Niemann-Pick Disease: Types, Causes, Symptoms, Diagnosis, Treatment, Prognosis, Prevention

Niemann-Pick Disease is a group of genetic conditions, which affects the metabolism of fats or lipids in the body. In this inherited condition, there is deficiency of a lysosomal enzyme called acid sphingomyelinase or disturbance in cholesterol breakdown or transportation. This enzyme is responsible for proper metabolism of lipids and lack of it, affects lipid metabolism.

In short, the way in which the body stores and removes lipids, i.e.. fats and cholesterol is affected, resulting in abnormal collection of fats in important organs. It affects main organs like the liver, spleen, brain and bone marrow.

Niemann-Pick Disease is primarily classified into four main types based on the genetic changes and the clinical presentation.

• Type 1 – This includes Niemann-Pick Disease Type A and Niemann-Pick Disease Type B
• Type II – This includes Niemann-Pick Disease Type C and Niemann-Pick Disease Type D

These types have different causes to produce the effect of the disorder.

• Causes of Niemann-Pick Disease Type A and B – There is absence or improper functioning of the enzyme called acid sphingomyelinase, which is responsible for metabolizing a fat substance called sphingomyelin, found in the body cells. The defect is found in a gene located on chromosome 11. As the fat substance is not properly broken down, it gets excessively built up within the body cells, causing cell death. This, eventually affects the organ functioning.
• Causes of Niemann-Pick Disease Type C – The body is unable to breakdown the cholesterol and other lipids properly. This leads to excess build up of cholesterol in liver and spleen. Excess amount of lipids also get accumulated in the brain.
• Causes of Niemann-Pick Disease Type D – The body shows a defect in the movement and transportation of cholesterol, which affects its movement between the brain cells. It is considered as a variant of Type C.

The four types of Niemann-Pick Disease have different clinical picture. The symptoms may vary in these types and may range from being asymptomatic to having a typical picture.

Patients with this type may typically have normal appearance at birth but may show symptoms during early months of life. These may include:

• Enlarged liver and spleen or swelling in abdomen by around 3 months, which may progress with age.
• Feeding issues, failure to thrive
• Frequent respiratory infections
• Red spot in the eye
• Irritability.

On examination, mild hypotonia may be noted by around 6 months, which may worsen with age. It can progress into loss of tone and deep tendon reflexes. Developmental delays are noted and there may be further loss of motor function and impairment of intellectual capacity. Sometimes, one-sided tremors may be seen.

Clinical features in this case may appear milder. These include:

• Enlargement of liver and spleen or abdominal swelling, which may be noticed during a routine check-up during childhood. In mild cases the enlargement may not be noticed until adulthood.
• Lung infections and recurrent respiratory infections may be noted.
• Some may show neurological involvement, poor co-ordination and impaired intellectual capacity
• In severe cases, liver involvement is marked with cirrhosis and ascites.

Clinical features of this type usually affect middle-aged children. The symptoms include:

• Enlarged liver and spleen with jaundice in newborns
• Loss of muscle tone with difficult to move limbs and increased risk of falling
• Neurological involvement with unsteady walk, clumsiness and trouble moving eyes vertically.
• Tremors, seizures and slurred speech may also be noted
• Impairment of intellectual abilities, learning difficulties.

Symptoms appears similar to type C.

Confirmed diagnosis is made by performing investigations that measure the enzyme activity,

• To Diagnose Niemann-Pick Disease Type A and B – Blood test and bone marrow aspiration
• To Diagnose Niemann-Pick Disease Type C and D – Skin biopsy to detect the storage and transport of cholesterol within the cells
• To Detect Carriers of Niemann-Pick Disease – DNA analysis.

• Blood Tests – To detect pancytopenia (due to enlarged spleen), enzyme assays, elevated transaminase levels, increased levels of cholesterol, triglycerides and other lipids.
• Chest X –Ray – To detect the presence of infiltration and pulmonary nodules.
• Pulmonary Function Test (PFT) – To determine oxygen diffusion and exercise tolerance.

Treatment for Niemann-Pick Disease Type A – This type does not have specific effective treatment at present and symptomatic approach is followed. Surgical treatment options like liver transplantation in infants are being researched.

Treatment for Niemann-Pick Disease Type B – Increased blood cholesterol levels are maintained within desirable range with medications like statins and liver function is regularly monitored. In case of bleeding episodes, blood products transfusion may be considered. Pulmonary diseases or interstitial lung disease may be managed with supplemental oxygen. Surgical treatment may have some positive results with patients who have undergone bone marrow transplant, but may not be advisable for patients with neurological involvement.

Treatment for Niemann-Pick Disease Type C – A novel enzyme inhibitor drug may be considered if found appropriate by the treating physician.

Treatment for Niemann-Pick Disease Type D – This type does not have specific treatment at present and symptomatic treatment is given.

The prognosis varies according to the type, but generally Niemann-Pick Disease Type A, C and D may be fatal during childhood years, while patients with type B may survive into adulthood.

While the effect of diet is not very clear, patients may be advised to consume a low cholesterol or fat free diet. Support groups can help families with relevant information and coping with the condition.

Genetic counseling for couples having a family history is advisable. Detection of carriers should also be considered if the genetic defect is known.