What are the other Names for this Condition? (Also known as/Synonyms)

• NPC2 (Niemann-Pick Disease Type C2)
• Niemann Pick Disease, Type C2

What is Niemann-Pick Disease Type C2? (Definition/Background Information)

• Niemann-Pick Disease Type C2 is a rare metabolic condition that affects many different parts of the body
• Although signs and symptoms can develop at any age (infancy through adulthood), most affected people develop features of the condition during childhood
• Neimann-Pick Disease Type C2 may be characterized by ataxia (difficulty coordinating movements), vertical supranuclear gaze palsy (inability to move the eyes vertically), poor muscle tone, hepatosplenomegaly (enlarged liver and spleen), interstitial lung disease, intellectual decline, seizures, speech problems, and difficulty swallowing
• Niemann-Pick Disease Type C2 is caused by changes (mutations) in the NPC2 gene and is inherited in an autosomal recessive manner
• There is no cure for Niemann-Pick Disease Type C2. Treatment is based on the signs and symptoms present in each person

(Source: Niemann-Pick Disease Type C2; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Niemann-Pick Disease Type C2? (Age and Sex Distribution)

• Niemann-Pick Disease Type C2 is a rare congenital disorder. The presentation of symptoms may occur at any age, although in most cases, symptom manifestation occurs in childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Niemann-Pick Disease Type C2? (Predisposing Factors)

• A positive family history may be an important risk factor, since Niemann-Pick Disease Type C2 can be inherited
• Currently, no other risk factors have been clearly identified for the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Niemann-Pick Disease Type C2? (Etiology)

• Niemann-Pick Disease Type C2 is caused by mutation(s) in NPC2 gene
• The causative gene mutation is inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Niemann-Pick Disease Type C2?

The signs and symptoms of Niemann-Pick Disease Type C2 may include:

• Abnormal cholesterol homeostasis
• Bone-marrow foam cells
• Cataplexy
• Dementia
• Fetal ascites
• Foam cells in visceral organs and CNS
• Generalized hypotonia
• Global developmental delay
• Hepatomegaly
• Loss of speech
• Low cholesterol esterification rates
• Neurofibrillary tangles
• Prolonged neonatal jaundice
• Psychosis
• Sea-blue histiocytosis
• Splenomegaly
• Stereotypy
• Vertical supranuclear gaze palsy

(Source: Niemann-Pick Disease Type C2; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Niemann-Pick Disease Type C2 Diagnosed?

Niemann-Pick Disease Type C2 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm NPC2 gene mutation(s) 

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Niemann-Pick Disease Type C2?

The complications of Niemann-Pick Disease Type C2 may include:

• Rapid progression of disease
• Severe neurological symptoms
• Respiratory failure

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Niemann-Pick Disease Type C2 Treated?

There is no cure for Niemann-Pick Disease Type C2, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Niemann-Pick Disease Type C2 be Prevented?

Currently, Niemann-Pick Disease Type C2 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Niemann-Pick Disease Type C2? (Outcomes/Resolutions)

• The prognosis of Niemann-Pick Disease Type C2 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• If it progresses rapidly with severe neurological and respiratory symptoms, the affected individuals may succumb to the disorder
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Niemann-Pick Disease Type C2:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/