The term peroxisomal disease summarizes genetically caused defects that affect the formation of peroxisomal, the transport of proteins or enzymes through the peroxisomal membrane or the function of peroxisomal enzymes themselves. A large number of oxygen-dependent, systemically effective reactions take place in the peroxisomes. A disturbance in the metabolic processes can, for example, have serious effects on the nerves, skeleton, retina and liver and cause serious morphological malformations of the face and head.
What is a peroxisomal disease?
Genetic disorders related to the formation or function of the peroxisomes are referred to as peroxisomal diseases. A total of 15 different diseases and syndromes are known, which are subordinate to the generic term peroxisomal disease. Peroxisomes are tiny organelles that play an important role in the breakdown of oxygen radicals. See AbbreviationFinder for abbreviations related to Peroxisomal Disease.
One of their main abilities is to convert toxic hydrogen peroxide into harmless water and oxygen molecules. This indicates that the peroxisomes are the first organelles in evolutionary history that enabled multicellular organisms not only to neutralize the toxic oxygen, but also to obtain energy from the oxidation process.
The disease can be caused by disorders in the formation and proliferation of peroxisomes or by a dysfunction in the transport of enzymes through the membrane surrounding the peroxisomes. Impairment of the biocatalytic abilities of the enzymes involved also falls under the term peroxisomal disease.
The approximately 50 different enzymes that have been detected in peroxisomes already indicate their diverse functions and the complexity of the possible forms of the peroxisomal disease. What all forms of the disease have in common is that they are caused by various genetic defects, most of which are known.
Gene mutations of non-sex-specific genes, i.e. autosomes, are responsible for most manifestations of the peroxisomal disease. Adrenoleukodystrophy, also known as Addison-Schilder syndrome, is an exception. The disease is based on a change in a gene on the X chromosome at gene locus q28.
The gene encodes a specific protein that is needed in the membrane of the peroxisomes to allow certain lipids to be transported across the membrane. In some other cases, too, transport proteins play a role, transporting certain proteins into the interior of the peroxisome.
Because the small organelles do not have ribosomes, the approximately 50 different proteins that the peroxisomes need must first be synthesized in the cell’s cytosol before they are then transported through the organelle’s membrane.
Symptoms, Ailments & Signs
Symptoms and signs of peroxisomal disease depend on which genes are altered and which disease syndromes they are associated with. Not all forms of the disease are adequately understood. In some cases, serious neurological disorders such as encephalopathy, epilepsy or deafness become noticeable.
In other cases, skeletal anomalies and severe morphological developmental abnormalities of the head and face may be present. Also, anomalies of the eyes, especially the retina, and liver dysfunction immediately after birth are often due to the peroxisomal disease. Certain symptoms, each of which is based on a defined genetic defect, are usually combined into a disease syndrome.
Diagnosis & course of disease
A diagnosis is usually made via a laboratory test with evidence of certain peroxisomal substances in the blood. Specifically, they are long-chain fatty acids such as phytanic acid, a multi-branched long-chain fatty acid that is normally metabolized by alpha-oxidation in the peroxisomes.
If the peroxisomes cannot metabolize due to a lack of phytanic acid oxidase, the phytanic acid level in the blood rises and deposits in various tissues occur. Zellweger syndrome is characterized by a complete absence of peroxisomes. Effects of the syndrome are already evident in newborns.
Misdevelopment of the head and face as well as strong psychomotor development disorders and a number of other symptoms are signs that point to the disease. Signs that are not immediately visible, such as cysts in the brain, can be detected using MRI.
However, other genetically caused maldevelopments with similar symptoms should always be compared or ruled out in the differential diagnosis. The absence of the organelles can be easily demonstrated in a culture with fibroblasts and hepatocytes. It is not possible to treat this severe metabolic disorder. The disease is usually fatal within a few months after birth.
Adrenoleukodystrophy is the only form of peroxisomal disease that is inherited in an X-linked recessive manner. Also, this type of peroxisomal disease is accompanied by a poor prognosis. The disease usually ends in death within the first ten years of life.
All peroximal diseases have a very poor prognosis. In some cases, however, life length and quality of life can be improved with the help of palliative measures. All diseases show severe metabolic disorders that lead to various complications such as liver dysfunction, skeletal abnormalities or developmental disorders of the head.
Zellweger syndrome is a particularly severe form of peroxisomal disease. This very rare disease always leads to death within the first few months of life. Hydrogen peroxide builds up in the body. There are many different symptoms, not all of which can be treated. Irregular skull growth takes place, resulting in skull deformations. Brain malformations also occur.
The other organs are also partially malformed. Heart defects, liver failure with iron storage defects, multicystic kidneys or underdeveloped lungs are observed. Life-threatening complications arise, among other things, from severe respiratory problems, poisoning due to liver failure or blood formation disorders due to iron storage defects. Adrenoleukodystrophy is another peroximal disease.
Here the prognosis is somewhat more favourable. But this disease also always leads to death up to the age of ten. This form of peroxisomal disease is characterized by numerous neurological symptoms. This disorder leads to frequent seizures. Some prolongation of life can be achieved through bone marrow transplantation. However, no curative treatment is possible here either.
When should you go to the doctor?
In the case of this disease, a visit to a doctor is usually always necessary, since self-healing does not occur and the symptoms significantly restrict the patient’s everyday life and can thus significantly reduce the quality of life. The doctor should be consulted if the person concerned suffers from deafness or epilepsy.
In the event of an epileptic seizure, you should call an ambulance or go to the hospital immediately to avoid further complications. Furthermore, disorders of the liver can indicate this disease, so that a doctor should also be consulted. The sufferer must also undergo examinations of the internal organs at regular intervals to avoid complications. Anomalies in the eyes or sudden visual problems can also indicate the disease and should be examined by a doctor.
The diagnosis of the disease can be made by various specialists, with further treatment depending heavily on the symptoms that occur. It cannot generally be predicted whether this will lead to a reduced life expectancy.
Treatment & Therapy
Unfortunately, none of the 15 known manifestations of the peroxisomal disease can be treated with a treatment that goes beyond simply treating the symptoms. Therefore, the previously known treatment and therapy options are aimed at alleviating the symptoms. Palliative treatments are also used.
An exception is the X-linked recessive inherited adrenoleukodystrophy. While unsaturated fatty acids are administered for symptomatic improvement, one option is bone marrow transplantation. Bone marrow transplantation can potentially have a significant life-prolonging effect.
Outlook & Forecast
A peroxisomal disease is a genetic metabolic defect that affects the vital oxygen supply in the body. Fifteen different disorders associated with this are grouped under the term “peroxisomal disease”. The hereditary component and the location of the disorder already suggest that the prognosis cannot include any chances of recovery.
It is also problematic that some of the associated disorders have not yet been sufficiently researched. The symptoms and sequelae associated with a disrupted or mutated gene are so varied that no overall prognosis can be given for a peroxisomal disease. It is clear that this is a group of very serious consequential defects that often end fatally. The only question is whether the peroxisomal disease diagnosed by a specialist will lead to death a few months or a few years after birth.
There are currently no more than curative treatment options for any of the 15 known peroxisomal diseases. The quality of life of those affected usually corresponds to the short lifespan. It’s not very high. In some cases it is possible to improve both parameters through intensive palliative care. The most serious peroxisomal disease is Zellweger syndrome. This leads to death within a short time after birth due to serious deformities. More than symptom-relieving or palliative treatments are not feasible in any known peroxisomal disease.
Direct preventive measures to avoid peroxisomal disease do not (yet) exist. Currently (2017) not all gene mutations are known that are considered to be the triggers of the peroxisomal disease. If there is a family history of peroxisomal disease, parents should educate themselves about the likelihood that one of their children could have the disease.
Since the peroxisomal disease is based on a genetic defect and is usually fatal within a few months after birth or at the latest by the end of the first decade of life, therapy can only alleviate a few symptoms for a short time without being able to completely cure the disease. For this reason, there is no actual aftercare treatment in this sense, but intensive symptom treatment to alleviate some suffering.
In general, those affected and their families are advised to lead a healthy lifestyle with a balanced diet to support the immune system. Furthermore, the parents of the affected infant and affected children are recommended to talk to a psychotherapist in order to promote the processing of this severe stroke of fate.
He will also suggest certain relaxation and mental techniques for stabilization and advise as many leisure activities as possible, which should bring the affected family many happy hours together. Since most children suffer from severely restricted lung function, it is recommended that they spend at least one hour outside in the fresh air every day.
If the parents who have already been affected wish to have another child, a precise genetic test is recommended to determine in advance the probability of having another child with the disease.
You can do that yourself
Dealing with the peroxisomal disease in everyday life is not always easy for those affected and their families. For this reason, mental strengthening of all those affected should take place. Mutual cohesion and the promotion of well-being are important in order to be able to record positive developments in the further course.
In addition to psychotherapeutic support, mental techniques or relaxation methods can be used. The methods help to reduce stress in everyday life and to stabilize the mind. The leisure activities should be adapted to the health possibilities. They are important so that the focus of attention is directed to the beautiful areas of life.
A healthy lifestyle is essential to avoid complications or secondary diseases. The immune system can be supported with a balanced diet. The intake of harmful substances such as nicotine, alcohol or non-prescribed medication is to be avoided. As a result, the organism is additionally stressed overall, which contributes to a worsening of the overall situation.
If breathing problems occur, it can often lead to anxiety. The person concerned should find out how best to behave if fear arises. In addition, it is important that the patient moves in the fresh air for a longer period of time every day. This serves to stabilize the immune system and helps the lungs to function properly.