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)

Niemann Pick disease type A (NPA) and B (NPB) is collectively known as Acid Sphingomyelin Deficiency (ASMD) and is caused by mutations in the SMPD1 gene. Mutations in SMPD1 lead to a deficiency of acid sphingomyelinase (ASM). When deficient, there is a reduced break down of sphingomyelin, causing accumulation in cells. This accumulation becomes toxic causing cell dysfunction and death.  

 Those diagnosed with NPA will have little to no acid sphingomyelinase enzyme and therefore sphingomyelin builds up in the body’s cells, organs and in the brain and has resulting aggressive neurological involvement.  Children diagnosed with NPA will typically not survive past age 3 years.  

 Those diagnosed with NPB will have about 10% of acid sphingomyelinase enzyme production. In NPB, the build of material is mainly in the lungs, liver and spleen. NPB does not affect the brain and those affected will often survive into adulthood and may lead very normal and active lives. 

 Some patients diagnosed are found to fall within the middle of the spectrum of ASMD and may exhibit slower neurological involvement.  

 ASMD is estimated to affect 1 in 250,000 individuals.  

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.