Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D.

BACKGROUND: A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. METHODS: Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis. RESULTS: Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, ß, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents. CONCLUSIONS: This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

Hyperinsulinaemic, hypoglycaemic syndrome due to acquired nesidioblastosis in a cat.

Case summary A 6-year-old, neutered female British Shorthair cat presented with acute-onset weakness and mental dullness. Initially the cat was mildly hyperglycaemic (9.9 mmol/l; reference interval [RI] 3.3-6.7 mmol/l). Over the following 12 h the cat developed central blindness, tremors, intermittent seizures and opisthotonus. Repeat blood sampling revealed a marked hypoglycaemia (0.8 mmol/l). Insulin level (performed on a serum sample collected while the cat was hypoglycaemic) was inappropriately elevated (1575 mIU/l; RI 10-80 mIU/l). An abdominal ultrasound was unremarkable. An exploratory laparotomy revealed a firm and erythematous left limb of the pancreas. Following surgical resection of the left limb of the pancreas, the cat returned to a euglycaemic state after a brief rebound hyperglycaemia. Histopathology revealed pancreatic fibrosis with marked multifocal micronodular hyperplasia of exocrine and endocrine cells. Synaptophysin immunohistochemistry confirmed nodular ß-cell hyperplasia. Relevance and novel information Nesidioblastosis describes a syndrome of acquired hyperinsulinaemia and associated hypoglycaemia secondary to focal or diffuse (non-neoplastic) ß-cell hyperplasia within the pancreas. Acquired nesidioblastosis has been reported in humans, where ß-cell dysregulation is thought to occur in response to pancreatic injury. This is the first reported case of clinically significant hypoglycaemia due to acquired nesidioblastosis in an adult domestic cat. While this condition is rare, nesidioblastosis is being increasingly recognised in humans and it is an important differential diagnosis to consider when investigating hypoglycaemia as it cannot be distinguished from insulinoma without histopathological evaluation. While recurrence has been occasionally reported in humans, the prognosis is considered good.