Of the Niemann-Pick disease is also as Niemann-Pick disease known. The hereditary disease is one of the lysosomal storage diseases.
What is Niemann-Pick Disease?
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Of the Niemann-Pick disease is a disease from the group of sphingolipidoses. These are metabolic diseases that mostly manifest themselves in the central nervous system. Within the sphingolipidoses, the disease belongs to the lysosomal storage diseases. These are characterized by malfunctions in the lysosomes.
In English-speaking countries, the term Lysosomal Storage Diseases (LSDs) are used. In Niemann-Pick's disease, sphingomyelin is deposited in the liver, bone marrow, spleen and brain. The disease was named after its discoverers Albert Niemann and Ludwig Pick. It was first described in 1914. Niemann-Pick disease occurs rather rarely.
Around one newborn in 8,000 births will develop a lysosomal storage disease. But that doesn't just include that Niemann-Pick disease, but also diseases like Hunter syndrome or Sanfilippo syndrome.
causes
Niemann-Pick disease is inherited as an autosomal recessive trait. In autosomal recessive inheritance, the defective allele is on a homologous chromosome or an autosome. Only homozygous carriers of the trait become ill. This means that the genetic material of a cell must have two identical copies of the defective gene on both chromosomes for the disease to break out.
The Niemann-Pick syndrome is based on a genetic enzyme defect. The enzyme sphingomyelinase is affected. The sphingomyelinase is responsible for the cleavage of sphingomyelin. The enzyme defect leads to increased storage of sphingomyelins in the lysosomes of the spleen, bone marrow, brain and liver. Lysosomes are cell organelles that contain digestive enzymes.
They digest foreign material such as pathogens or cell debris. They also play an important role in programmed cell death (apoptosis). In animal experiments it could be shown that the expression of the myelin gene regulatory factor (MRF) is significantly reduced by the mutation in the NPC-1 gene. The protein MRF is a so-called transcription factor. In gene coding, it plays a role in the formation and protection of myelin sheaths.
Myelin sheaths cover the nerve fibers and ensure that stimuli are passed on quickly. Presumably, the neurological deficits that occur in Niemann-Pick's disease are based on an incorrect differentiation of oligodendrocytes. These cells belong to the glial cells. Their cell processes cover the cell processes of the nerve fibers as myelin sheaths. Thus, the faulty differentiation of the oligodendrocytes leads to a lack of or insufficient myelination.
In the case of Niemann-Pick type C disease, the cholesterol metabolism is also impaired. In addition to the sphingomyelins, cholesterol and other metabolic products also accumulate here in the body's cells.
Symptoms, ailments & signs
Niemann-Pick's disease can be divided into three forms:
- Type IA is also known as the acute infantile neuropathic form. The disease begins at the age of three months and manifests itself as a poor drinking and developmental disorders of individual tissues and organs.
The main symptom is swelling of the liver (hepatomegaly). This can also occur in combination with a swelling of the spleen (splenomegaly). In addition, the lymph nodes can be felt and brown discoloration of the skin occurs. Neurological degradation begins in the second year of life. Affected young children become deaf, blind and lose social contact.
The prognosis is poor, which means that all children with Niemann-Pick type IA disease will die within two years. This form is the most common variant of the disease.
- TYPE IS is also known as the chronic visceral form. It is a mild course with liver swelling and lung infiltrates. There is no involvement of the central nervous system. The life expectancy of patients is only slightly restricted.
- In type C of Niemann-Pick's disease, neonatal jaundice occurs. The skin and sclera of the affected newborns are colored yellow by deposits of the dye bilirubin. Supranuclear palsy is also typical of this variant of the disease. This leads to progressive paralysis of the eye muscles with double vision or disorders of balance.
Cerebellar ataxia with impaired movement coordination can also be observed. In the course of the disease, patients often develop swallowing disorders. This can cause aspiration pneumonia. The onset of the disease in type C is very variable. The first symptoms can appear in infants, children or even in adolescence or adulthood.
Diagnosis & course of disease
If the risk of the disease is known, prenatal diagnosis is possible. If Niemann-Pick's disease is suspected, white blood cells are taken from the bone marrow. These appear vacuolated. This means that the leukocytes have cavities. There are also vacuolated foam cells.
This phenomenon is known as "sea blue histiocytosis". The lack of activity of the enzyme sphingomyelinase can be detected in the cultures of leukocytes and fibroblasts. Every second child with Niemann-Pick's disease shows a red macular mark during an ocular fundus.
Complications
Depending on the type, Niemann-Pick disease is associated with a number of complications. With TYPE IS, liver swelling and lung infiltrates, i.e. accumulations of foreign bodies in the lungs, can occur. The life expectancy of those affected is slightly restricted and the quality of life is sometimes severely impaired. With type C, the first symptoms can appear in infancy.
This can lead to severe developmental disorders, which are often associated with cerebellar ataxia with disorders of movement coordination. In the course of the disease, swallowing disorders sometimes occur, which lead to aspiration pneumonia and other complications. Those affected sometimes show symptoms of shortness of breath, which is associated with coughing with sputum, increased body temperature and a blue discoloration of the skin and mucous membranes.
In turn, such cyanosis is fraught with serious complications. In TYPE IA, there is early drinking weakness and developmental disorders of organs and tissues. The swelling of the liver is usually associated with a swelling of the spleen, which causes severe physical impairment in those affected.
Infections occur more frequently, the gastrointestinal tract becomes inflamed and the body's own functions rapidly decline. The affected small children usually become deaf and blind within two years before they finally die from the severe complications of Niemann-Pick disease.
When should you go to the doctor?
Niemann-Pick disease is an inherited disease that takes a progressive course. Parents who find that their child has recurrent jaundice and muscle discomfort should contact the pediatrician. If there are motor development delays or psychological behavior disorders, the suspicion of a serious illness that needs to be diagnosed and treated is obvious.
Parents or guardians should visit a specialized center for rare metabolic diseases. Children with Niemann-Pick syndrome require ongoing medical treatment due to increasing physical and mental problems.
Unusual symptoms or a sudden increase in typical symptoms must be reported to the responsible doctor. The same applies if the child can no longer tolerate the prescribed medication or shows other deviations from normal behavior. Routine treatments such as stopping medication and physical exams may be performed by your GP.
Most people with Niemann-Pick disease have to be treated by metabolic diseases specialists. The individual symptoms are treated by neurologists, orthopedists and speech therapists. In addition, physiotherapists and occupational therapists are involved in the treatment. A therapist can also be called in for psychological complaints such as depression or delusions. Due to the large number of possible symptoms, Niemann-Pick disease usually has to be treated by a team of doctors.
Therapy & Treatment
A causal therapy is currently not known. However, there is evidence that special cyclodextrins can alleviate the symptoms of the disease. Cyclodextrins are cyclic oligosaccharides that are often used as solvents in drug production. Niemann-Pick type C disease is treated with miglustat.
Miglustat is a drug that is only approved in the European Union for the treatment of Niemann-Pick disease and for the treatment of Gaucher's disease type 1. The drug is an iminosugar and an n-butyl derivative of moranoline.
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➔ Medicines for painOutlook & forecast
The prognosis for Niemann-Pick disease is poor. The disease is a genetic defect. Current legislation prohibits scientists from interfering with or modifying human genetics. Although the disease can be diagnosed before birth, no cure is possible based on legal requirements.
To this day, doctors and medical professionals have been concentrating on developing adequate medical care after the person is born. Treatment currently consists of initiating drug therapy in order to support the patient's metabolism as best as possible. As a result, optimizations are already possible in the patient's development process, which contribute to improving the overall situation.
Without treatment, the affected person's quality of life is greatly reduced. In addition, life-threatening conditions can develop, as the disease is accompanied by swelling of internal organs and shortness of breath. The risk of an emergency situation is significantly increased without treatment. Long-term therapy is therefore indicated regardless of the intensity of the individual symptoms. The patients need daily care and support in coping with everyday life. Depending on the type of disease present, if the disease progresses poorly, the patient may die prematurely within the first few years of life.
prevention
Niemann-Pick's disease is inherited as an autosomal recessive trait. There is currently no effective prevention.
Aftercare
In most cases, the affected person has only a few and only limited follow-up measures available for Niemann-Pick disease. For this reason, the patient must consult a doctor at the first signs and symptoms so that there are no other complications or complaints. The earlier a doctor is contacted, the better the further course of the disease, so that a doctor should be consulted as soon as the first symptoms or signs appear.
If the patient wishes to have children, genetic testing and counseling should definitely be carried out in order to prevent the recurrence of Niemann-Pick disease. Most of the patients are usually dependent on the intake of various drugs.
The person affected should always pay attention to the correct dosage and also to regular intake in order to permanently alleviate the symptoms. If anything is unclear or if you have any questions, a doctor should always be consulted first. Likewise, many of the patients are dependent on the help and support of their own families in their everyday lives. Above all, depression and other psychological complaints can be alleviated.
You can do that yourself
The possibilities of self-help are extremely limited with Niemann-Pick disease. Type IA in particular does not offer sufficient opportunities to improve the situation. The life expectancy of the sick child is very low despite all efforts.
In everyday life, the focus should therefore be on making time together as pleasant as possible. Enjoying leisure time is important in order to build closeness, solidarity and stability. The disease is an enormous challenge for both patients and relatives. Building up mental powers is particularly important when coping with adversity. For this reason, psychological support is essential for everyone involved.
For many, it is also a help if there is the possibility of an exchange with other affected persons. It can therefore be beneficial to contact established self-help groups. In joint discussions, an exchange takes place on the basis of mutual understanding. Communication can help with processing. It also gives tips for coping well.
Mental techniques and relaxation exercises promote the reduction of stressors. Since situations of excessive stress and thus vegetative problems often arise, the training units can help to reduce stress. Dealing with the overall situation should thereby be improved.
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