JPC SYSTEMIC PATHOLOGY

URINARY SYSTEM

December 2023

U-M21 (NP)

 

Signalment (JPC # 1945143): Rat

 

HISTORY: Tissue from a rat fed a leguminous plant of the genus Swainsona.

 

MICROSCOPIC DESCRIPTION: 

SLIDE A: Kidney: Diffusely within the cortex proximal tubular epithelial cells are swollen and contain abundant clear cytoplasmic vacuoles that are 2-50 µm in diameter, often peripheralize the nucleus, and obscure or occlude tubular lumina. Tubules occasionally contain intraluminal eosinophilic amorphous material (protein cast). Within the medulla, epithelial cells of tubules and collecting ducts are mildly to moderately vacuolated. Occasional cells in glomerular tufts are distended by cytoplasmic vacuolation. Multifocally, there are low numbers of lymphocytes and plasma cells in the interstitium.

 

MORPHOLOGIC DIAGNOSIS: Kidney, tubular epithelium: Vacuolation, cytoplasmic, diffuse, severe, rat, rodent.

 

CAUSE: Swainsonine toxicity (toxic inhibition of alpha-mannosidase)

 

CONDITION: Acquired alpha-mannosidosis

 

Signalment (JPC # 1640-4): Calf

 

HISTORY: Tissue from a neonatal Salers calf.

 

HISTOPATHOLOGICAL DESCRIPTION: 

SLIDE B: Kidney: Diffusely, tubular epithelial cells are swollen, severely vacuolated, and often obscure or occlude tubule lumina. Vacuoles are 2-40 um in diameter and peripheralize nuclei. Multifocally there are occasional lymphocytes and plasma cells in the interstitium.

 

Spinal cord: Multifocally, neurons have numerous intracytoplasmic vacuoles that are 1-10 µm in diameter and often obscure or displace Nissl substance.

 

MORPHOLOGIC DIAGNOSIS (U-M21b): Kidney, tubular epithelium: Vacuolation, cytoplasmic, diffuse, severe, Salers, bovine.

 

Spinal cord, neurons: Vacuolation, cytoplasmic, multifocal, moderate.

 

CONDITION: Autosomal recessive hereditary beta-mannosidosis

 

GENERAL DISCUSSION: 

• Note – the neurologic manifestations of acquired (N-T01) or inherited (N-M14) alpha- and beta-mannosidosis are covered in the neurologic systemics 
• Glycoproteinoses, a type of lysosomal storage disease, are a group of diseases with defective degradation of the carbohydrate component of N-linked glycoproteins; includes alpha-mannosidosis, beta-mannosidosis, and alpha-L-fucosidosis
• Mannosidosis is genetic or acquired and results in accumulation of mannose-containing oligosaccharides 

 

PATHOGENESIS:

• Congenital (autosomal recessive) alpha-mannosidosis: Occurs primarily in cattle (Angus, Murray Gray, Galloway) and cats (Persian, domestic short or longhair) due to deficient alpha-mannosidase and affects virtually all cells except hepatocytes; synthesis of a defective enzyme protein --> deficient lysosomal alpha-mannosidase activity --> lysosomal buildup of mannose/N-acetylglucosamine oligosaccharides
• Induced/acquired alpha-mannosidosis (“locoism”): Due to ingestion of broomweed (Sida carpinifolia), Astragalus, Oxytropis, or Swainsona plants which have a fungal endophyte (Undifilum oxytropis) that produces swainsonine (an indolizidine alkaloid), which inhibits lysosomal and Golgi alpha-mannosidase, thus inducing acquired alpha-mannosidosis that mimics inherited storage disease 
• Congenital beta-mannosidosis: Occurs primarily in Salers cattle, Nubian goats, and German shepherd dogs due to deficient glucohydrolase β-mannosidase, leading to accumulation of beta-mannose containing oligosaccharides in nervous, renal, thyroid, and lymphoid tissues
  1. MANBA gene mutation identified in German shepherd dogs

 

TYPICAL CLINICAL FINDINGS:

• No abnormalities in renal parameters or function 
• Retarded growth, neurologic signs (e.g. ataxia, behavioral changes)

 

TYPICAL GROSS FINDINGS:

• Kidneys: Renomegaly 
• Brain: Dilated lateral ventricles
• Musculoskeletal: Carpal contractures (goats with beta-mannosidosis)
• Reproductive: Hydrallantois, adventitial placentation

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Marked intracytoplasmic vacuoles in various tissues, to include the proximal convoluted tubules (as well as neurons, pancreas, thyroid epithelium, reticuloendothelial cells)
• Hypomyelination in the brain

 

ULTRASTRUCTURAL FINDINGS:  

 

ADDITIONAL DIAGNOSTIC TESTS:

 

Comparative List of lysosomal storage Diseases

 

Disease	Storage Product	Deficient enzyme	Species	Breed
GM1 gangliosidosis	GM1 ganglioside	b-galactosidase	Bovine Canine     Feline Ovine	Holstein-Friesian Beagle, English Springer spaniel, Portuguese water dog Siamese, DSH Suffolk, Coopworth-Romney
GM2 gangliosidosis	GM2 ganglioside	b-hexosaminidase	Canine     Feline Porcine	German shorthair pointer, Japanese  Spaniel DSH, Korat Yorkshire
Globoid-cell Leukodystrophy (krabbe’s-like disease)	Galactosylceramide (galactocerebroside) Galactosylsphingosine (psychosine)	Galactoslceramidase (galactocerebroside b-galactosidase)	Canine         Feline Ovine	West Highland terrier, Cairn terrier, Miniature poodle, blue tick hound, beagle, Pomeranian DSH Polled Dorset
a-mannosidosis	Mannose-containing oligosaccharide	a-mannosidase	Bovine   Feline	Angus, Murray Gray, Galloway Persian, DSH
b-mannosidosis	Mannose-containing oligosaccharide	b-mannosidase	Caprine Bovine	Nubian Salers
Mucopolysaccharidosis	Different glycosaminoglycans	Several different enzyme deficiencies	Canine     Feline Caprine	Plott hound (type I, Hurler’s disease) miniature pinscher (type VI, Maroteaux-Lamy disease) DSH(type I, Type VII sly disease) Nubian (type III, sanfilippo’s disease)
Ceroid-lipofuscinosis	Subunit c of mitochondrial ATPase	Prelysosomal defect?	Canine   Ovine Bovine	English setter, border collie, Tibetan terrier South Hampshire Devon
	Sphingolipid Activating proteins A & D	Palmitoyl protein thioesterase	Canine Ovine	Miniature schnauzer   Swedish Landrace
Niemann-Pick type c disease	Primarily ganglioside in neurons	Unknown	Ovine Bovine Feline Canine	Ramouillet Beefmaster Siamese, DSH Boxer

 

References:

1. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd; 2015:257-258, 286, 288-289.
2. Cianciolo RE, Mohr FC. Urinary System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:429. 
3. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:502. 
4. Jolly RD, Dittmer KW, Garrick DJ., et al. β-Mannosidosis in German Shepherd Dogs. Vet Pathol 2019;56(5):743-748.
5. Miller AD, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:940, 943-945.
6. Njaa BL. The Ear. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1372.
7. Reis MO, Cruz RA, Oliveira LGS, et al. Hydrallantois in cows naturally poisoned by Sida carpinifolia in Brazil. J Vet Diagn Invest. 2019; 31(4):581-584.

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