Pelizaeus-Merzbacher Disease – Causes, Symptoms & Treatment

Pelizaeus-Merzbacher disease

Pelizaeus-Merzbacher disease is a hereditary leukodystrophy with degeneration of the nerve substance . Those affected suffer from a mutation-related disorder of myelination, which primarily results in motor and intellectual deficits. The therapy of the disease has so far been limited to supportive measures of physiotherapy and psychotherapy.

What is Pelizaeus-Merzbacher disease?

Leukodystrophies are genetic metabolic diseases in which the white matter of the nervous system progressively degenerates due to deficiency symptoms. Above all, the myelin that surrounds the nerves is broken down.

Myelin represents an insulation in the human organism. As in a plastic cable, the bioelectrical action potential of the nerve excitation in myelinated nerve tracts is protected from losses to the environment. Without myelin, the function of a nerve is severely impaired. Loss of excitation occurs. The stimulus conduction is difficult.

Patients with leukodystrophies therefore suffer from neurological deficits. Leukodystrophies are particularly noticeable in the motor area. Pelizaeus-Merzbacher disease is a leukodystrophy first described by the German neurologist FC Pelizaeus and the psychiatrist L. Merzbacher.

The disease is characterized by a disorder in the myelin sheath formation, which can manifest itself in a variety of different symptoms. All age groups can be affected. The prevalence is estimated at around one to nine cases in 1,000,000 people. Different literature also refers to leukodystrophy as cerebral sclerosis , diffuse familial leukodystrophy or Pelizaeus-Merzbach cerebral sclerosis .


Like all leukodystrophies, Pelizaeus-Merzbacher disease is also based on a degeneration of the white nerve substance. In the case of the disease, this degeneration corresponds to a genetic disorder in the formation of myelin sheaths. The myelin formation disorder goes back to a multiple mutation that has now been localized to the PLP1 gene.This gene codes for the proteolipid protein 1 and is located in gene locus Xq22 of the X chromosome. The type of mutation that occurs in the PLP gene can vary from case to case. The mutations can thus correspond to deletions, for example. However, duplications of the gene have also been detected in patients with Pelizaeus-Merzbacher disease.

The mutations lead to defective production of proteolipid proteins. The defective proteins in turn result in defective myelin as they play an essential role in myelin synthesis. This results in functionless myelin sheaths, which result in a loss of potential in the nerves. The disease is inherited in an X-linked recessive manner. For this reason, only the male sex usually falls ill. Women are mostly silent carriers.

Symptoms, Ailments & Signs

The main symptom of Pelizaeus-Merzbacher disease is a delay in mental and motor development . In addition to uncontrollable twitching of the eyes in the form of nystagmus , the main symptoms of the disease include spastic and flaccid paralysis of the muscles and loss of tone with atactic unsteadiness in standing and walking .

Symptoms usually first appear in infancy or childhood. However, manifestation in adulthood is also conceivable. Basically, the congenital form is usually the most difficult. Dyspnea or stridor often occur in addition to the symptoms mentioned . A spastic tetraparesis is often part of the clinical picture.

In the classic form with manifestations in the first few months of life, nystagmus and muscle hypotonia progress to spasticity . In addition to the classic and congenital form, there is a transitional form with an extent of impairment between the classic and the congenital variant. In principle, different degrees of severity are conceivable. The symptoms can be relatively wide-ranging, so that the clinical picture of the patients often differs greatly.

Diagnosis & disease progression

The neurological examination and the medical history provide the first indications of Pelizaeus-Merzbacher disease. Since no biochemical markers are available for the disease, imaging plays the most important role in diagnostics. An MRI scan of the brain reveals myelination disorders.

Since such disturbances are not specific to Pelizaeus-Merzbacher disease, a differential diagnosis must be made compared to other demyelinating diseases. Magnetic resonance spectroscopy can help with this. The final confirmation of the suspected diagnosis usually takes place in the form of a molecular genetic analysis.

A detected mutation of the PLP1 gene is considered diagnostic. In principle, prenatal diagnosis is possible. The prognosis of patients depends on the severity of the disease and the type of PLP mutation. Mild courses are just as conceivable as severe forms with a fatal course in childhood.


Because of Pelizaeus-Merzbacher disease, those affected suffer from a number of different limitations and complaints. In most cases, only very few of the complaints can be completely healed, so that the affected person is dependent on the help of other people in his life. First and foremost, patients with this disease suffer from a significantly delayed development.The motor development of the patient is also significantly restricted in this disease and there are also severe mental deficits. Those affected by Pelizaeus-Merzbacher disease also suffer from an insecure gait and various paralysis and other sensory disorders. Sometimes there are signs of spasticity. In many cases, bullying or teasing can occur, especially in children, so that patients with Pelizaeus-Merzbacher disease also develop mental health problems and depression.

A causal treatment of Pelizaeus-Merzbacher disease is not possible. The disease is a major psychological burden, especially for the parents and relatives. Furthermore, some symptoms can be reduced with the help of therapies. However, there is no complete cure for this disease. It may also reduce the patient’s life expectancy.

When should you go to the doctor?

Since Pelizaeus-Merzbacher disease leads to severe delays in child development, this disease must always be examined and treated by a doctor. This is the only way to avoid further complications. The sooner treatment for Pelizaeus-Merzbacher disease is started, the higher the chances of a full recovery.

A doctor should be consulted if the child suffers from paralysis or an unsteady gait. The paralysis can affect different parts of the body. Likewise, the motor or mental development of the child can be significantly restricted and delayed. Should the parents notice these delays, a doctor must be consulted immediately. Some children also have spasticity due to Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease is usually diagnosed by a pediatrician or general practitioner . However, further treatment takes place with various specialists and depends on the exact severity of the symptoms. Psychological treatment, in which both the parents and the children can take part, is often useful for Pelizaeus-Merzbacher disease. The life expectancy of those affected is usually not negatively reduced by Pelizaeus-Merzbacher disease.

Treatment & Therapy

Pelizaeus-Merzbacher disease is caused by genes. For this reason, there is currently no causal therapy for patients with the disease. Causal forms of therapy could at most open up gene therapy . Gene therapy approaches are currently a focus of medical research.

However, the approaches have not yet reached the clinical phase. Therefore, patients with Pelizaeus-Merzbacher disease are currently treated purely symptomatically and supportively. The individual treatment steps depend on the symptoms present in each individual case. Therapy focuses on supportive measures that delay the course and improve the quality of life of those affected.

These measures primarily include ergotherapy and physiotherapy . Mental development can be supported by early intervention. In addition, relatives of those affected receive emotional support. Parents are often provided with a psychologist or psychotherapist , for example . Contacts are established with the European Association against Leukodystrophies. Various university clinics also offer special consultation hours.

Outlook & Forecast

Pelizaeus-Merzbacher disease is chromosomal. It comes in three different forms. This is determined by the age of onset and the severity of the disease and its severity. These parameters then also influence the prognosis. Male patients mainly suffer from this very rare disease.

The congenital variant of the disease has the most serious symptoms. If the Pelizaeus-Merzbacher disease only breaks out after birth, the symptoms gradually develop in different forms. The prognosis of the transitional form lies between congenital and classic Pelizaeus-Merzbacher disease. However, there are also milder courses of Pelizaeus-Merzbacher disease. Depending on the type, the prognosis for this disease varies.

Without interdisciplinary treatment by neurologists , orthopaedists , physiotherapists , gastroenterologists and pulmonologists , patients cannot be helped sufficiently. The progressive course of the disease varies depending on the phenotype. Life expectancy does not necessarily have to be restricted if Pelizaeus-Merzbacher disease is present. At least in the milder courses, it is relatively normal. The disease often progresses more slowly in adolescence. How high the quality of life can be depends on the clinical picture.

The prognosis for severely affected people is different. These usually die before the age of twenty. Until then, those affected can only be relieved by means of symptomatic treatment.


So far, Pelizaeus-Merzbacher disease can only be prevented by genetic counseling during the family planning phase. Depending on your own inheritance risk, you may decide not to have your own child. In addition, prenatal diagnostics can be carried out if necessary.


Those affected with Pelizaeus-Merzbacher disease usually only have a few measures and options for aftercare. In the case of this disease, rapid and, above all, early detection of the disease is very important in order to prevent further complications or symptoms. Those affected should consult a doctor as soon as the first signs and symptoms of the disease appear in order to prevent further deterioration of the symptoms or further complications.

As a rule, those affected by Pelizaeus-Merzbacher disease are dependent on measures of physiotherapy or physical therapy, whereby self-healing cannot occur. Many of the exercises from these therapies can also be repeated at home. Since this is a genetic disease, those affected should carry out a genetic examination and counseling if they wish to have children, so that the Pelizaeus-Merzbacher disease cannot recur in the children and descendants.

Since the disease can also lead to depression and other psychological upsets, the help and support of one’s own family and friends is often very important. Pelizaeus-Merzbacher disease does not usually reduce the life expectancy of the person affected.

You can do that yourself

Since Pelizaeus-Merzbacher disease is genetic, there are no self-help measures that combat the cause of the disorder. In most cases, the disease manifests itself in childhood, so it is up to the parents and families of the patients to take appropriate measures in good time.

Affected parents should first ensure that their child is being treated by a doctor who has experience with this relatively rare disease. If the family doctor cannot recommend an expert, the medical association can help. Many university clinics have special consultation hours in which patients and their relatives can obtain comprehensive information about the disease and its course. It is important for young parents to deal with what awaits them and their sick child at an early stage. It is easier for well-informed parents to find a childcare place in good time and later a school that guarantees their child the best education within the scope of their possibilities.

In addition, caring for and living with a disabled child is also a major challenge for the relatives. Those affected should therefore not be afraid to seek help for themselves. Talking to other people affected often helps. The European Association against Leukodystrophies can help you get in touch.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.