Nyman-Pick's disease: what is it, symptoms and treatment

Niman-Pick's disease (sphingomyelinosis) is a hereditary disease associated with excessive accumulation of fats in various organs and tissues, primarily in the brain, liver, lymph nodes, spleen, bone marrow. Has several clinical options, each with a different prognosis. Specific treatment is currently not available. From this article you can learn about the cause, symptoms and possibilities of treating Nyman-Pick's disease.

Nyman-Pick's disease refers to lysosomal accumulation diseases. This is when, as a result of insufficient activity of an enzyme, intermediate metabolic products accumulate in the cells of the body, which normally undergo further cleavage.

Causes of Niman-Pick disease

At the heart of the disease is the genetic defect of the 11th chromosome (types A and B), the 14th and 18th chromosomes (type C). As a result of the presence of a disorder in the structure of the gene, a decrease in the activity of the sphingomyelinase enzyme is observed in humans, which splits sphingomyelin. Sphingomyelin is a kind of fat. Such a biochemical disorder leads to an excessive accumulation of sphingomyelin and cholesterol in the cells of the reticuloendothelial system: tissue macrophages. As a result, the metabolism is disrupted.

Tissue macrophages are scattered throughout the body, but most of all in the spleen, liver, bone marrow, lymph nodes, central nervous system.

The disease is autosomal recessive, that is, it is not related to sex, both men and women can be ill. With the coincidence of two pathological genes (from the father and from the mother), the illness proceeds most severely.

Symptoms

There are several clinical variants of Niman-Pick disease. The division into variants is due to the peculiarities of the current and biochemical changes.

In total, 4 types of the disease were studied:

• Type A - a classical form of the disease (infantile, acute neuropathic);
• type B - visceral form (chronic, without involvement of the nervous system);
• type C - juvenile form (subacute, chronic neuropathic);
• type D - a form from Novaya Scotia (after the name of the province in Canada, in the inhabitants of which this form is found). Recently, this type has been combined with type C.

Type A

This is the most unfavorable form of life expectancy. It manifests itself several weeks after birth (at birth, the children look healthy). The child's appetite worsens, he begins to lose weight and lag behind in growth. Periodic vomiting and diarrhea are possible. Gradually, the abdomen grows because of the liver and spleen (the liver increases earlier than the spleen), ascites develops. The limbs look thin and very thin compared to an enlarged abdomen.

The baby's skin becomes dry, loses its elasticity, acquires a yellowish color, in places yellowish-gray or yellow-brown spots are determined. All groups of lymph nodes increase, which can be determined by palpation.

When examining the fundus, a specific symptom of the "cherry stone" is determined - a dark red color speck on the retina. Perhaps the opacity of the cornea and the appearance of a brown color of the lens.

The defeat of the nervous system is first in the lag in the neuropsychological development of peers: the kids do not keep their head, do not turn over from their stomachs to their backs, they do not follow the toy. Increases muscle tone in the arms and legs, develops muscle weakness. Tendon reflexes also increase. Gradually, hearing is lost, vision is reduced, there may be epileptic seizures. At the height of the disease, the child is languid and apathetic, reacts weakly to events around him, almost always resides with an open mouth, which causes salivation.

There are periods of sudden temperature increase: hyperthermal crises.

Gradually, exhaustion develops, and patients with this form of disease die at the age of 2-4 years.

Type B

This form of the disease has a favorable course. In this case, the nervous system is not affected, the accumulation of sphingomyelin and cholesterol occurs only in internal organs. Why the nervous system remains untouched - still remains a mystery for doctors.

At first the spleen is enlarged, usually it takes place 2-6 years. Later, the liver is enlarged. The defeat of the liver leads to increased bleeding due to a disorder in the blood coagulation system. Anemia often develops. Disturb pain in the abdomen, periodic stool disorders, occasionally nausea and vomiting. The abdomen increases in size, but not as much as in type A.

In connection with the accumulation of fats in the lung tissue, infiltrates are formed. This causes frequent colds in these children.

This form is characterized by a prolonged chronic course. Lifespan is significantly longer than in type A, patients survive to adulthood.

Type C

The biochemical defect with this form is not exactly clear. There is a violation of sphingomyelin transport. There is an inordinate accumulation of sphingomyelin and a significant accumulation of cholesterol in the brain, spleen, and liver.

The disease first manifests itself in the interval from 2 to 20 years. The enlargement of the liver and spleen is insignificant in comparison with types A and B. The icteric color of the skin is characteristic. On the fundus there is a symptom of the "cherry stone", pigmentary degeneration of the retina.

Neurological disorders begin with a decrease in muscle tone, which then, on the contrary, increases. Gradually formed spastic paresis: muscle weakness with a simultaneous increase in muscle tone. The joint activity of eyeballs is disrupted, coordinated eye movements become impossible, especially when looking upwards (the so-called vertical ophthalmoparesis).

There is a development of a lack of coordination, in connection with which the gait changes. Jitter and involuntary movements in the limbs are attached. Characteristic violent twisting movements in the head and trunk (torsion dystonia). There are epileptic seizures. Violated swallowing and speech. Mental disorders gradually progress, children lose the ability to learn, eventually dementia develops (dementia). Violated control of the function of the pelvic organs. A rather specific symptom for this form of Nyman-Pick disease is described: it is a sudden loss of muscle tone in the legs, jaw and neck with laughter or other strong emotions. The disease gradually progresses.

After the appearance of a detailed clinical picture of the disease, the days of such patients are numbered.

Type D

Described among the inhabitants of the province of Canada: Nova Scotia (Scotia). A clear biochemical defect is not revealed, but the disease develops as a result of a small accumulation of sphingomyelin and a significant - cholesterol. In its clinical manifestations practically does not differ from type C, therefore some researchers prefer not to separate it into a separate form.

Diagnostics

To confirm the diagnosis, the activity of sphingomyelinase in the culture of skin fibroblasts and leukocytes (for type A and B) is determined, the accumulation unesterified cholesterol in the culture of skin fibroblasts (for type C), search for genetic defects in 11, 14, 18 chromosomes.

Puncture of the bone marrow in such patients reveals the specific "foamy" cells of Niemann-Pick (they look like that because of the accumulation of fats).

Treatment

The disease is incurable. In general, symptomatic treatment is carried out to alleviate the suffering of the patient.

Among the symptomatic agents used:

• anticonvulsants (Depakin and other Valproats);
• drugs to correct drooling (dripping Atropine in the mouth, injecting botulinum toxin into the salivary glands, using hyoscine patches);
• with mental disorders - antidepressants (selective inhibitors of serotonin reuptake - Prozac, Serlift, Zoloft) with depression and Valproate in psychoses;
• antidiarrhoeals: Loperamide (Imodium), diet therapy;
• when developing infectious complications from the respiratory tract, use antibiotics, bronchodilators (Berodual), physiotherapy procedures;
• with dystonia and trembling: anticholinergic drugs (Cyclodol, Parkopan, Biperiden, Akineton).

In recent years, to stop the accumulation of sphingomyelin in the cells began to use Miglustat. It blocks the enzyme responsible for synthesizing glycosphingolipids (precursors of sphingomyelin). Apply in dosage from 100 mg 1-2 times a day to 200 mg 3 times a day (depending on the age and body area of ​​the patient). Miglustat prevents the destruction of nerve cells and, thus, slows the development of neurological symptoms, leads to an increase in life expectancy. Visible positive result from the use of the drug develops after 6 months-1 year of continuous admission.

Thus, Nyman-Pick's disease is a rather severe hereditary disease of sphingomyelin accumulation in cells of the body, which leads to damage to the liver, brain, lymph nodes, lungs. The disease has a steadily progressing character. In some cases, patients quickly die, other types are more benign. Clear and effective treatment is currently not developed, but successful steps in this direction have already been made.