There are three types of Niemann-Pick disease that are all considered rare and under the broader category of Lysosomal Storage Diseases. The three types include: 

• Niemann-Pick Type A and B (ASMD or Acid Sphingomyelinase Deficiency) 
• Niemann-Pick Type C 

Niemann-Pick diseases (Types A, B and C) occurs when two copies of the mutated (defective) 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 if each parent is a carrier.  

Niemann-Pick diseases are 100% fatal and, in most cases, affect children of a very young age. Many children diagnosed in infancy, will not live to see their 10th birthday

Niemann-Pick disease type C (NPC) an ultra-rare and neurodegenerative disease caused by mutations in the NPC gene (NPC1 or NPC2). Mutations in NPC gene lead to reduced production of protein in cells responsible for transporting materials throughout the cell. When the protein is reduced, there is a toxic accumulation of lipids in the cells. NPC can be diagnosed at any age, however, more severe disease affects infants and young children. Diagnosing NPC can be difficult as young children may often appear healthy at birth and develop normally for several years – the exact number of years is variable for each child. Generally speaking, the younger a child is diagnosed with the disease the faster the disease progression is expected to be. Over time, development will slow, stop, then children begin to lose their skills and regress. Slowly the disease takes away a child’s ability to walk, talk and move. Eventually, swallowing and breathing becomes affected which often leads to death through complications such as aspiration and pneumonia. Presently NPC is always fatal and many children diagnosed early in life will not live to see their 10th birthday.  

Diagnosis 

If NPC is suspected or a medical condition is present and unknown, DNA testing may occur. DNA testing is available as single gene testing (if mutations are suspected or known in a specific gene), panel testing (may look at several genes that may contribute to a specific medical concern) or exome testing (looks at all the genes in the DNA). If mutations are identified in the NPC gene, this does not automatically mean they are disease causing. Secondary testing (skin biopsy or blood test) is often required to further confirm NPC disease. 

Diagnosis may also be confirmed by skin biopsy in Canada. A small piece of skin is removed and sent to a lab that will test to see if there is an accumulation of the lipids within the cell. These specialized labs are located in the United States so confirmation of diagnosis via skin biopsy can delay diagnosis for up to 6 weeks.  

In the United States, there is a blood test that can confirm a diagnosis of NPC however, this is not yet available in Canada.  

Symptoms 

With Niemann Pick Disease Type C (NPC), the onset of the disease can happen at any age. In many cases, the disease affects infants to school age children, however, it can also be diagnosed in adolescence and adulthood 

Symptoms May Include: 

• Jaundice at Birth or Shortly Afterwards
• Enlarged Liver and / or Spleen (Hepatosplenomegaly)
• Developmental Delay
• Hypotonia
• Difficulty with Upward & Downward Eye Movement (Vertical Supranuclear Gaze Palsy)
• 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)
• Psychosis (adult onset)

What is Niemann-Pick Disease Type C?

Niemann Pick Disease Type A (NPA) and Niemann Pick Disease Type B (NPB) were once thought to be separate diseases but are now understood to represent the wide spectrum of presentation of the same disease.  Acid Sphingomyelin Deficiency (ASMD)/Niemann Pick Disease type A & B is caused by a deficiency in an enzyme, acid sphingomyelinase (ASM). Acid Sphingomyelinase Deficiency (ASMD) is a very rare inherited lysosomal storage disorder. It is inherited when two copies of a faulty (mutated) SMPD1 gene on chromosome 11 are passed on to a child (autosomal recessive inheritance). The lack of adequate amounts of functional acid sphingomyelinase (ASM) results in harmful quantities of a fatty substance called sphingomyelin building up in the body’s cells causing cell death and malfunction of major organ systems.  The organ systems impacted may include the liver, spleen, lungs and brain.

Many variations exist in terms of clinical symptoms and rate of progression with some individuals having a very rapidly progressive decline with extensive neurological involvement (Type A), some having no neurological involvement (Type B) or those falling in the middle of the spectrum and exhibiting neurological problems which may become more apparent over time (Type A/B /intermediate type). Those diagnosed with Niemann Pick Disease Type A will typically not survive past age 5 years.  Those diagnosed with Type B will often survive into adulthood but not without experiencing health problems due to the disease.

ASMD is estimated to affect 1 in 250 000 individuals

ASMD/NPA symptoms typically develop within the first few months of life and may include:

• Swelling of the abdomen from enlargement of the liver and spleen (hepatosplenomegaly) by age 3-6 months of age
• Failure to Thrive
• Feeding difficulties
• Prolonged jaundice
• Interstitial lung disease resulting in lung infections and ultimate lung failure
• Progressive loss of early motor skills
• Cherry red spot identified on eye examination
• Rapid decline leading to death by two to five years of age

ASMD/NPB symptoms may include:

• Progressive enlargement of liver and spleen (hepatosplenomegaly)
• Poor Growth
• Susceptibility to respiratory infections
• Bleeding problems (bruising, thrombocytopenia)
• Bone pain
• Shortness of breath/pulmonary infiltrates on chest xray
• Cherry red spot identified on eye examination (up to 1/3 of patients)
• Age at diagnosis is quite variable

ASMD / NPA/B (intermediate type) symptoms may include:

• All of the items listed above for ASMD/NPB
• Neurologic symptoms that may become more apparent over time

What is ASMD Niemann-Pick Disease?
(Type A & B)