Niemann-Pick Disease – What is it?
There are three recognised forms of Niemann-Pick Disease, Niemann-Pick Type A, B and C. Niemann-Pick Type A and B are caused by an enzyme deficiency, causing a build up of toxic materials in the body's cells. Niemann-Pick Type C is not caused by an enzyme deficiency, but the end result is the same; an accumulation of materials (cholesterol and other fatty acids) in the body's cells.

In Niemann-Pick Type A this accumulation occurs very quickly, an affected child will usually die before reaching three years of age.

Niemann-Pick Type B does not affect the brain and, although growth may be slow, those affected will survive into adolescence or early adulthood, with many being able to lead a full and normal life.

In Niemann-Pick Type C, the brain and other organs are affected, leading to progressive intellectual decline, loss of motor skills, seizures and dementia. Speech can become slurred and swallowing problems may develop. The rate at which the disease progresses varies greatly between patients; children who develop neurological symptoms in early childhood are thought to have a more aggressive form of the disease, others may remain symptom free for many years.

If you or someone you know has been diagnosed as having, or suspected as having Niemann-Pick disease, it is likely that you are feeling overwhelmed with emotion and greatly confused as to what the disease is and how it has been acquired. The information provided on this website is intended to assist you and your family with understanding what the disease is and, hopefully, this will help in a small way in dealing with the distress that you inevitably feel and must face.

Why is it called Niemann-Pick?
The Niemann-Pick diseases are quite separate in terms of the fundamental cause but the similarities in clinical presentation have resulted in the naming of the diseases as Niemann-Pick, after two doctors who described the symptoms in the early part of the 20th century.

In 1914, a German paediatrician, Dr Albert Niemann, described the clinical presentation of children with the disease, but at that time little was known regarding the cellular or molecular explanation. Then, in the 1920's, the studies of Luddwick Pick provided evidence of a new disorder, one distinct from storage disorders previously described. Further investigations using cells taken from the tissues of affected individuals in the mid and latter years of the century, resulted in an improved understanding of the diseases and their cause. Since then there has been a considerable amount of investigation into these and other inherited diseases of metabolism.

It was not until 1958 that the disease presentations were classified into type A, B and C. In 1966 types A and B were identified with a lysosomal enzyme, acid sphingomyelinase. Type C, which in turn was further sub classified into types D, E and possibly others, remained the subject of investigation, mainly by the National Institute of Health near Washington, USA. Although NPC could be diagnosed through clinical, histological and biochemical means, it was not until 1997 that the genetic link was made which accounted for most of the NPC cases and is identified as NPC1. Subsequently, a further link was made with a second gene, NPC2, which accounted for most of the remainder. Some patients diagnosed with the disease remain to be accounted for. All known types of Niemann-Pick disease are acquired through autosomal recessive inheritance.

What causes Niemann-Pick disease?
In order to appreciate the cause of the disease, some basic understanding of the biology of the cell is needed. This is a complicated subject but it is worth investing a little time to learn about the basic components of the cell and gain a general understanding into how inheritance works. For those unfamiliar with the science, click here for an introduction to cell operations and the role of DNA (deoxyribonucleic acid) in inherited disease.

How does a person become affected by Niemann-Pick disease?

Niemann-Pick is an inherited disease. It is inherited in an autosomal recessive manner. In simple terms, this means that both parents have to be carriers of the faulty gene. In each pregnancy of a carrier couple, there is a 25% chance that they will pass on this gene mutation to their child.

Autosomes are the non-sex related chromosomes, and recessive indicates that the effects of possessing a single copy of a disease-causing gene are hidden. With a recessive condition, a person may be a carrier of a disease gene, but with no noticeable affect in their everyday lives and health. All types of NPD are autosomal recessive.

A positive diagnosis of say Niemann-Pick Type C disease in a child means that each of the parents is a carrier of a disease causing mutation on this gene. The mutations may be identical from each parent and the child will be referred to as homozygous for this mutation. In other instances the parental mutations will be different but disease causing and, the child will be referred to as heterozygous for the mutations. The homozygous condition may arise through intermarriage although this may not be obvious over many generations. Interbreeding may occur as a result of the isolation of a community possibly through geographic necessity or because of religious or cultural tradition.

Examples of the geographical isolation may be found in the USA and Canada and are due to a situation described as the founder effect. Communities of immigrants from Europe made their home in remote places on the American continent and had little contact with the outside world for many years. Unfortunately one or more of their members carried a recessive defective gene. This circulated down through the generations and gained in frequency as the population grew.

The Ashkenazi Jewish population is known to be at risk of higher than normal from certain inherited diseases such as Tay-Sachs and Niemann-Pick Type A. The reason for this is the cultural and religious practice of marrying within their own community. This tends to concentrate the disease gene frequency rather than dilute it. Communities with known problems are at least able to plan for carrier testing and take preventative measures. For the general population this cannot be done at present.

If a family is affected by Niemann-Pick disease apparently out of the blue, there is no way they could have prepared for the shock and no measure of prevention, which could have been planned. The tragedy is often compounded by the delayed disease onset. Children may not show symptoms for many years and diagnosis may itself take a number of years. Other children may have been born in this period and will each have a 25% risk of having the disease. There are, sadly, too many instances of families with more than one child affected. Further complications may arise where symptoms and diagnosis of the disease in an individual are delayed to adulthood and they have families of their own. The affect is that of a time bomb. Once a diagnosis has been obtained in a family then they will be acutely aware that they are at risk in terms of having further children. In addition other members of the family will be concerned and wonder if they too, could be affected.

Niemann-Pick diseases are Lysosomal disorders, of which there are approximately 40 different types. Most of the identified diseases are either named after the doctor who first described the clinical symptoms or the cellular/molecular basis or, the scientific name that is most appropriate. In the latter case most of the names are unpronounceable without practice. The incidence of each disease ranges from one in a few hundred to one in many thousands or even millions. Individually each of the diseases is classified as rare by medical authorities but taken as a whole, they are epidemic proportions. It has been observed that there seems to be a lot of rare diseases. The miracle is that any of us function at all!