Niemann-Pick Disease Type C

Niemann-Pick Type C (NP-C) is a rare inherited neurodegenerative disease that affects infants, children and adults. It is caused by an accumulation of lipids (fats) in the liver, brain and spleen. The age of onset and rate of disease progression can vary greatly from person to person; for example some children develop neurological symptoms early in childhood, whereas others may remain symptom free for a number of years.

It is inherited when two copies of a faulty gene (a mutation) are passed on to a child. In every pregnancy of a couple who each carry a copy of the faulty Niemann-Pick gene, there is a 1 in 4 chance (25%) that their child will have Niemann-Pick disease. This is known as autosomal recessive inheritance.

NP-C is divided into two subtypes, NP-C1 and NP-C2, as each is caused by a different gene mutation. Approximately 95 per cent of NP-C cases are caused by genetic mutations in the NP-C1 gene, with the other five per cent caused by mutations in the NP-C2 gene.

The incidence of NP-C is widely reported at 1  in 120,000, although recent evidence suggests  this may be an under-estimate.

Niemann-Pick Disease Type C (NP-C) is caused by an accumulation of cholesterol and other fatty substances in the liver, brain and spleen.

Niemann-Pick Disease Type C (NP-C) is difficult to diagnosis as the symptoms are non-specific to the disease and will vary from person to person. NP-C is diagnosed by taking a small piece of skin (a skin biopsy) to see whether there is accumulation of fatty substances within the cells.

Diagnosis can also be made via a DNA analysis if the mutations in the affected child are known. This can be done fairly simply on a blood test but is only carried out in a few specialist centres.

Symptoms of Niemann-Pick Disease Type C (NP-C) vary with age of onset and from patient to patient.They may include:

• Jaundice at (or shortly after) birth
• An enlarged spleen and/or liver (hepatosplenamegaly)
• Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy)
• Unsteadiness of gait, clumsiness, problems in walking (ataxia)
• Difficulty in posturing of limbs (dystonia)
• Slurred, irregular speech (dysarthria)
• Learning difficulties and progressive intellectual decline (cognitive dysfunction/dementia)
• Sudden loss of muscle tone which may lead to falls (cataplexy)
• Tremors accompanying movement and, in some cases, seizures
• Swallowing problems (dysphagia)

There is no cure for Niemann-Pick Disease Type C (NP-C), although patients benefit from palliative treatments (individual medications that will help to treat the symptoms related to the condition). Occupational therapy can be used to help with posture, speech and movement.

In 2009, the European Medicines Agency approved the use of Zavesca© for the treatment of progressive neurological manifestations in adult and paediatric patients with NP-C.  Zavesca© has been shown to delay the progression and stabilise certain symptoms of the disease. However, this drug is not suitable for every affected individual and you are advised to discuss all medical issues with your doctor.

There are a number of clinical trials currently taking place investigating new therapeutic options for patients with NP-C.