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Storage disease
Synonym(s): Metabolic storage disease; degenerative storage disease, ceroid lipofuscinosis (ceroidosis, fucosidosis, gangliosidosis (GM1, GM2, globoid cell leucodystrophy (Krabbe's disease, sphingomyelinosis (Niemann-Pick disease, sphingomyelin lipidosis, glycogen storage disease (glycogenosis type Ia, II, III, VII, Gaucher's disease (glucocerebrosidosis, mucopolysaccharidosis (MPS I, II, IIIa, VI, VII.
Introduction
- Group of genetic diseases associated with failure of metabolic pathway → accumulation of substances within lysosomal system → impaired cellular function.
- Signs: multifocal neurological signs.
- Cause: specific enzyme deficiency due to genetic defect, may occur as breed-specific inherited disease. Usually autosomal recessive mode of inheritance.
- Signs: chronic, progressive neurological signs - ataxia, behavioral change, blindness, seizures and tetraplegia.
- Diagnosis: lysosomal enzyme analysis or molecular genetic testing.
- Treatment: none.
- Prognosis: poor.
Presenting signs
- Most commonly associated with onset of clinical signs in immature animals.
- In other cases early clinical signs may be very subtle or absent, resulting in adult animals that present with clinical signs of disease.
- Vary according to underlying defect and reflect the abundance of the enzyme substrate within a particular tissue of the body, since substrate accumulation leads, directly or indirectly, to cellular dysfunction.
- All diseases have progressive clinical signs and are ultimately fatal.
- Progressive blindness.
- Possible neurological signs: behavior changes, seizures, cerebellar dysfunction and tetraparesis.
Age predisposition
- 2 months to 2 years old.
- >2 years old (ceroid lipofuscinosis mucopolysaccharidoses can occur in older individuals Neuronal ceroid lipofuscinosis).
Breed/Species predisposition
Ceroid lipofuscinosis
- Australian Cattle dog Australian Cattle Dog.
- Border Collie Border Collie.
- Chihuahua - long coat Chihuahua - Long Coat.
- Chihuahua - smooth coat Chihuahua - Smooth Coat.
- Dachshund Dachshund.
- English Setter English Setter.
- Saluki Saluki.
- Cocker Spaniel English Cocker Spaniel.
Fucosidosis
- English Springer Spaniel English Springer Spaniel.
Gaucher's disease
- Australian Silky Terriers Silky Terrier.
Gangliosidosis GM1, GM2
- Beagle Beagle.
- German Short-haired Pointer German Shorthaired Pointer.
- Portuguese Water dog Portuguese Water Dog.
- English Springer Spaniel English Springer Spaniel.
- Alaskan Husky.
Globoid cell leukodystrophy (Krabbe's disease)
- Basset Hound Basset Hound Globoid cell leukodystrophy.
- Beagle Beagle.
- Cairn Terrier Cairn Terrier.
- Dalmatian Dalmatian.
- Pomeranian Pomeranian.
- Miniature Poodle Poodle: miniature.
- Standard Poodle Poodle: Standard.
- Toy Poodle Poodle: Toy.
- West Highland White Terrier West Highland White Terrier.
- Coonhounds.
Glycoproteinosis
- Beagles Beagle.
- Basset Hound Basset Hound.
- Poodles.
Glucocerebrosidosis
- Sydney Silky dog.
Glycogenosis
- Toy breeds.
- Lapland dog.
- German Shepherd German Shepherd Dog.
- Akitas Akita.
- English Springer Spaniel.
- Maltese terrier Maltese.
Sphingomyelinosis (Niemann-Pick disease)
- Miniature Poodle Poodle: miniature Niemann Pick disease.
- Standard Poodle Poodle: Standard.
- Toy Poodle Poodle: Toy.
- Boxer Boxer.
Mucopolysaccharidosis
- Plott hound.
- Minature Pinscher.
- Labrador Retriever Retriever: Labrador.
- Dachshunds Dachshund.
- Schipperke Schipperke.
Cost considerations
- Moderate to high costs can be incurred in diagnostic work-up.
Special risks
- General anesthesia - must monitor oxygen supply carefully because hypoxia due to seizure activity and airway compromise → cytotoxic brain edema → possibly increased intracranial pressure.
Pathogenesis
Etiology
- Sphingomyelinosis - deficiency of sphingomyelinase.
- GM1 gangliosidosis - deficiency of beta-galactosidase.
- GM2 gangliosidosis - deficiency of hexosaminidase.
- Glucocerebrosidase - deficiency of beta-glucosidase.
- Ceroid lipofuscinosis - deficiency of phenylene-diamine-mediated peroxidases.
- Globoid cell leukodystrophy - deficiency of beta-galactocerebrosidase.
- Mucopolysaccharidosis - deficiency of alpha1-iduronidase.
- Fucosidosis - deficiency of alpha-fucosidase.
- Glycogenosis - deficiency of alpha-glucosidase.
Specific
- Most of these breed-specific diseases are thought to be hereditary (usually as an autosomal recessive inheritance).
Pathophysiology
- Defect in genes coding for specific lysosomal acid hydrolases (involved in lysosomal catabolic pathway) → accumulation and storage of substrate(s) of various cells throughout the nervous system (neurons, glial cells, macrophages or Schwann cells) as well as in cells in other organs → distension of lysosome → neuronal cell distension → impaired function, eg meganeurites may have aberrant synaptic formation/distribution → neurologic dysfunction.
Timecourse
- Slowly progressive over months.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- Recent references from PubMed and VetMedResource.
- Skelly B J & Franklin R J M (2002) Recognition and diagnosis of lysosomal storage diseases in the cat and dog. JVIM 16 (2) 133-144 PubMed.
- Jolly R D, Ehrlich P C, Franklin R J M et al (2001) Histological diagnosis of mucopolysaccharidosis IIIA in a wire-haired dachshund. Vet Rec 148 (18), 564-567 PubMed.
- Cozzi F et al (1998) MRI and electrophysiological abnormalities in a case of canine globoid cell leucodystrophy. JSAP 39 (8), 401-405 PubMed.
- Fischer A et al (1998) Sulfaminidase deficiency in a family of dachshunds - a canine model of mucopolysaccharidosis IIIa (Sanfilipo A). Pediatric Res 44 (1), 74-82 PubMed.
- Holmes N G et al (1998) A PCR-based diagnostic test for fucosidosis in English Springer Spaniels. Vet J 155 (2), 113-114 PubMed.
- Müller G et al (1998) Biochemical findings in a breeding colony of Alaskan Huskies suffering from GMI-gangliosidosis. J Inher Metab Dis 21 (4), 430-431 PubMed.
- Brix A E et al (1995) Glycogen storage disease Type Ia in two littermate Maltese puppies. Vet Pathol 32 (5), 460-465 PubMed.
- Jolly R D, Palmer D N & Studdert V P et al (1994) Canine ceroid lipofuscinoses - a review and classification. JSAP 35 (6), 299-306 VetMedResource.
- Kuwamura M et al (1993) Type C Niemann-Pick disease in a boxer dog. Acta Neuropathol 85 (3), 345-348 PubMed.
- Alroy J et al (1992) Canine GM-gangliosidosis - a clinical, morphologic, histochemical and biochemical comparison of two different models. Am J Pathol 140 (3), 675-689 PubMed.
- Sisk D B et al (1990) Clinical and pathological features of ceroid lipofuscinosis in two Australian cattle dogs. JAVMA 197 (3), 361-364 PubMed.
- Taylor R M, Martin I C A, Farrow B R H (1989) Reproduction abnormalities in canine fucosidosis. J Comp Pathol 100 (4), 369-380 VetMedResource.
- Barker C G, Herrtage M E, Sharahan F & Winchester (1988) Fucosidosis in English Springer spaniels - results of a trial screening programme. JSAP 29 (10), 623-630 VetMedResource.
- Vicini D S et al (1988) Peripheral nerve biopsy for diagnosis of globoid cell leucodystrophy in a dog. JAVMA 192 (8), 1087-1090 PubMed.
Other sources of information
- Merck Veterinary Manual (1998 )8, pp 907-911.
- Oliver J E (1997) Handbook of Veterinary Neurology 3. pp 279, 343-345.
- Ettinger S J (1995) Textbook of Veterinary Internal Medicine 4. pp 528, 618, 659, 708, 719.
- DeLahunta A (1983) Veterinary Neuroanatomy and Clinical Neurology 2. pp 272, 296.