Histological diagnosis of mucopolysaccharidosis IIIA in a wire‐haired dachshund

Abstract

A four-year-old wire-haired dachshund developed progressive neurological signs of ataxia, intention tremor and finally dysuria. Two years later, histopathology showed that neurons throughout the brain and spinal cord were distended with lipopigment which was also present in macrophages. Ultrastructurally, the pigment in the neurons occurred predominantly as electron-dense membranous whorls and stacks. There were a few vacuolated macrophages in the meninges. Hepatocytes were highly vacuolated and electron microscopy suggested that they were empty membrane-bound vesicles. The disease was diagnosed as mucopolysaccharidosis IIIA because of its similarity to other biochemically confirmed cases in the same breed and in a New Zealand huntaway dog. Additional lesions included calcium oxalate uroliths, severe secondary calcification of tissues including the brain and storage deposits in some neurons, and lesions which may have been associated with high levels of the substrate, heparan sulphate.

Pathological and Biochemical Studies of Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome Type B) in Juvenile Emus (Dromaius novaehollandiae)

“…34,40,41 These staining properties are consistent with the storage of GM2 and GM3 gangliosides, as demonstrated in MPS type IIIB in humans and other animals. 15,19,35 The detection of lipid vacuoles within the cytoplasm of hepatocytes (hepatic lipidosis) is consistent with previous reports, both in MPS type III 25,43 and other types of mucopolysaccharidosis, such as MPS types I and VI. 7,43 This fatty change is considered secondary to the metabolic derangement and cell injury caused by the accumulation of GAGs.…”

“…37,56 In humans, the natural course of the neurological disease is similar in all subtypes: initially aggressiveness and hyperactivity, later progressing to mental retardation and, ultimately, CNS degeneration, 47 although an attenuated course with late presentation may also occur. 38 In addition to humans, naturally occurring MPS type IIIA has been described in Dachshund 16,25 and New Zealand Huntaway dogs, 24,56 type IIIB in Schipperke dogs [13][14][15] and cattle, 30 and type IIID in goats. 27,28,46 Here, we describe the clinical, pathological, biochemical, and molecular features of emus affected with MPS type IIIB.…”

Magnetic resonance findings in a domestic short‐hair cat with presumptive mucopolysaccharidosis

“…The vacuolar changes found in the lymphocytes, neutrophils and hepatocytes have been described in dogs and cats (Crawley and others 1998, Jolly and others 2001, Macri and others 2002, Dombrowski and others 2004, Jolly and others 2007). The enzymatic assay was suggestive of Gangliosidosis but the reference ranges used for this test were the same used for human paediatric patients which might explain the discrepancy between the enzymatic assay and the genetic test.…”

“…MPS are lysosomal storage diseases in human beings and domestic animals generally inherited by an autosomal recessive trait (Skelly and Franklin 2002, Hordeaux and others 2011). MPS have been described in cats (Coates and Kline 1995, Crawley and others 1998, Schultheiss and others 2000, Macri and others 2002, Crawley and others 2003, Hordeaux and others 2011), dogs (Coates and Kline 1995, Haskins and Giger 1997, Ray and others 1998, Wilkerson and others 1998, Jolly and others 2001, Ellinwood and others 2003, Dombrowski and others 2004, Jolly and others 2007, Hordeaux and others 2011), rats (Yoshida and others 1993a, b), mice (Birkenmeier and others 1989, Clarke and others 1997, Tomatsu and others 2005), goats (Thompson and others 1992) and emus (Aronovich and others 2001) (Tables 1 and 2). Affected animals are normal at birth but they then have progressive growth abnormalities and generally exhibit neurologic abnormalities, skeletal abnormalities, or both (Crawley and others 1998, Jolly and others 2001, Crawley and others 2003).…”

Pathology of Mucopolysaccharidosis IIIA in Huntaway Dogs

“…Most patients die in their late teens or early twenties, by which time there is moderate cortical atrophy of the brain. MPSIIIA has also been described in Wirehaired Dachshund dogs, 8,12 Huntaway dogs, 11,28 and mice. 6,16 In the 2 canine breeds, the mutations are different.…”