Zellweger syndrome is the medical term for a genetic and fatal metabolic disease. This is manifested by and can be characterized by the absence of peroxisomes. The syndrome is congenital due to a gene mutation and can be inherited in families.
What is Zellweger syndrome?
Zellweger syndrome is a relatively rare inherited disorder. It is manifested by the absence of peroxisomes (organelles in eukaryotic cells, they are often called microbodies) and is diagnosed in about one in 100,000 babies on average. Since 1964, more than 100 cases have been documented, including siblings. In 1964, the disease was described by the American physician Hans Ulrich Zellweger, after whom the syndrome was consequently named. He had diagnosed the genetic defect in twins.
Causes
The syndrome is characterized primarily by the absence of peroxisomes or by a disrupted peroxisomal gene structure (called biogenesis). This is due to congenital and often inherited gene mutations. As a rule, the genes that are significantly responsible for the formation of peroxisomes are affected. Various biochemical reactions take place in the peroxisomes, which are directly or indirectly associated with the degradation and formation of various endogenous substances – such as fatty and bile acids. However, it is still unclear what role peroxisomes play in the body as an essential substance and what exactly causes their failure or disruption in Zellweger syndrome. The gene disruption or absence of peroxisomes is often accompanied by loss of certain liver, kidney and other organ functions in Zellweger syndrome. In addition, inactive peroxisomal enzymes may also occur, which can affect various metabolic functions of the body in different ways, depending on the severity. Accordingly, the “cause” at hand may be manifested by different symptoms, which in turn cause other symptoms. In addition, Zellweger syndrome is now researched in two types, the actual Zellweger syndrome and the so-called pseudo Zellweger syndrome. The latter is referred to when the peroxisomal enzymes are inactive.
Symptoms, complaints, and signs
Zellweger syndrome is manifested by a variety of features on the entire body of the newborn. For example, there is often a vertical maldevelopment or overdevelopment of the head (called long skull), a poorly defined nasal bridge, a flat and rectangular-looking face, a relatively large distance between the eyes (called hypertelorism), opacity of the cornea and lens. Furthermore, cysts in the brain, underdevelopment of the lungs, and severe cognitive disabilities, severe psychomotor developmental delays, and defective development of the external sex organs in girls. In addition, Zellweger syndrome is not infrequently manifested by quite shrill-sounding crying, by lack of reflexes, by epilepsy, by difficult breathing, and by short stature. In addition, affected children are usually born prematurely and therefore far before the expected date of birth. Nevertheless, the lists of symptoms, complaints and signs associated with Zellweger syndrome do not end there. Because the symptoms, signs and peculiarities can occur in a wide variety of manifestations and combinations. For this reason, the syndrome is not always correctly diagnosed right away, even today.
Diagnosis and course of the disease
Zellweger syndrome is diagnosed in most babies by the clearly visible signs on the face or by cysts in the brain. However, diagnosis of the syndrome can also be made by detecting changes in the body’s fatty acids. In addition, in a culture of fibroblasts and hepatocytes, the absence of peroxisomes can be determined and thus also detected. Finally, however, the diagnosis should be confirmed by identification of the genetic mutation due to its numerous symptoms, signs and complaints, which often occur in very different combinations with each other. The syndrome cannot always be diagnosed directly and can quickly be confused with other hereditary diseases, disorders and genetic mutations due to its large number of different symptoms, signs and complaints. Therefore, even today it is possible that the syndrome is not recognized as such at all or only later.In addition, the course of the disease is always different, depending on the manifestation of the syndrome. Here, it depends above all on which body parts, organs and bodily functions are affected and to what extent. Even today, however, children suffering from the syndrome are not considered capable of survival and die in the first few months after birth.
Complications
Zellweger syndrome is a serious disorder that can cause various complications as it progresses. Characteristic disorders such as corneal and lens opacification result in visual disturbances and may lead to partial or complete blindness in the later stages. Underdeveloped lungs are associated with decreased exercise capacity. In addition, respiratory problems and an undersupply of oxygen to the brain may occur. The typical cognitive disabilities and psychomotor developmental delays often have psychological effects as well. This affects not only the sufferers, but also their relatives, who usually suffer greatly from the stress and poor general condition of the sufferer. Other complications that can occur are epilepsy and neurological disorders, both of which are associated with the risk of accidents. Zellweger syndrome almost always takes a fatal course, as no effective treatment options exist to date. Although the individual symptoms and complaints can be treated, this is also associated with risks. Because affected individuals are almost always infants and young children, even marginal errors in surgical procedures or medication can have serious health consequences.
When should you see a doctor?
Because the disorder is hereditary, if there is a family history of the disorder, contact should be made with a physician even before planning for offspring. Although the syndrome is very rare, it can be inherited by offspring. If a diagnosis has already been made within the family, a doctor should be consulted at an early stage. If parents have no knowledge of a genetic disposition within the family, visual abnormalities in the child often become apparent immediately after birth. In addition, there is often a premature birth. Normally, the birth is attended by a team of obstetricians or a physician. These take over the first examinations of the baby in a routine procedure. The visual abnormalities in the area of the face are therefore noticed by them immediately after the birth. Further examinations are initiated so that a clarification of the cause can be achieved. If in rare cases no diagnosis occurs in infancy, parents should consult a doctor as soon as their offspring shows delays in development. In case of seizures, behavioral disorders of the child or visual abnormalities in the growth process, a visit to the doctor is necessary. A clouding of the cornea, disturbances of the respiratory activity as well as peculiarities of the memory performance are further signs of a health impairment. Medical examinations are necessary so that the first treatment steps can be initiated at an early stage.
Treatment and therapy
Despite the most modern research, a cure for the syndrome is not possible to date, as there are no treatment or therapy options available. Only certain complaints and symptoms can be treated, so that these can possibly be reduced. However, this is also not the case across the board. Children with Zellweger syndrome are not considered viable in the long term, as the syndrome is always lethal (fatal) according to current findings. All children known to date died within the first few months of life.
Prevention
Because Zellweger syndrome is a congenital genetic mutation, it cannot be prevented. However, certain symptoms and signs can now be diagnosed in the womb under certain circumstances using various examination procedures. This is often useful or the case, for example, when an affected couple has already given birth to an infant with the genetic disorder. However, even today, not all combinations of the gene disorder can be diagnosed in advance without error.
Follow-up
In most cases, the affected person has very few and also very limited measures of direct aftercare available to him or her in Zellweger syndrome.Therefore, in the case of this disease, the affected person should see a doctor at an early stage and have treatment initiated so that further complaints or complications do not arise. An early diagnosis usually has a very positive effect on the further course of the disease. Since this is a genetic disease, it cannot be cured in most cases. Therefore, if the affected person wishes to have children, a genetic examination is advisable in the first place to determine the possibility of a recurrence of Zellweger syndrome in the descendants. Furthermore, in many cases, care and support from one’s family is very important. This can also prevent the development of depression and other psychological upsets. Often the parents are dependent on psychological treatment, because the children usually die quickly. Contact with others affected by Zellweger’s syndrome can be very useful, as it leads to an exchange of information.
What you can do yourself
Zellweger syndrome is usually fatal for the affected child. The most important self-help measure is to deal openly with the disease. It is important to take advantage of the time available with the child. In most cases, it is possible for close relatives to spend the time after the birth in the hospital. Special mother-child rooms are provided in most specialized hospitals and are a good way for parents to spend time with the sick child. Parents should seek trauma therapy early on or seek out a support group in consultation with the doctor. In addition, it is important to make preparations for the death of the child and, for example, to organize a baptism or the funeral. The doctor in charge will help with this. Zellweger syndrome is an extremely rare condition, which is why coming to terms with the disease is usually only possible in Internet forums or a few self-help groups. Relatives should also read specialist literature and visit a specialist center for metabolic disorders. Discussions with specialists help to understand the rare syndrome and thereby come to terms with the child’s condition.
