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