What is Type A and B?

October is Niemann-Pick Disease Awareness Month.

WARNING - THIS POST CONTAINS LOTS OF MEDICAL TERMINOLOGY

Type A and B are significantly different than Type C.  These types are also known as Acid Sphingomyelinase Deficiency (ASMD).

Niemann-Pick Disease due to ASMD is inherited as an autosomal recessive condition. This means that affected individuals have two altered copies of the gene called SMPD1, having inherited one copy from each parent. Each unaffected parent (called a carrier) of an affected individual has one altered copy of the disease-causing gene and one normally-functioning copy of that gene. For a couple who are both carriers, there is a 1 in 4 chance with each pregnancy that a child will be affected by ASMD, a 2 in 4 chance that the child, like the parents,will be a carrier of ASMD, and a 1 in 4 chance that the child will be neither a carrier nor affected.

ASMD NPD occurs in all ethnic groups, but as with all genetic disorders may be more common in certain groups than others. For example, the severe, neurological form (Type A) appears to be more frequent among Ashkenazi Jewish individuals (carrier frequency of ~1:90 to 1:100).

Niemann-Pick Disease due to ASMD is usually classified into two groups: 1) Type A, in which affected individuals have severe neurological problems andusually do not survive past age 3, and 2) Type B, in which affected individuals do not have neurological problems and may survive into adulthood.

However, forms of ASMD NPD between these two extremes do occur, and the diagnosis is sometimes called Intermediate NPD A/B. There can be considerable overlap along the entire disease spectrum with symptoms ranging in onset, complexity and severity, and every patient’s case is unique.

The symptoms of ASMD NPD are shared by a number of related lysosomal disorders. Further, the rate of disease progression varies from patient to patient, even within families where more than one child is affected. This variability contributes to the challenges in diagnosis, and often leads to delay in confirmation of the diagnosis.

The first symptom in NPD-A is hepatosplenomegaly, usually noted by age three months; over time the liver and spleen become massive. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year.

NPD type B, later in onset and milder in manifestations than NPD type A, is characterized by hepatosplenomegaly with progressive hypersplenism and stable liver dysfunction, gradual deterioration in pulmonary function, and atherogenic lipid profile. Progressive and/or clinically significant neurologic manifestations occur infrequently. Survival to adulthood can occur.

Niemann-Pick Disease Type A (NPA)

Onset of symptoms very early, usually within the first few months of life

Enlarged liver and spleen

Feeding difficulties

Failure to Thrive (FTT)

Irritability

Progressive loss of motor skills, especially after one year of age

Cherry red spot on retina

Frequent respiratory infections

Niemann-Pick Disease Type B (NPB)

Later age at onset of symptoms

Enlarged liver and spleen in childhood

Gradually worsening lung function with susceptibility to respiratory infections

Altered blood lipid profile

Progressive evidence of cardiovascular and liver disease

Decreased platelet count

Delayed growth, short stature