Niemann Pick Type C is Ultra Rare

Rare and Ultra Rare Diseases

5-8% of the European population have a rare condition, which translates to 25-30 million people and up to 4 million in the UK. A number that is in fact higher than those affected by heart disease in this country! However, there are over 5,000 known rare diseases and that number is continually growing, which makes the numbers affected by an individual rare disease incredibly low (by definition a disease is rare if it effects less than 1 in 2,000 according to the European Union).

Niemann Pick C disease is defined as an ultra rare disease as there are less than 100 patients in the UK and only around 500 worldwide.

Rare diseases face the substantial challenge of gaining attention for their condition given the low numbers affected.

The prevalence (the measurement of all individuals affected by the disease within a particular period of time) of this ultra rare disease is quoted as around 1:120,000. In contrast, the most commonly inherited autosomal disease is Cystic Fibrosis (CF) which is described as a rare disease but whose prevalence is 1:2,500 . According to the CF web site there are currently over 8,500 people in the UK affected with CF.

Panethnic

NPC effects all population groups. It arises sporadically and with similar frequencies across all groups regardless of ethnic ancestry.

Autosomal, Recessive Disease

Autosomal: This simply refers to the fact that the mutations are not found on the sex chromosome. Human cells contain 23 pairs of chromosomes for a total of 46. There are 22 pairs of autosomes and one pair of sex chromosomes.

What does recessive mean?

Both parents have to be a carrier of a gene fault, giving a 1 in 4 chance of each pregnancy resulting with the child being affected with the disease.

autosomal_recessive

Why are NPC carriers not affected?

The lysosomal enzyme system has a lot of redundancy. 20% of normal enzyme activity is usually adequate to carry out cellular function. Therefore carriers, whose enzyme activity is 50% of normal, are clinically unaffected.

Neurodegenerative

The disease is characterized by a variety of progressive, disabling, neurological symptoms that can present in infants, children or adults. In children, first signs can be severe liver disease and/or respiratory failure. Other children can present with low muscle tone and developmental delay. The classic presentation occurs in mid-to-late childhood with the onset of unsteady movement, eye movement abnormalities and dementia (NPC is often referred to as "Childhood Alzheimers"). Involuntary muscle spasms and seizures are common. Dysarthria (a speech disorder- NPC patients tend to slur their speech) and difficulty in swallowing eventually becomes disabling, making oral feeding impossible. Aspiration pneumonia is the normal cause of premature death.

However, despite NPC being traditionally considered a childhood disease, today there are equal numbers of adults as children with the disease. This is due to improvements in diagnosis and increased awareness. Adults are more likely to present with dementia or psychiatric symptoms.

Despite the advances, the disease is still difficult to diagnose as the clinical manifestations of NPC are heterogeneous which means that there is no set path for this disease and it is even seen, though rarely, that patients within the same family, with the same inherited gene faults, can be impacted differently.