Niemann-Pick disease

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Gross appearance of a Miniature Poodle lung with Niemann-Pick disease, showing diffuse nodular appearance of lung on pleural and cut surface[1]

Niemann-Pick disease (NPD, Sphingomyelinosis, Sphingomyelin lipidosis) is an autosomal-recessive hereditary neurological disease of dogs characterized by neurologic dysfunction, hepatosplenomegaly, and early death[2].

Niemann-Pick disease is an inherited defect that results in the visceral and neuronal accumulation of sphingomyelin due to a deficiency in sphingomyelinase.

Humans exhibit five subtypes (A, B, C, D and E) that differ in age of onset, lesion distribution, and sphingomyelinase activity. Feline models of Niemann-Pick disease of subtypes A and C have been recognized[3], whereas in dogs, type C has been recognized in the Boxer[4] and Miniature Poodle[1].

Affected dogs show clinical signs at a few weeks of age which progress. The predominant clinical signs relate to nervous system dysfunction and usually predominate as cerebrocortical and cerebellar dysfunction. Symptoms include ataxia, hypermetria, continuous head shaking and loss of equilibrium.

However the neurologic signs at onset are variable and in some dogs are predominately neuromuscular with tetraparesis, hypotonia and areflexia developing between 2 and 5 months of age.

Diagnosis is based on clinical signs and histopathology and biochemical evidence of reduced sphingomyelinase enzyme activity including tissue accumulations of sphingomyelin, cholesterol and glycosphingolipids.

Histologically, there is vacuolation and granular distensions are seen in central nervous system neurones, glial cells, endothelium, choroid plexus, and ependymal cells. Macrophages with accumulations of granular material are referred to as Niemann-Pick cells and these are dispersed throughout the central nervous system and body organs, including the lung, spleen, renal lymph node, liver, adrenal gland and intestines.

Immunocytochemistry shows that both gangliosides GM3 and GM2 and unesterified cholesterol are differentially stored in neurons of the cerebral cortex, cerebellum, and hippocampus, as well as in liver[5].

A differential diagnosis would include cerebellar abiotrophy and other storage diseases such as globoid cell leukodystrophy, galactosialidosis, alpha-mannosidosis and gangliosidosis.

Treatment of individual cases is unrewarding and invariably lead to euthanasia. Alterations to diet in an attempt to lower blood cholesterol are uniformly unsuccessful.

References

  1. 1.0 1.1 Bundza A et al (1979) Niemann-Pick disease in a poodle dog. Vet Pathol 16(5):530-538
  2. Blakemore WF (1980) Neurolipidoses: examples of lysosomal storage diseases. Vet Clin North Am Small Anim Pract 10(1):81-90
  3. August, JR (2006) Consultations in Feline Internal Medicine, Vol 5. Elsevier Saunders
  4. Kuwamura M et al (1993) Type C Niemann-Pick disease in a boxer dog. Acta Neuropathol 85(3):345-348
  5. Zervas, M et al (2001) Neurons in Niemann-Pick disease type C accumulate gangliosides as well as unesterified cholesterol and undergo dendritic and axonal alterations. J Neuropathol Exp Neurol. 60(1):49-64