Sulfamidase deficiency in a family of dachshunds: A canine model of mucopolysaccharidosis IIIA (Sanfilippo A)

Andrea Fischer, K. Paige Carmichael, John F. Munnell, Perseus Jhabvala, Jerry N. Thompson, Reuben Matalon, Peter F. Jezyk, Ping Wang, Urs Giger

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59 Scopus citations


Mucopolysaccharidosis IIIA (MPS IIIA or Sanfilippo A, McKusick 25290) was diagnosed in two adult wire-haired Dachshund littermates. Clinical and pathologic features paralleled the human disorder; both dogs exhibited progressive neurologic disease without apparent somatic involvement. Pelvic limb ataxia was observed when the dogs were 3 y old and progressed gradually within 1-2 y to severe generalized spinocerebellar ataxia. Mentation remained normal throughout the course of the disease. A mucopolysaccharide storage disorder was indicated in both dogs by positive toluidine blue spot tests of urine. The diagnosis of MPS IIIA was confirmed by documentation of urinary excretion and tissue accumulation of heparan sulfate and decreased sulfamidase activity in fibroblasts and hepatic tissue. Mild cerebral cortical atrophy and dilation of the lateral ventricles were grossly evident in both dogs. Light microscopically, fibroblasts, hepatocytes, and renal tubular epithelial cells were vacuolated. Within the nervous system, cerebellar Purkinje cells, neurons of brainstem nuclei, ventral and dorsal horns, and dorsal ganglia were distended with brightly autofluorescent, periodic acid-Schiff-positive, sudanophilic material. Ultrastructurally, visceral storage presented as membrane-bound vacuoles with finely granular, variably electron-lucent contents. Neuronal storage appeared as membranous concentric whorls, lamellated parallel membrane stacks, or electron-dense lipid-like globules. This represents the first reported animal disease homolog of the human Sanfilippo A syndrome.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalPediatric Research
Issue number1
StatePublished - Jul 1998

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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