Zellweger's syndrome

Zellweger syndrome is a rather severe hereditary disease.

Among doctors it is also called cerebrohepatorenal syndrome. The main cause of the disease is considered to be a lack of peroxisomes in the body's tissues.

Causes Zellweger's syndrome

Cases of Zellweger syndrome account for 80% of all those who suffer from peroxisomal biogenesis disorder. This disease is considered fatal. It is transmitted in an autosomal recessive manner. It is transmitted only hereditarily. Therefore, the main cause of Zellweger syndrome is considered to be a change in the genetic code, namely, mutations in the following genes of peroxins 1,2,3,5,6 and 12.

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Pathogenesis

Zellweger syndrome is a rare disorder. It is a prototype of peroxisomal diseases, which manifest with the same or similar symptoms and biochemical abnormalities. Children with Zellweger syndrome have noticeable dysmorphism of the facial bones: a strong bulge appears in the frontal area, and the anterior fontanelle is too large. The auricles often develop abnormally, and the back of the head is too flat. Many folds of skin develop on the neck, the palate is gothic, areflexia and muscle hypotonia are very noticeable.

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Symptoms Zellweger's syndrome

The main pathognomonic symptoms of this disease include the following:

1. Muscle hypotonia manifests itself in a rather severe form.
2. Babies suck too weakly on their mother's breast or nipple.
3. Tendon reflexes are too low.
4. Nystagmus and convulsions.
5. Contracture.
6. Hepatomegaly.
7. Sometimes jaundice may appear from the very first days of life.
8. The amount of peroxisomal enzymes in the liver increases.
9. Cholestasis.
10. Steatorrhea.
11. Liver fibrosis.
12. Sensorineural deafness.
13. Various visual impairments (opacities, cataracts, glaucoma, nerve atrophy).
14. In rare cases, cysts may appear in the liver and kidneys.
15. Sometimes there is atrophy of the adrenal glands.
16. All patients suffer from delayed growth and development.
17. Insufficient psychomotor development.
18. Anomaly of skeletal development (epiphyseal dysplasia in the area of the kneecaps and femur).

First signs

The disease begins to develop in the neonatal period. The first signs of Zellweger syndrome appear from birth. Firstly, the weight of a newborn, sick with this serious disease, does not exceed 2500 grams. The structure of the face is quite typical for the disease and is characterized by dysmorphism. All patients suffer from impaired brain development. Heart defects and external genitalia may appear.

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Complications and consequences

Unfortunately, the consequences of Zellweger syndrome are disappointing. Firstly, this disease is the cause of many other rather serious diseases. Almost from the first days of life, infants suffer from jaundice, they have various defects and anomalies. Very often, doctors notice hydrocephalus, lissencephaly and polymicrogyria in patients. At the moment, the consequences of Zellweger syndrome are fatal.

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Complications

Zellweger syndrome is named after its discoverer, an American pediatrician. The disease is fatal at a very early age. The most severe complications of Zellweger syndrome include delayed psychosomatic development, growth disorders, muscle hypotonia, development of glaucoma and cataracts, dolichocephaly, various kidney and liver lesions, abnormalities of the heart, lungs and genitals. All of these abnormalities are incompatible with life.

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Diagnostics Zellweger's syndrome

A suspicion of Zellweger syndrome can be made after a routine physical examination by a doctor. But a serious diagnosis can only be confirmed after a full biochemical analysis. It is worth understanding that peroxisome biogenesis is disrupted in patients with Zellweger syndrome due to mutations in one of the thirteen known genes (PEX). They are the ones that encode peroxisomes. If at least one of these genes has a mutation, this leads to an anomaly in peroxisome biogenesis.

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Tests

As mentioned above, to confirm the terrible disease, it is necessary to conduct a biochemical analysis. If, when analyzing the level of fatty acids with a fairly long chain, disturbances in the metabolism of peroxisomal fatty acid are detected and, at the same time, there is an increased concentration of it in the plasma, we can talk about the development of Zellweger syndrome. In this case, the amount of plasmagens (C18 and C16) in the erythrocyte membranes is reduced, and pinecolic acid is increased. To confirm the diagnosis, the doctor may sometimes recommend another analysis: the sequence of thirteen PEX genes.

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Instrumental diagnostics

To detect perisylvian polymicrogyria, as well as some other malformations of the brain in Zellweger syndrome, MRI (magnetic resonance imaging) is sometimes used. This tomographic method allows for the easy examination of internal organs and tissues using nuclear magnetic resonance. Thanks to this method, it is possible to see what kind of disorders and anomalies were developed in the patient.

Differential diagnosis

Among the most popular methods of differential diagnostics are Usher syndrome 1 and 2, some major disorders of peroxisome biogenesis, and the search for defects in one of the enzymes in the process of beta-oxidation of fatty acids in peroxisomes.

During pregnancy, if the doctor suspects the fetus may develop Zellweger syndrome, a prenatal study of amniocytes can be performed, as well as a special analysis of the chorionic villus biopsy for the presence of fatty acids with too long chains. A plasmalogen synthesis analysis is also performed. If both analyses show allelic genes that can cause the syndrome, it is worth conducting a DNA study using prenatal diagnostics, as well as gene diagnostics (preimplantation).

Since Zellweger syndrome is an autosomal recessive disorder, it can be diagnosed through genetic counseling.

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Treatment Zellweger's syndrome

Unfortunately, there is currently no cure for Zellweger syndrome. Some medications can be used to control seizures. Common antiepileptic drugs are usually suitable for this purpose:

• Actinevral. The main active ingredient is carbamazepine. It is a popular antiepileptic drug. It is taken orally during meals with a small amount of liquid. The dosage for children is approximately as follows: up to 20 mg per 1 kg per day.
• Benzonal. The active ingredient is benzobarbital. Children are prescribed 0.05 gram tablets. Take after meals with plenty of water. The dose depends on the frequency of seizures and their strength, so it is individual.

To alleviate the consequences of hepatic hepatic coagulopathy, you can give vitamin K, and in the development of cholestasis in some cases, you can use fat-soluble vitamins. Sometimes it is necessary to install a special gastrostomy tube to replace the missing calories. Try to limit the consumption of those products that contain a large amount of phytanic acid (cow's milk). Infants with severe hepatopathy should be given cholic, bile and chenodeoxycholic acids. This will help relieve pain. Since docosahexaenoic acid is not synthesized by the body in patients with Zellweger syndrome, it must also be delivered artificially.

Prevention

Prevention of Zellweger syndrome is based primarily on proper genetic counseling of a young family, as well as on various methods of prenatal diagnostics. If people with peroxisomal diseases are identified in a timely manner, this will allow all necessary treatment methods to be carried out, which will help prevent the development of disorders in the central nervous system and other body systems.

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Forecast

As a rule, people with Zellweger syndrome do not live very long. Death usually occurs within six months after birth. In some rare cases, infants can live up to one year.

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