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Niemann-Pick disease

Contents

  • 1 Introduction
  • 2 Clinical signs
  • 3 Diagnosis
  • 4 Pathological features
  • 5 References

 

Introduction

Niemann-Pick disease (NPD) or Sphingomyelin lipidosis is a neurovisceral lysosomal storage disease characterized by neurologic dysfunction, hepatosplenomegaly, and early death. NPD is an inherited defect that results in the visceral and neuronal accumulation of sphingomyelin. Human beings exhibit five subtypes (A, B, C, D and E) that differ in age of onset, lesion distribution, and sphingomyelinase activity. Feline models of Nieman-Pick disease of subtypes A and C have been recognised.

 

Clinical signs

Clinical signs predominate as cerebrocortical and cerebellar dysfunction. Cuddon, Higgins, Duncan et al[1] described three cats with chemical changes consistent with type A Nieman-Pick disease that have predominant clinical signs of peripheral nerve dysfunction. Tetraparesis, hypotonia and areflexia develop between 2 and 5 months of age. Spontaneous activity is detected with needle electromyography and motor and sensory conduction velocities are markedly slow. Light microscopy of peripheral nerves show severe demyelination and remyelination with vacuolated macrophages surrounding affected nerve fibres. Vacuolation and granular distensions are seen in neurones, glial cells, endothelium, choroid plexus, and ependymal cells. Macrophages with accumulations of granular material were dispersed throughout the central nervous system and body organs.

 

Diagnosis

Diagnosis is based on clinical signs and histopathology and biochemical evidence of reduced sphingomyelinase enzyme activity including tissue accumulations of sphingomyelin, cholesterol and glycosphingolipids. In one reported case[2], a 7-month-old Balinese cat with progressive neurological dysfunction had histopathological lesions of brain, liver, kidney, spleen, and lung consistent with a lysosomal storage disease. Ultrastructural examination revealed lysosomal hypertrophy with membranous inclusions. Hepatic sphingomyelin and cholesterol were elevated 10 times normal, and total phospholipids were increased 3.6 fold. Sphingomyelinase activity measured with 14C labeled sphingomyelin at pH 5.0 was virtually absent in brain and liver. Other lysosomal hydrolase activities were normal or elevated. Clinical, morphological, and biochemical findings suggested that this cat had sphingomyelin lipidosis similar to human Niemann-Pick disease type A, and that feline sphingomyelin lipidosis provides another model of human lysosomal storage disease.

 

Pathological features

Pathologically characterized by “knife-blade” atrophy of the frontal and temporal lobes in humans. Very marked neuronal loss and gliosis in areas with ballooned neurons and intracytoplasmic Pick bodies. Recent research has uncovered mutations in microtubule associated protein (tau) on Chromosome 17 in some human families. Niemann-Pick disease is caused by a deficiency in sphingomyelinase which leads to accumulation of sphingomyelin in the cytoplasm of macrophages. The globules are small and relatively uniform in size, sometimes described as mulberry-like in appearance. Foamy macrophages similar to Niemann-Pick cells may be seen in any disorder that is associated with massive cell destruction that overloads the capacity of the cellular machinery to digest lipids (e.g., thalassemias, sickle cell anemia, ITP, chronic renal failure).5 The vacuoles may be larger and more irregular in size than those seen in true Niemann-Pick cells. As compared to Gaucher cells, the cytoplasm in these macrophages is foamy and vacuolated as opposed to fibrillary. Sea blue histiocytes may be found in small numbers in normal bone marrow. They are increased in any disorder associated with massively increased intramedullary cell destruction, such as chronic myelogenous leukemia. The macrophage cytoplasm is filled with insoluble lipid pigment, called ceroid, which is thought to represent partially digested globosides derived from cell membranes.5 As compared to Gaucher cells, these cells stain more intensely blue with Wright-Giemsa and the inclusions are globular rather than fibrillary[3].

 

References

1. August, JR (2006) Consultations in Feline Internal Medicine, Vol 5. Elsevier Saunders

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