L-FABP) is a biomarker of tubular damage in various animals including dogs. Urinary L-FABP measurement may be useful for the diagnosis and follow-up evaluation in canine FS. Case Description: At the first visit, two Toy Poodles that had no remarkable findings on physical examination presented with glycosuria without hyperglycemia, hypokalemia, hyperchloremia, increased levels of plasma alkaline phosphatase, and metabolic acidosis. Considering all the factors involved, the dogs were clinically diagnosed with acquired FS. The owner reported that they routinely fed the dog with chicken jerky, a recently considered cause of acquired FS. Following the withdrawal of the jerky, abnormalities including glycosuria improved in both dogs. Moreover, urinary L-FABP levels, which were high at diagnosis, presented a decreasing trend during the follow-up. However, in one dog, the elevated urinary L-FABP level did not return to normal. Conclusion: Although the clinical symptoms of acquired FS in dogs could be improved by the elimination of a causative factor, the severity of tubular damage described by urinary L-FABP may not be necessarily linked to the degree of functional deterioration. Therefore, the evaluation of proximal tubular damage by L-FABP may be of clinical value during the follow-up of acquired FS in canines.

[Acquired transient Fanconi syndrome after feeding jerky treats in dogs - A case series]. / Erworbenes transientes Fanconi-Syndrom nach Fütterung von Trockenfleisch als Leckerchen beim Hund.

Between April 2018 and August 2019, 6 dogs with laboratory diagnostic evidence of Fanconi syndrome were presented to the Tierklinik Hofheim. The presumptive diagnosis was confirmed via urine amino acid analysis in all dogs. In 5 of the 6 dogs an alimentary origin was suspected, in 3 dogs the course of the disease could be followed. Supportive therapeutic measures and elimination of jerky treats from the dogs' diet improved the clinical symptoms in all dogs with known follow-up. This is the first case series of dogs with alimentary acquired Fanconi syndrome in Germany. The frequency of occurrence of the disease in that short period of time in only one small animal clinic suggests a significantly higher incidence than currently assumed.

Transient Fanconi Syndrome After Treatment with Firocoxib, Cefadroxil, Tramadol, and Famotidine in a Maltese.

Fanconi syndrome is a renal proximal tubulopathy characterized by excessive urinary loss of glucose, amino acids, several electrolytes, and bicarbonate. Here, we report the case of transient Fanconi syndrome in a dog following administration of firocoxib, cefadroxil, tramadol, and famotidine. A 10 mo old Maltese was presented with lethargy, anorexia, vomiting, and weight loss. Transient Fanconi syndrome without azotemia was associated with firocoxib, cefadroxil, tramadol, and famotidine treatment. The dog received supportive care including IV fluids, gastroprotectants, and oral nutritional supplements. Two months after initial diagnosis and treatment, the dog showed complete resolution of glucosuria and aminoaciduria. The unique features of Fanconi syndrome in this case emphasize the potential renal tubular toxicity of this widely used multiple-drug combination.

[Fanconi-Bickel-Syndrom: a novel genetic disease in Original Braunvieh]. / Fanconi-Bickel-Syndrom: eine bislang unerkannte Erbkrankheit beim Braunvieh.

INTRODUCTION: This case report describes a new genetic disease of the Braunvieh breed in Switzerland. The bovine disorder also occurs in German Fleckvieh, and corresponds to human Fanconi-Bickel syndrome which is an inherited glycogen storage disease caused by mutations of the SLC2A2 gene encoding the glucose transporter GLUT2. This case report describes a single affected Original Braunvieh calf genotyped as homozygous for the FH2-associated SLC2A2 frame shift mutation. The clinical examination showed stunted growth, polyuria and polydipsia, as well as poor claw horn and coat quality. Necropsy revealed a pale cortex of the kidneys and a unilateral renal hypoplasia. Histology showed tubulonephrosis of the proximal tubules with protein- and glucose-rich contents. Glycogen accumulation was not evident in any organ. This finding is different from the reported lesions in two previously described GLUT2-deficient Fleckvieh heifers. In the presented case, growth retardation mainly seems to be associated with renal dysfunction. A direct gene test is available to eliminate the mutant allele from the population.

Fanconi Syndrome in Irish Wolfhound Siblings.

Three juvenile male Irish wolfhound littermates presented with marked polyuria and polydipsia. The four female siblings were apparently unaffected. Diagnostic testing revealed glucosuria with normoglycemia, generalized aminoaciduria, hypokalemia and metabolic acidosis consistent with Fanconi syndrome. Renal ultrasonographic and histologic findings are presented. Cases were managed with a supplementation regimen based on a treatment protocol for Fanconi syndrome in basenjis. These dogs did not have angular limb deformities as documented previously in juvenile canine siblings with Fanconi syndrome. Fanconi syndrome has not been previously described in Irish wolfhound siblings.

Acquired Fanconi syndrome in two dogs following long-term consumption of pet jerky treats in Japan: case report.

Renal Fanconi syndrome has recently been associated with the ingestion of pet jerky treats from China in mostly small breed dogs in North America, Australia and Europe. We report here about two dogs with Fanconi syndrome following pet jerky treats exposure in Japan. A mixed-breed dog and a French bulldog showed weight loss, polyuria and polydipsia. For years, the owners had been feeding large quantities of pet jerky treats containing chicken prepared in China. Diagnostics revealed glycosuria without hyperglycemia, severe aminoaciduria, and in one case also ketonuria, hypokalemia and metabolic acidosis. A diagnosis of Fanconi syndrome associated with long-term consumption of Chinese pet jerky treats was made. Both dogs recovered fully following withdrawal of the pet jerky treats and supportive care. Fanconi syndrome of dogs in association with the consumption of pet jerky treats of Chinese origin can cause a broad proximal tubular defect with glycosuria and generalized amino aciduria, and should be also considered in Asia. Jerky treats associated Fanconi syndrome can be completely reversible following withdrawal of the treats and supportive care to correct the metabolic abnormalities.

Aminoaciduria Caused by Fanconi Syndrome in a Heifer.

A case study of renal tubular dysfunction consistent with idiopathic Fanconi syndrome is reported in an 18-month-old Holstein heifer. The clinical, biochemical, and histopathological features are described. The heifer had clinical signs of growth retardation, wasting, and persistent diarrhea. Biochemical blood analysis identified hypokalemia, hyponatremia, and hypochloremia. Urinalysis identified glycosuria, proteinuria, and acidic pH. Histological examination of the kidney disclosed mild tubular necrosis with proteinaceous casts in the lumina of renal tubules. We performed LC-HRMS on urine to confirm Fanconi syndrome. Using this technique, we identified severe generalized aminoaciduria suggestive of idiopathic renal Fanconi syndrome in this heifer.

Clinical and biochemical signs in Fleckvieh cattle with genetically confirmed Fanconi-Bickel syndrome (cattle homozygous for Fleckvieh haplotype 2).

Fanconi-Bickel Syndrome (FBS) is an autosomal recessive disorder of the carbohydrate metabolism, which has been reported in human and some animals (OMIA 000366-9913). In Fleckvieh cattle it is caused by mutations in SLC2A2, a gene encoding for glucose transporter protein 2 (GLUT2), which is primarily expressed in liver, kidney, pancreas and intestines. The causal mutation resides in a previously reported Fleckvieh Haplotype 2 (FH-2). FH-2 homozygous individuals are rare, but due to widespread use of heterozygous bulls in artificial insemination, heterozygous animals are likely to be present in a larger number in the cattle population. Two clinical cases of Fleckvieh cattle with a syndrome resembling the phenotypic appearance of FBS are presented in the present study describing the association between the clinical manifestations of FBS and the postulated frameshift mutation in bovine SLC2A2. Clinical examination showed poor growth, retarded development, polyuria, and polydipsia. Laboratory analyses showed an increased plasma glucose but normal insulin concentration and increased renal glucose excretion. Histopathological examination of kidney and liver samples revealed massively increased liver glycogen storage and nephrosis. Sires of both cases were tested positive for being heterozygous carriers for the same frameshift mutation in SLC2A2 as was originally reported in Fleckvieh cattle. DNA of both cases described was analyzed and Sanger sequencing confirmed homozygosity for the frameshift mutation in SLC2A2.

Acquired Fanconi syndrome in four cats treated with chlorambucil.

CASE SERIES SUMMARY: Fanconi syndrome (FS) is well described in humans and dogs, but has not been reported in cats. This case series describes four cats with acquired FS. On the basis of clinical signs and intestinal biopsies, all cats were initially diagnosed with alimentary lymphoma or inflammatory bowel disease. Treatment with chlorambucil and corticosteroids was started at standard doses, based on published protocols. Within 2-26 months of the start of treatment, glucosuria, despite normoglycemia, was identified incidentally on routine biochemical screening; FS was diagnosed with urine metabolic assays, confirming aminoaciduria and glucosuria in all four cases. Neither polyuria nor polydipsia were noted in any case, and only 1/4 cats had any clinical signs at the time of diagnosis. Partial or complete resolution of FS was seen in 3/4 cases within 3 months of discontinuing chlorambucil therapy. RELEVANCE AND NOVEL INFORMATION: This is the first case series to document acquired FS in the cat, and the first to suggest a possible association between chlorambucil and acquired FS. Cats treated with chlorambucil should be monitored for the development of glucosuria, and discontinuation of chlorambucil should be considered if FS is identified. Further study into the association between chlorambucil and acquired FS in cats is warranted.

Acquired Fanconi syndrome in a dog exposed to jerky treats in Japan.

A 6-year-old spayed female Jack Russell Terrier presented with a 1-month history of lethargy, anorexia, vomiting and weight loss. The dog was fed beef and chicken jerky treats daily in addition to a commercial diet. Laboratory tests revealed azotemia, hypokalemia, hyperchloremia, metabolic acidosis and glucosuria with normoglycemia. Urine amino acid analysis showed significant amino acid loss into the urine. Thus, Fanconi syndrome was diagnosed, and based on the case history and extensive diagnostic testing, excessive consumption of jerky treats was strongly suspected as the cause. Glucosuria resolved 7 days after the withdrawal of jerky treats and fluid therapy. Aminoaciduria was substantially, but not completely, improved 3 months after diagnosis. Mild azotemia remained, suggesting chronic renal disease. To the best of our knowledge, this is the first reported case of Fanconi syndrome following the consumption of jerky treats in Japan.

Homozygous haplotype deficiency reveals deleterious mutations compromising reproductive and rearing success in cattle.

BACKGROUND: Cattle breeding populations are susceptible to the propagation of recessive diseases. Individual sires generate tens of thousands of progeny via artificial insemination. The frequency of deleterious alleles carried by such sires may increase considerably within few generations. Deleterious alleles manifest themselves often by missing homozygosity resulting from embryonic/fetal, perinatal or juvenile lethality of homozygotes. RESULTS: A scan for homozygous haplotype deficiency in 25,544 Fleckvieh cattle uncovered four haplotypes affecting reproductive and rearing success. Exploiting whole-genome resequencing data from 263 animals facilitated to pinpoint putatively causal mutations in two of these haplotypes. A mutation causing an evolutionarily unlikely substitution in SUGT1 was perfectly associated with a haplotype compromising insemination success. The mutation was not found in homozygous state in 10,363 animals (P=1.79×10(-5)) and is thus likely to cause lethality of homozygous embryos. A frameshift mutation in SLC2A2 encoding glucose transporter 2 (GLUT2) compromises calf survival. The mutation leads to premature termination of translation and activates cryptic splice sites resulting in multiple exon variants also with premature translation termination. The affected calves exhibit stunted growth, resembling the phenotypic appearance of Fanconi-Bickel syndrome in humans (OMIM 227810), which is also caused by mutations in SLC2A2. CONCLUSIONS: Exploiting comprehensive genotype and sequence data enabled us to reveal two deleterious alleles in SLC2A2 and SUGT1 that compromise pre- and postnatal survival in homozygous state. Our results provide the basis for genome-assisted approaches to avoiding inadvertent carrier matings and to improving reproductive and rearing success in Fleckvieh cattle.

Transient renal Fanconi syndrome in a Chihuahua exposed to Chinese chicken jerky treats.

Transient Fanconi syndrome without azotemia was diagnosed in a dog and was associated with ingestion of Chinese chicken jerky treats. Fanconi syndrome is a proximal renal tubular defect and a diagnosis was made based upon severe glucosuria with normoglycemia, and severe generalized aminoaciduria. The clinical signs of polyuria and polydipsia as well as the massive urinary metabolic abnormalities resolved after jerky treat withdrawal. While frequently seen in North America and Australia, this is the first report of jerky treat induced Fanconi syndrome in continental Europe. Clinicians should be aware of this potential intoxication and be vigilant for a history of jerky treat consumption in a dog with glucosuria.

Transient Fanconi syndrome with severe polyuria and polydipsia in a 4-year old Shih Tzu fed chicken jerky treats.

Acquired Fanconi syndrome is characterized by inappropriate urinary loss of amino acids, bicarbonate, electrolytes, and water. It has recently been described in dogs fed chicken jerky treats from China, a new differential diagnosis to the classical inciting infectious diseases (e.g. leptospirosis, pyelonephritis) and toxins. A dog fed exclusively chicken jerky treats purchased in Switzerland was presented to our clinic with severe polyuria, polydipsia and profound electrolyte and acid base disturbances. Other inciting causes of Fanconi syndrome were ruled out. The requirement of a very intensive supportive treatment in this dog stands in contrast to treatment of chronic forms of Fanconi syndrome as described in the Basenji. This intensive therapy and the associated monitoring can be a real challenge and a limiting factor for the prognosis of acquired Fanconi syndrome. Veterinarians should be aware of the risk of excessive feeding of chicken jerky treats.

Transient Fanconi syndrome in Quarter horses.

Two Quarter horses with weight loss had glucosuria, euglycemia, and a mild metabolic acidosis suggesting a proximal renal tubular defect. Further testing revealed transient generalized aminoaciduria, lactic aciduria, and glucosuria, indicating Fanconi syndrome. Both horses recovered with supportive therapy. This is the first report of acquired Fanconi syndrome in horses.

Syndrome de Fanconi transitoire chez des chevaux Quarter horse. Deux chevaux Quarter horse ayant subi une perte de poids étaient atteints de glucosurie, d'euglycémie et d'une acidose métabolique légère suggérant un défaut tubulaire rénal proximal. De nouveaux tests ont révélé une amino-acidurie, une acidurie lactique et une euglycémie généralisée transitoire, indicatif du syndrome de Fanconi. Les deux chevaux se sont rétablis avec une thérapie de soutien. Il s'agit du premier rapport du syndrome de Fanconi acquis chez les chevaux.(Traduit par Isabelle Vallières).

Determination of six illegal antibiotics in chicken jerky dog treats.

In 2007 chicken jerky dog treats were implicated in causing illnesses and death in dogs in several countries. Affected dogs were diagnosed with acquired Fanconi syndrome, which is characterized by kidney malfunction. Known causes of this condition include a chemical assault by various contaminants including certain drugs. For this reason investigations into possible causes of the illnesses included antibiotics that may be used in animal husbandry. Targeted analyte screens of individual imported chicken jerky dog treats using LC-MS/MS detected six illegal antibiotics in imported products of several brands. Trimethoprim, tilmicosin, enrofloxacin, sulfaclozine, and sulfamethoxazole are not allowed in chicken at any level and were found as high as 2800 ng/g (ppb). Sulfaquinoxaline was found in chicken jerky treats as high as 800 ng/g, which is well above the U.S. FDA tolerance of 100 ng/g. Although there is no evidence these contaminants were responsible for the dog illnesses, their misuse could contribute to antibiotic-resistant strains of bacteria.

Fanconi syndrome in four non-basenji dogs exposed to chicken jerky treats.

Four small-breed dogs were diagnosed with acquired Fanconi syndrome. All dogs ate varying amounts of chicken jerky treats. All dogs were examined for similar clinical signs that included, but were not limited to, lethargy, vomiting, anorexia, diarrhea, and altered thirst and urination. The quantity of chicken jerky consumed could not be determined; however, based on the histories obtained, the chicken jerky treats were a significant part of the diet and were consumed daily by all dogs. Extensive diagnostic testing eliminated other causes of the observed clinical signs, such as urinary tract infection and rickettsial disease. Glucosuria in the face of euglycemia or hypoglycemia, aminoaciduria, and metabolic acidosis confirmed the diagnosis of Fanconi syndrome. All dogs received supportive care, including IV fluids, antibiotics, gastroprotectants, and oral nutritional supplements. Three dogs exhibited complete resolution of glucosuria, proteinuria, and the associated azotemia; however, one dog remained azotemic, resulting in a diagnosis of chronic kidney disease.