Types of Niemann Pick Disease

Types of Niemann Pick Disease

There are three types of Niemann-Pick Disease. Types A and B (ASMD or Acid Sphingomyelinase Deficiency) and Niemann-Pick Disease Type C (NPC).

  • Type A and B (ASMD or Acid Sphingomyelinase Deficiency) are known as Type 1
  • Type C (C1 & C2) is known as Type 2

Overview of Niemann-Pick Disease Type A & B (NPA & NPB)

Niemann-Pick Type A (NPA) and Type B or (ASMD), is caused by the deficiency of a specific enzyme, acid sphingomyelinase (ASM). This enzyme is found in special compartments within cells called lysosomes– required to metabolize a lipid called sphingomyelin.

If ASM is absent or not functioning properly, sphingomyelin cannot be metabolized properly which accumulates within the cell.

There is growing evidence that the two forms (NPA & NPB) represent opposite ends of a continuum. People with NPA generally have little or no ASM production (less than 1% of normal). Those with NPB have approximately 10% of normal level of ASM.

In NPA, sphingomyelin builds up in the body’s cells, organs and in the brain, resulting in aggressive neurological involvement. Type A children display the symptoms earlier on in life (infancy). Children with NPA do not typically survive past early childhood (age 3).

In NPB, sphingomyelin builds up mostly in the liver, spleen and lungs. Type B will occur later on in mid childhood. Type B may also have milder symptoms than Type A children. Individuals with NPB can typically survive into adulthood.

Every patient’s case is unique. There can be considerable overlap along the entire ASMD disease spectrum with symptoms ranging in onset, complexity and severity.

NPA Symptoms May Include:

  • Enlarged liver and spleen (hepatosplenomegaly) by age 3 months
  • Failure to thrive
  • Psychomotor regression at age 1 (progressive loss of abilities – mental and physical)
  • Interstitial lung disease resulting in lung infections and ultimate lung failure
  • Cherry-red spot identified with eye examination (all affected children)

NPB Symptoms May Include:

  • Symptoms outlined under NPA (but less severe)
  • Thrombocytopenia (low number of platelets)
  • Short stature
  • Cherry-red spot identified with eye examination (⅓ of affected children)

Diagnosis for NPA & NPB

NPA and NPB are diagnosed by measuring the level of acid sphingomyelinase (ASM) activity in white blood cells. To do the test, a small blood sample is needed from an individual suspected of having the disease. This test is available at many commercial laboratories.

Molecular genetic testing is also commercially available for Niemann-Pick Disease.

More information to come.

Overview of Niemann-Pick Disease Type C

Niemann-Pick Disease Type C also known as NPC is a fatal, neurodegenerative disease that affects 1 in 120,000 (however these numbers are growing). It affects people of all ages from newborns to adults.

NPC is a rare genetic disease where lipids (fats) build up in the liver, spleen and brain – impeding the organs from functioning properly. NPC affects everyone differently and the severity of the symptoms vary from individual to individual. The onset of the disease may be aggressive in some, while in others, it may be dormant for many years.

Autosomal Recessive Inheritance

Niemann-Pick Type C occurs when two copies of the mutated gene (one from the father and one from the mother) are passed along to their child. There is a 1 in 4 chance a child will inherit both mutated genes of each parent is a carrier.

Autosomal Recessive Inheritance

Sub Types of NPC

NPC has two sub types NP-C1 and NP-C2 (caused by different gene mutations). 95% of NPC cases are NP-C1 gene mutations whereas, 5% are NP-C2 gene mutations.

Causes

Niemann-Pick Type C NPC is an inherited, rare, lipid storage disease. It interferes with the the ability to process cholesterol properly – lipids (fats) accumulate in the liver, spleen and brain. NPC is a fatal lysosomal disease sometimes referred to as Childhood Alzheimer’s.

 

Niemann_pick_cell_in_spleen

Niemann_pick_cell_in_spleen

Diagnosis

Unfortunately, Niemann-Pick Type C (NPC) is very difficult to diagnose. Many symptoms may mimic other types of diseases. NPC can be misdiagnosed and/or subtle signs can be missed. Symptoms and cell deterioration can occur at different rates and in different age groups.

To determine if you or someone in your family has NPC, a skin biopsy test is required in Canada. This can be a lengthy diagnosis of up to 6 weeks as only specialized centres can complete this particular test.

Diagnosis for NPC

You can also opt for a blood test that can confirm diagnosis (to replace the skin biopsy test), however, this is not yet available in Canada. Other tests include a DNA analysis of a blood sample (this test is only available at specialized health centres).

Symptoms

Each person is different – one person may experience all the symptons to the utmost severity, while another may experience a few symptoms mildly and slowly progressive.

With Niemann Pick Disease Type C (NPC), each case is very unique. The onset of the disease can happen at any age. In many cases, the disease affects infants to school age children. However it has also been found in adults – the disease being dormant for most of their lives.

Symptoms May Include:

  • Jaundice at Birth or Shortly Afterwards
  • An Enlarged Spleen or Liver (Hepatosplenomegaly)
  • Difficulty with Upward & Downward Eye Movement (Vertical Supranuclear Gaze Palzy)
  • Unsteadiness with Gait, Clumsiness or Walking (Ataxia)
  • Poor Posture Due to Difficulty with Posturing of Limbs (Dystonia)
  • Slurred Irregular Speech (Dysarthria)
  • Learning Difficulties & Progressive Intellectual Decline (Cognitive Dysfunction/Dementia)
  • Sudden Loss of Muscle Tone Which May Lead to Unexpected Falls (Cataplexy)
  • Tremors Accompanying Movement
  • Seizures
  • Swallowing Problems (Dysphagia)

Treatments

At this time there is NO cure for Niemann Pick Disease Type C (NPC). But there is still hope – through clinical trials of new therapies, a cure is possible.

Zavesca© (Migulstat) is indicated for children and adults in Canada diagnosed with Niemann Pick Disease Type C. It has shown to stabilize and delay the neurological manifestations of the disease from progressing.

All treatment options must be discussed with your doctor. This treatment may not be available in your local area and it may not be suited to all persons with NPC.

Patients with NPC may benefit from a variety of treatment options to manage symptoms during the course of the disease such as speech therapy, physiotherapy, occupational therapist, respiratory therapy etc.

It’s all very scary and it may feel confusing to understand – how this can happen to your beautiful child.

But there is hope! NP Canada is here to help you find the support you need to tackle this head on.

Contact us at anytime.

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