Metabolic Storage Disorders and Inborn Errors of Metabolism

Storage diseases and inborn errors of metabolism are classified as either genetic or acquired. These diseases are characterized by the accumulation or storage of specific lysosomal enzyme substrates or byproducts within cells because of partial or complete deficiency of those enzymes. Although lysosomal storage diseases are often widespread throughout the body, the majority of clinical signs are due to the effects on the CNS.

Genetic storage diseases are named according to the specific metabolic byproduct that accumulates in the lysosomes. Animals are typically normal at birth, then manifest clinical signs within the first weeks to months of life. These diseases are progressive and usually fatal, because specific treatments do not exist. In small animals, the gangliosidoses (GM₁ and GM₂) are seen in Siamese, Korat, and domestic cats, and in Beagle crosses, German Shorthaired Pointers, and Japanese Spaniels. Sphingomyelinosis is seen in German Shepherds and Poodles and in Siamese and domestic shorthaired cats. Glucocerebrosidosis is seen in Australian Silky Terriers and Dalmatians. Ceroid lipofuscinosis is seen in English Setters, Cocker Spaniels, Dachshunds, Chihuahuas, Salukis, Border Collies, and domestic cats. Mannosidosis is seen in Persian and domestic cats. Glycogenosis is seen in Silky Terriers and in domestic shorthaired and Norwegian forest cats. Globoid cell leukodystrophy (Krabbe disease) is seen in Cairn Terriers, West Highland White Terriers, Beagles, Bluetick Hounds, Poodles, and domestic shorthaired cats. Mucopolysaccharidosis type I is seen in Siamese, Korat, and domestic shorthaired cats; type IV is seen in Siamese cats. In dogs, mucopolysaccharidosis is seen in Miniature Pinschers, Plott Hounds, and mixed-breed dogs and is associated with lameness. Diseases associated with decreased RBC survival and anemia include pyruvate kinase deficiency in Basenjis, Beagles, and West Highland White and Cairn Terriers; phosphofructokinase deficiency in English Springer and American Cocker Spaniels; and porphyria in Siamese and domestic shorthaired cats.

In large animals, α-mannosidosis occurs in Angus, Murray Grey, Simmental, Galloway, and Holstein cattle. β-Mannosidosis is seen in Saler cattle and Nubian and Nubian-cross goats. Generalized glycogenosis (GM₁) is seen in Holstein cattle and Suffolk sheep. Generalized glycogenosis (GM₂) is seen in Shorthorn and Brahman cattle, and in pigs. Globoid cell leukodystrophy is seen in polled Dorset sheep. Other identified diseases that are manifest by neurologic signs and appear to be inherited include neuronal lipodystrophy in Angus and Beefmaster cattle, shaker calf syndrome of horned Hereford cattle, maple syrup urine disease of Hereford and polled Shorthorn cattle, and hereditary neuraxial edema of polled and horned Hereford and Hereford-Friesian cross cattle. There have been no reports of lysosomal storage diseases in horses; however, inherited diseases manifest by neurologic signs include inherited myoclonus of Peruvian Paso foals and congenital encephalomyelopathy in Quarter horses.

Other inherited diseases that involve basic errors of metabolism in various tissues include goiter of sheep and goats, inherited parakeratosis (edema disease) of cattle, osteogenesis imperfecta of sheep and cattle, and possibly cardiomyopathy of cattle, the hypotrichoses, baldy calves, photosensitization of sheep (see Photosensitization), dermatosis vegetans and porcine stress syndrome (see Malignant Hyperthermia) of pigs, dermatosparaxia and Ehlers-Danlos syndrome of cattle, hemochromatosis of cattle (see Hemochromatosis), and Marfan syndrome in cattle. Many other inherited defects, especially those based on abnormal growth of collagen, cartilage, and bone, also are likely to have basic errors of metabolism of structural tissues. Many disorders of metabolism have been described involving dysfunctions of the immune system.

Acquired storage diseases are caused by ingestion of plants that contain inhibitors of specific lysosomal catabolic enzymes. Chronic ingestion of locoweed plants (Astragalus or Oxytropis spp) results in an acquired neurologic storage disease. Several toxic components, including locoine, swainsonine n-oxide, and indolizidine alkaloids, interfere with α-mannosidase activity. Horses are most susceptible to intoxication; however, cattle, sheep, and goats can also be affected. (Also see Range Plants of Temperate North America.)