- Autosomal recessive trait; due to lysosomal accumulation of sphingomylin resulting from inherited deficiency of sphingomyelinase.
- The accumulations take place in spleen, liver, lungs, bone marrow, and brain.
- A missense mutation causes complete deficiency of sphingomyelinase.
- 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:-
- Type A – Acute neuronopathic form
- Type B – Visceral form
- Type C – Chronic neuronopathic form
- Type D – Nova Scotia variant
- Type E – Adult form
- Type F – Sea-blue histiocyte disease
- Another classification divides this disease into –
- Type A – acute infantile form.
- Type B – less common, chronic, non – neurological form.
- Type C – biochemically & genetically distinct form
Niemann-Pick disease type A begins in the individual’s first few months of life. Symptoms include the following:
◦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
Tremors accompanying movement.
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.
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.
Shafers’ 8th edition