Niemann – Pick Disease

  1. Autosomal recessive trait; due to lysosomal accumulation of sphingomylin resulting from inherited deficiency of sphingomyelinase.
  2. The accumulations take place in spleen, liver, lungs, bone marrow, and brain.
  3. A missense mutation causes complete deficiency of sphingomyelinase.
  4. The enzyme deficiency block degradation of lipid, resulting in the accumulation of sphingomyelin within lysosomes in the macrophage-monocyte phagocyte system.
  • The following 6 types of Niemann-Pick disease have been described:- 
  1. Type A – Acute neuronopathic form
  2. Type B – Visceral form
  3. Type C – Chronic neuronopathic form
  4. Type D – Nova Scotia variant
  5. Type E – Adult form
  6. Type F – Sea-blue histiocyte disease
  • Another classification divides this disease into –
  1. Type A – acute infantile form.
  2. Type B – less common, chronic, non – neurological form.
  3. Type C – biochemically & genetically distinct form

Clinical Features:-

  • Niemann-Pick disease type A begins in the individual’s first few months of life. Symptoms include the following:

    ◦Feeding difficulties

    ◦Abdominal enlargement within 3-6 months

    ◦Progressive loss of early motor skills

    ◦Rapid decline leading to death by the time the patient is aged 2-3 years

  • Niemann-Pick disease type B is similar to Niemann-Pick disease type A, but the symptoms are more variable.

    ◦Abdominal enlargement may be detected in early childhood.

    ◦Respiratory infections recur.

    ◦No neurologic involvement is present.

  • Niemann-Pick disease type C usually affects school-aged children, but the disease may occur at any time from early infancy to adulthood.

Symptoms may include the following:

◦Unsteadiness of gait, clumsiness, problems in walking

◦Difficulty in posturing of the limbs

◦Slurred, irregular speech

◦Learning difficulties and progressive intellectual decline

◦Sudden loss of muscle tone, which may lead to falls

◦Seizures

Tremors accompanying movement.

Histologic features:-

  • Niemann  – Pick cells are foamy, lipid – laden cells distributed throughout RES.

  • Positive for cholesterol & only weakly positive for ALP.

  • Affected cell becomes extremely large, enlarged secondary to distention of lysosomes.

Treatment:-

  • Enzyme replacement therapy currently being explored.

  • Current treatment symptomatic; consists mainly of antibiotic therapy for infections of pulmonary involvement.

  • Organ transplant (liver) also proposed

  • Overall prognosis poor.

References:-

Shafers’ 8th edition

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