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945.e2 Storage Diseases

Storage Diseases
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Deficiency
BASIC INFORMATION
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Deficiency: N-acetylglucosamine-1-
❏ Type A: sphingomyelinase ○ Mucolipidosis II (I-cell disease)
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Definition ❏ Type B: cholesterol esterification phosphotransferase
Inherited disorders can result in intracellular deficiency ■ Clinical signs: not well described
accumulation of specific storage product(s) ❏ Type C: NPC1 mutation ○ Mucopolysaccharidosis type VII (Sly
due to a deficiency in an enzyme or cofac- ■ Clinical signs: ataxia, head tremors, disease)
tor necessary for further metabolism of the paraparesis, weight loss, depression ■ Deficiency: beta-D-glucuronidase
substance. The accumulated storage products • Glycoproteinoses ■ Clinical signs: not well described;
cause cellular dysfunction. This discussion is ○ Fucosidosis skeletal deformities, ataxia, corneal
limited to the lysosomal storage disorders, in ■ Deficiency: alpha-L-fucosidase cloudiness
which the substance that fails to be processed ■ Clinical signs: initially, forebrain dys- • Proteinoses
accumulates in lysosomes. function predominates and progresses ○ Ceroid lipofuscinosis (Batten disease)
over 2-3 years to include ataxia, ■ Deficiency
Synonym dysphagia, vision and hearing loss, ❏ Cathepsin D
Lysosomal storage disorders nystagmus, and dysphonia. ❏ Neuronal ceroid lipofuscinosis type
❏ Relatively late onset of clinical 5 (CLN5)
Epidemiology signs; neurologic dysfunction begins ❏ Neuronal ceroid lipofuscinosis type
SPECIES, AGE, SEX between 12 and 18 months of age. 2 (CLN2) disease, caused by a muta-
• Dogs and cats ❏ Palpable enlargement of the ulnar tion in the tripeptidyl peptidase 1
• Age of onset varies; typically normal at birth nerves secondary to edema and infil- gene (TTP1)
and develop clinical signs in first several tration with lipid-filled phagocytes ❏ Neuronal ceroid lipofuscinosis type
weeks to months of life and Schwann cells 8 (CLN8)
• Signs may not become apparent until much ○ Mannosidosis ■ Clinical signs: behavioral changes and
later in life. ■ Deficiency: alpha-D-mannosidase visual deficits seen initially; progresses
• No known sex predisposition ■ Clinical signs include skeletal abnor- over several years to include seizures,
malities, ataxia, head tremor, and ataxia, tremors, and hypermetria
GENETICS, BREED PREDISPOSITION possibly gingival hyperplasia. ❏ Encephalopathic signs usually first
• Generally have an inherited basis (mostly ○ Neuronal glycoproteinosis (Lafora disease) seen at 1-2 years of age (range of
autosomal recessive) ■ Deficiency: laforin (a glycogen phos- disease onset, 6 months to 10 years)
• Can occur as spontaneous mutation phase), malin (an ubiquitin ligase) ❏ A form of ceroid lipofuscinosis
Clinical signs: forebrain dysfunction selectively involving the cerebellum
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RISK FACTORS predominates in the first year of life. and thalamus has been described in
Affected relatives or breeds that are at risk (see ○ Galactosialidosis dogs.
Suggested Readings and Storage Disorders) ■ Deficiency: protective protein/cathepsin ❏ Cats typically demonstrate rapid
A neurologic decline.
Clinical Presentation
■ Clinical signs: predominantly ataxia • Oligosaccharidoses
DISEASE FORMS/SUBTYPES • Mucopolysaccharidoses ○ Glycogenosis type 1a
• Sphingolipidoses ○ Mucopolysaccharidosis type I (Hurler ■ Deficiency: glucose-6-phosphatase
○ Globoid cell leukodystrophy (Krabbe syndrome) ○ Glycogenosis type II (Pompe disease)
disease) ■ Deficiency: alpha-L-iduronidase ■ Deficiency: alpha-glucosidase
Deficiency: beta-D-galactocerebrosidase Clinical signs: predominantly pelvic ○ Glycogenosis type IIIa
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Clinical signs: multifocal; predomi- limb gait disorder without overt Deficiency: glycogen debranching
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nantly ataxia, pelvic limb paresis/ neurologic deficits; patients can have enzyme (AGL gene)
paralysis; cerebellar dysfunction can hyperextensible joints and plantigrade ○ Glycogenosis type IV (Andersen disease)
be the predominant early sign stance; skeletal and craniofacial abnor- ■ Deficiency: glycogen debranching
○ GM 1 gangliosidosis (Norman-Landing malities can be present. enzyme
disease) ○ Mucopolysaccharidosis type II (Hunter
Deficiency: beta-galactosidase disease) HISTORY, CHIEF COMPLAINT
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Clinical signs: multifocal; predomi- Deficiency: iduronate-2-sulfatase • Normal at birth
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nantly cerebellar dysfunction; can ○ Mucopolysaccharidosis type III (Sanfilippo • Clinical signs typically become apparent
progress to tetraplegia syndrome) within the first 6 months of life and slowly
○ GM 2 gangliosidosis (Derry disease) ■ Type IIIA: heparan sulfate sulfamidase progress over 1 to 2 years.
Deficiency: beta-galactosidase deficiency • Intention tremors are a common chief
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Clinical signs: multifocal; predomi- Type IIIB: N-acetyl-alpha-D-glucosa- complaint.
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nantly cerebellar dysfunction; can minidase deficiency • Specific presenting complaints depend on
progress to tetraplegia ■ Clinical signs: not well described; the particular storage disease.
○ Glucocerebrosidase deficiency (Gaucher predominantly tremors and ataxia • Can have familial history of disease
disease) ○ Mucopolysaccharidosis type VI (Marote-
Deficiency: beta-D-galactocerebrosidase aux-Lamy syndrome) PHYSICAL EXAM FINDINGS
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Clinical signs: multifocal; predominantly Deficiency: arylsulfatase B • General physical exam is typically
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cerebellar ataxia, tremors, hyperactivity ■ Clinical signs: predominantly skeletal unremarkable.
○ Sphingomyelinase deficiency (Niemann- malformations (kyphosis, facial defor- • Neurologic exam findings depend on the
Pick disease) mities); upper motor neuron paraparesis specific storage disease; findings can include
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