Niemann-Pick disease type C2

Alternate names

NPC2

Definition

Niemann-Pick disease type C2 is a rare metabolic condition that affects many different parts of the body.

Onset

Although signs and symptoms can develop at any age (infancy through adulthood), most affected people develop features of the condition during childhood.

Epidemiology

Combined, Niemann-Pick disease types C1 and C2 are estimated to affect 1 in 150,000 individuals; however, type C1 is by far the more common type, accounting for 95 percent of cases.

Cause

Niemann-Pick disease type C2 is caused by changes (mutations) in the NPC2 gene . The proteins produced from NPC2 gene is involved in the movement of lipids within cells.

Gene mutations

• Mutations in these genes lead to a shortage of functional protein, which prevents movement of cholesterol and other lipids, leading to their accumulation in cells.
• Because these lipids are not in their proper location in cells, many normal cell functions that require lipids (such as cell membrane formation) are impaired.
• The accumulation of lipids as well as the cell dysfunction eventually leads to cell death, causing the tissue and organ damage seen in Niemann-Pick disease type C2.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

• 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.
• The manifestations in the perinatal period and infancy are predominantly visceral, with hepatosplenomegaly, jaundice, and (in some instances) pulmonary infiltrates.
• From late infancy onward, the presentation is dominated by neurologic manifestations.
• The youngest children may present with hypotonia and developmental delay, with the subsequent emergence of ataxia, dysarthria, dysphagia, and, in some individuals, epileptic seizures, dystonia, and gelastic cataplexy. Although cognitive impairment may be subtle at first, it eventually becomes apparent that affected individuals have a progressive dementia.

Diagnosis

Assay of oxysterols has largely replaced skin biopsy (see Clinical Description), and is now regarded as both a robust screening test and a first-line diagnostic test for NPC. The diagnosis of NPC is established in a proband with suggestive findings and biallelic pathogenic variants in either NPC1 or NPC2 identified by molecular genetic testing.

Treatment

• No curative therapy for NPC exists. Supportive therapy is provided by specialists from multiple disciplines including among others: neurology, physical therapy, occupational therapy, speech therapy, nutrition, feeding, psychology, social work, and medical genetics.
• Treatment with miglustat, approved for the management of neurologic manifestations of NPC in several countries but not the United States, has increased survival by five years from date of diagnosis or approximately ten years from onset of neurologic manifestations.[1].

NIH genetic and rare disease info

• NIH info on Niemann-Pick disease type C2

Niemann-Pick disease type C2 is a rare disease.

Niemann-Pick disease type C2 Resources
Need Help Finding a Doctor? Need help finding a doctor or specialist anywhere in the world? Explore our world directory. WikiMD's DocFinder can assist you in locating millions of physicians.	Medical Knowledge Access the latest research - Most recent articles Ongoing trials.

Translate to: East Asian 中文, 日本, 한국어, South Asian हिन्दी, Urdu, বাংলা, తెలుగు, தமிழ், ಕನ್ನಡ,
Southeast Asian Indonesian, Vietnamese, Thai, မြန်မာဘာသာ, European español, Deutsch, français, русский, português do Brasil, Italian, polski