Niemann-Pick disease

Niemann-Pick disease is an autosomal recessive hereditary lysosomal storage disease, caused by specific genetic mutations. sphingolipids. It is included within the group of lipidosis, which are lipid storage diseases.

History

Niemann Pick's disease was first described in 1914 by the German pediatrician Albert Niemann (born February 23, 1880 in Berlin, where he died on March 22, 1921) in children of Jewish origin (Ashkenazes), an ethnic group from central and eastern Europe; and in 1927 Ludwig Pick (born August 31, 1868 and died February 3, 1944) already as its own entity differentiated from other diseases, in a tissue study differentiating it from Gaucher disease.

To Crocker we owe the distinction, in 1961, of the four types that we study today (A, B, C and D).

Finally, we will mention that it was Brady who isolated the lysosomal enzyme sphingomyelinase in 1966, whose deficiency produces types A and B. Types C and D are caused by a defect in the intracellular transport of cholesterol that accumulates in its free form without esterify.

Classification

All four forms of Niemann-Pick disease are characterized by an accumulation of sphingomyelin and cholesterol in the lysosomes of cells, particularly in cells of major organs such as the liver and spleen. The three best-known forms of the disease are types A, B, and C.

• La Type A It is rare, characterized by its early appearance of the disease, it is very serious, almost incompatible with life, die within a few months and rarely survive the first year of life.

• La Type B is another manifestation of the disease, the affected organ is the lungs, are neurologically normal people, usually have an acceptable longevity.

• La Type C Niemann-Pick disease is neurological and visceral expression. It is manifested with a marked neurological deterioration and to a lesser extent a hepato-splenic affectation. It has two forms of presentation: one infantile or early, with a life expectancy that does not exceed the first decade of life, and another juvenile, with the same symptoms, but with a life prospects between the second and third decade of life.

• La Type D It is very similar to type C in its manifestations, considering itself an allelelic variant, in Nova Scotia, Canada.

There is no clear relationship with the sphingomyelinase deficiency in type C, there is a genetic origin caused by the anomaly in what are called, in avant-garde terms, regulatory genes. It is also related to a very specific protein related to intracellular cholesterol homeostasis. This deposit will cause an alteration in the cells, deteriorating them, deforming them (spongy cells) and ending in their death. The organic substrates where this cell lysis will affect, are primarily in order of importance: brain, liver and spleen. As these are the affected organs, the clinical expressions of this disease will come from there.

Clinical picture

This disease causes a progressive deterioration in vital functions, such as:

• Loss of the ability to speak.
• Paulatine loss of walking ability.
• Difficulty in intellectual activity.
• Difficulties swallowing food.
• Respiratory insufficiency.
• Progressive disconnect from the environment around them.

Children with it die early in the first three years of life. Characteristics of the disease are infantilism and developmental disorders. Swollen cells will appear in the cerebral cortex with the Baker stain technique, called xanthomatous cells. Other signs are hepatosplenomegaly, anemia, bone marrow disorders, as well as disorders of the growth plates of the long bones.

Diagnosis

The diagnosis of Niemann Pick disease is confirmed with enzymatic studies and with a biopsy of the patient's skin; at the same time, there are molecular studies that determine the genetic type of the disease.

If a child is born with some type of Niemann-Pick (A, B, C) it is because both parents carry the abnormal gene that produces it, even though they themselves do not have symptoms of the disease; this is because all types are autosomal recessive.

When the parents are carriers, it is more likely (50%) that the child will be born a carrier of the disease than sick (25%), which is why there are few cases of this rare disease.

Carrier screening in families is still unreliable. But for type A and B mutations, DNA tests are available, as they have been extensively studied, especially in the Ashkenazi Jewish population.

DNA mutations have been found in type C patients and with this, it is possible to find the carrier. Few medical centers already have a fetal diagnosis for Niemann-Pick.

Many of the symptoms produced by the disease are common to other diseases and this makes it difficult to diagnose with certainty. Doctors advise that if the disease is suspected in types A and B, a "measurement of acid sphingomyelinase activity in white blood cells" be performed. This is done by doing a blood test or foam cell biopsy in the bone marrow. This test is ineffective in detecting carriers. When the disease is type C, it is diagnosed by performing a skin biopsy, “cell culture in the laboratory and subsequent study of the capacity of the isolated cells to transport and store cholesterol. Additional diagnostic tests include slit-lamp eye examination, bone marrow aspiration, and liver biopsy.

Scientists cannot explain why there are so many differences in the course of the disease. Purely statistical data reveals that a child with type C symptoms before they are one year old does not reach school age, but if they develop symptoms after school, they live until their mid to late teens, very few reach the age of 20. Although types A and B have the same cause, a person with type A dies around the age of 2 or 3, while type B can live into adulthood.

Throughout Spain there are around 20 families affected by NP and they hold meetings and conferences about the disease to discuss and carefully analyze possible preventive treatments for the disease that, being classified as "rare" and having a prevalence of one in a million causes zero interest on the part of scientific laboratories to investigate it. In this way, the relatives are forced to cover the expenses with the help of local administrations for the investigation.

Those most likely to suffer from PN are adolescents and children, although it is known that it can strike at any age, and life expectancy is less than 10 years in children and 30 in young people.

Forecast

The development of this disease is characterized by the gradual deterioration of the vital functions of the organism. The disease discovered by doctors Niemann and Pick is degenerative and, therefore, fatal in 100% of cases.

Treatment

It is recommended for patients to have a diet low in cholesterol, but neither this nor “lipid-lowering drugs” stop the progress of the disease. But many symptoms produced by type C (cataplexy and seizures) have been able to be stopped with medication.

An effective treatment has not yet been found to completely cure this disease. However, at present, attempts are being made to alleviate the complications that appear during the course of the disease through:

• Physical and therapeutic activities.
• Improved nutrition.
• Treatment against the epileptic crises caused by the cholesterol cluster in the nervous system.
• Treatment of miglustat in order to stop the disease.

Main lipidoses

• Disease of Gaucher
• Niemann-Pick disease
• Fabry disease
• Wolman's disease
• Xantomatosis cerebrotendinosa
• Sitosterolemia
• Refsum disease
• Metachromatic leukodystrophy