Synthegue's Syndrome

The syndrome of Zweveger is a fairly severe hereditary disease.

Among doctors is also called cerebrohepatorenal syndrome. The main cause of the disease is the lack of peroxisomes in the tissues of the body.

Causes of the syndrome

Cases of the syndrome of Zeroveger account for 80% of all those who suffer from peroxisome biogenesis. This disease is considered fatal. It is transmitted by an autosomal recessive type. It is only hereditary. Therefore, the main cause of the syndrome is a change in the genetic code, namely, mutations in the following genes of peroxins 1,2,3,5,6 and 12.

[1], [2], [3], [4], [5], [6], [7], [8]

Pathogenesis

The syndrome of Zweveger is a rather rare disease. It is a prototype of peroxisome diseases that manifest themselves with the same or similar symptoms and disorders in the biochemical plan. Children who suffer from the syndrome of Zweveger, notice the dysmorphia of the facial bones: a strong bulge appears in the frontal region, and the anterior fontanelle differs too large in size. The ears often develop abnormally, and the occiput is too flattened. A lot of skin folds develop on the neck, the sky is a Gothic, strongly noticeable areflexion and hypotonia of the muscles.

[9], [10], [11], [12], [13], [14], [15], [16], [17], [18],

Symptoms of the syndrome

The main pathognomonic symptoms of this disease can be identified as follows:

1. Muscular hypotension manifests itself in a rather severe form.
2. Infants are too sluggish sucking on the mother's breast or nipples.
3. Reflexes of the tendon are too low.
4. Nystagmus and cramps.
5. Contracture.
6. Hepatomegaly.
7. Sometimes jaundice may appear from the first days of life.
8. The number of enzymes peroxisomes in the liver increases.
9. Cholestasis.
10. Steatorrhea.
11. Fibrosis of the liver.
12. Deafness sensorial.
13. A variety of visual disturbances (opacities, cataracts, glaucoma, atrophy of nerves).
14. In rare cases, cysts in the liver and kidneys may appear.
15. Sometimes there is atrophy of the adrenal glands.
16. All patients suffer from delayed growth and developmental delay.
17. Insufficient psychomotor development.
18. Anomaly of the development of the skeleton (epiphyseal dysplasia in the region of the knee cups and femur).

First signs

The disease begins to develop in the neonatal period. The first signs of the syndrome of Zweveger appear even from birth. First, the weight of the newborn patient for this serious illness does not exceed 2500 grams. The structure of the face is quite typical for the disease and differs in dysmorphism. All patients suffer from brain development disorders. Deficiency of the heart and external genital organs may manifest.

[19], [20]

Complications and consequences

Unfortunately, the consequences of the Zellweger syndrome are disappointing. First, this disease is the cause of many other serious illnesses. Almost from the very first days of life, infants suffer from jaundice, they show different vices and anomalies. Very often doctors notice patients hydrocephalus, lisencephaly and polymicrogyria. At the moment, the consequences of the Zellweger syndrome are fatal.

[21], [22]

Complications

The syndrome of Zweveger got its name after the name of its discoverer, an American pediatrician. The disease has a lethal outcome at a very early age. The most complex complications of the Zellweger syndrome include a delay in psychosomatic development, dysplasia, muscle hypotension, glaucoma and cataract development, dolichocephaly, various kidney and liver lesions, heart, lung and genital anomalies. All these anomalies are incompatible with life.

[23], [24], [25], [26], [27]

Diagnostics of the syndrome

Assumption on the syndrome of Zweveger can be made after a routine physical examination by a doctor. But a serious diagnosis can be confirmed only after a full biochemical analysis. It should be understood that peroxisome biogenesis is impaired in patients with the Zweveger syndrome due to mutations in one of the thirteen known genes (PEX). They are the ones that code for peroxisomes. If at least one of these genes shows a mutation, then this leads to an anomaly of biogenesis by peroxisomes.

[28], [29], [30], [31], [32]

Analyzes

As already mentioned above, in order to confirm a terrible disease it is necessary to conduct a biochemical analysis. If, in analyzing the level of fatty acids with a rather long chain, there are abnormalities in the metabolism of the peroxisomal fatty acid and, at the same time, there is an increased concentration in the plasma, one can speak of the development of the Zellweger syndrome. In this case, the number of plasmagens (C18 and C16) in erythrocyte membranes is low, and pinecolinic acid is increased. To make sure of the diagnosis, sometimes the doctor can recommend going through another analysis: sequences of thirteen PEX genes.

[33]

Instrumental diagnostics

To detect perivilvial poly-microorganism, as well as some other malformations of the brain in the syndrome of Zeroveger, MRI (magnetic resonance imaging) is sometimes used. This tomographic method makes it possible to study the internal organs and tissues without problems with the help of nuclear magnetic resonance. Thanks to this method, it is possible to see which disorders and anomalies were developed in the patient.

Differential diagnosis

Among the most popular methods of differential diagnosis is Usher's syndrome 1 and 2, some basic violations of peroxisome biogenesis, the search for defects of one of the enzymes in the process of beta-oxidation of fatty acid in peroxisomes.

During pregnancy, if the doctor suspects the possibility of developing a fetal syndrome, you can conduct a prenatal study of amniocytes, as well as a special analysis of the chorionic villus biopsy for the existence of fatty acids with too long chains. The synthesis of plasmogenogen is also analyzed. If both analyzes show allelic genes that can cause the syndrome, it is worthwhile to do DNA research with prenatal diagnosis, as well as gene diagnosis (pre-implantation).

Since the Zellweger syndrome is an autosomal recessive disease, it can be diagnosed by genetic counseling.

[34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44],

Treatment of the syndrome

Unfortunately, there are no medications for the Zellweger syndrome today. You can use some medications to control cramps. As a rule, conventional antiepileptic agents are suitable for this purpose:

• Actinerval. The main active ingredient is carbamazepine. It is a popular antiepileptic remedy. It is taken orally by eating with a small amount of liquid. Dosage for children, approximately, this: up to 20 mg per 1 kg per day.
• Benzonal. The active ingredient is benzobarbital. Children are prescribed tablets of 0.05 grams. Take after meals, washing down with plenty of water. The dose depends on the frequency of seizures and their strength, and therefore is individual.

To alleviate the effects of hepatic hepatic coagulopathy, one can prescribe vitamin K, and in the development of cholestasis, in some cases, fat-soluble vitamins can be used. 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 phytic acid (cow's milk). Infants with severe development of hepatopathy must be given cholic, bile and chenodeoxycholic acid. This will help relieve the pain. Since docosahexaenoic acid is not synthesized by the body in patients with the Zweveger syndrome, it must also be delivered by the unit route.

Prevention

Preventive maintenance of the syndrome is based, above all, on the proper genetic counseling of a young family, as well as on the conduct of various methods of prenatal diagnosis. If people with peroxisome diseases are detected in a timely manner, this will allow to conduct all the necessary medical methods that will help prevent the development of disorders in the central nervous system and other body systems.

[45], [46], [47], [48], [49], [50], [51], [52], [53], [54]

Forecast

As a rule, patients with the syndrome of Tseveveger do not live very long. Death usually occurs six months after birth. In some rare cases, infants can survive up to one year.

[55], [56], [57], [58]