Page 1885 - Cote clinical veterinary advisor dogs and cats 4th

Storage Diseases 945.e3

○ Mentation changes (behavioral changes, ○ Dandy-Walker syndrome ○ Measures lysosomal enzyme activity for
a panel of known lysosomal enzymes
○ Miscellaneous malformations
aggression, loss of learned behavior) • Infectious ○ Performed using whole blood leukocytes,
VetBooks.ir ○ Gait abnormalities (ataxia, paresis) ○ Fungal (Cryptococcus neoformans, Coc- kidney or liver biopsy samples, or cultured Diseases and Disorders
○ Menace deficits, central blindness
○ Proprioceptive deficits
skin fibroblasts
cidioides immitis, Histoplasma capsulatum,
○ Intention tremors
○ Exercise intolerance Blastomyces dermatitidis), viral (canine ○ Available for some enzymes (i.e., some
storage diseases) and the level of activity
distemper virus, feline immunodeficiency
• Hepatomegaly (gangliosidosis, glycogenosis virus [FIV], feline leukemia virus [FeLV], of an affected animal can be compared
types I and III, mannosidosis, muco- feline infectious peritonitis [FIP]), pro- with an age-matched control
polysaccharidoses types I and VII, and tozoal (Neospora caninum, Toxoplasma ○ Because these diseases are commonly
sphingomyelinosis) and splenomegaly (muco- gondii, Hepatozoon americanum), and autosomal recessive, an affected animal
polysaccharidosis type I, sphingomyelinosis) verminous, rickettsial, and bacterial would have significantly decreased enzyme
have been noted as a result of accumulation meningoencephalitis activity, and a heterozygous carrier would
of storage products in the cells of these • Inflammatory have 50% of the enzyme activity of a
organs. ○ Necrotizing meningoencephalitis of small- homozygous animal.
• Can exhibit skeletal or connective tissue breed dogs • Molecular genetic testing for affected gene
abnormalities (mannosidosis, mucopolysac- ○ Granulomatous meningoencephalomyelitis (DNA testing)
charidoses types I and VI, mucolipidosis (GME) ○ The specific genetic mutation responsible
type II) ○ Eosinophilic meningoencephalitis for a disease can vary among different
• Retinal degeneration with ceroid lipofusci- • Metabolic species and breeds, and molecular testing is
nosis and in cats with mucolipidosis II ○ Organic acidurias (e.g., L-2-hydroxyglutaric very specific concerning breed and species
• Dwarfism with gangliosidosis in English aciduria in the Staffordshire bull terrier, for any given disease.
springer spaniels malonic aciduria in the Maltese) • Histopathologic evaluation
• Peripheral nerve involvement associated with ○ Mitochondrial encephalopathies (e.g., ○ Peripheral nerve, muscle, liver, or lymph
fucosidosis, globoid cell leukodystrophy, pyruvate dehydrogenase deficiency in node biopsy can be diagnostic in some
glycogenoses, sphingomyelinosis Sussex spaniels) cases.
○ Hepatic, renal, hypoglycemic, and ○ Brain biopsy guided by CT or MRI
Etiology and Pathophysiology electrolyte-associated encephalopathies ○ Postmortem/necropsy
• Normally, substances undergo sequential • Neoplastic: primary or metastatic ■ Requires use of special staining
metabolic degradation by specific lysosomal • Nutritional: thiamine deficiency techniques to characterize the specific
enzymes. Interruptions in these specific • Toxic: lead storage product
pathways can occur if one enzyme (or • Vascular: global ischemia, thromboembolic
more) is deficient or dysfunctional, leading disease TREATMENT
to accumulation of the substance before that
enzymatic step. Initial Database Treatment Overview
• Accumulated byproduct(s) lead to cellular • CBC, serum biochemical profile, urinalysis • Goal is to reduce the accumulation of cellular
dysfunction, presumably by cell swelling, ○ May reveal leukocytes containing vacuoles storage products.
toxic effects of accumulated material(s), or or storage product • Mostly limited to supportive care and
both. ○ Some disorders show evidence of multiple maintenance of quality of life for as long
affected organs. as possible
DIAGNOSIS ○ Performed to rule out other metabolic • Therapeutic options being explored include
disorders gene therapy or transferring normal copies of
Diagnostic Overview • Serologic titers: performed to rule out infec- the dysfunctional gene to the patient’s cells
These uncommon disorders are suspected in tious diseases using a viral vector. After the functional copy
young patients with relentlessly progressive of the gene becomes incorporated into the
neurologic deficits with or without associated Advanced or Confirmatory Testing cell, it begins to produce the deficit enzyme.
general physical abnormalities. Confirmatory • Supportive diagnostic tests This has been shown effective in treatment
clinical tests exist for some disorders; definitive ○ Cerebrospinal fluid (CSF) analysis of certain canine and feline storage diseases
diagnosis is obtained from histologic analysis ■ Typically normal (dogs: mucopolysaccharidosis [MPS] types
of tissue, typically when unthrifty animals die ■ Protein level can be elevated, but nucle- I, IIIB, and VII; cats: alpha-mannosidosis,
or are euthanized. Genetic testing confirmatory ated cell count should remain normal. GM 1 and GM 2 gangliosidosis, MPS I and
for some. ○ CT or MRI VI)
■ Brain atrophy with secondary
Differential Diagnosis ventriculomegaly Acute and Chronic Treatment
Any slowly progressive multifocal or diffuse ■ Diffuse changes in tissue intensity (due Supportive care
encephalopathy, cerebellar dysfunction, or neu- to accumulation of storage products)
romuscular dysfunction should be considered • Confirmatory diagnostic tests (available only Recommended Monitoring
as a differential diagnosis. for certain storage disorders) can identify • Progressive neurologic impairment is expected.
• Degenerative specific storage products, deficient enzyme • Monitoring for quality of life
○ Leukodystrophy/spongy degeneration activity, and/or presence of the defective gene
○ Neuronal degeneration or cerebellar responsible for the disease. PROGNOSIS & OUTCOME
abiotrophy • Urine assays
○ Neuraxonal dystrophy ○ Oligosaccharides and glycopeptides can • Poor
○ Cognitive dysfunction be profiled in urine samples using thin- • For most disorders, progressively worsening
• Anomalous layer chromatography to determine the neurologic signs lead to euthanasia within
○ Congenital hydrocephalus particular compound that is accumulating the first year of life.
○ Caudal occipital malformation syndrome and being excreted. • For those disorders with a slower progression,
○ Intracranial arachnoid cyst • Enzymatic assays progressive neurologic dysfunction leads to

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