Krabbe’s disease is an inherited storage disease that causes demyelination of the nervous system. The cause of this phenomenon is a chromosomal mutation. So far the disease is incurable.
What is Krabbe’s disease?
Doctors understand Krabbe’s disease to be a rare storage disease from the cerebroside family. The condition is also known as globoid cell leukodystrophy. The disease is named after the Danish doctor Knud Krabbe. He described the autosomal recessive hereditary disease in detail for the first time. In Krabbe’s disease, toxic compounds accumulate in the body due to a gene mutation. In addition to the infantile form, there is a special form of the disease that only sets in in adulthood. See homethodology for Hepatic Hemangioma Overview.
Gaucher’s disease must be distinguished from Krabbe ‘s disease. This is also a hereditary storage disease based on a gene mutation. In both diseases, those affected lack an enzyme. In Krabbe’s disease, it is the enzyme β-galactosidase. Without galactocerebrosidase, demyelination of the nervous system occurs. Gaucher disease, on the other hand, involves the enzyme glucocerebrosidase, the absence of which has other effects on the organism.
Causes
The cause of Krabbe’s disease is a defect in the GALC gene. This gene is located on chromosome 14 and is located in section q3.1. In biological translation, the mRNA is translated into proteins based on the template. During translation, the GALC gene is the blueprint for the enzymatic galactocerebrosidase. A defect in this gene causes errors in translation. In the case of Krabbe’s disease, a deletion takes place, which means that the affected person completely lacks the enzyme galactocerebrosidase.
As a result, substances that are produced during myelin metabolism accumulate in the organism. Myelin is the insulation of the nerve fibers in the nervous system. The enzyme galactocerebrosidase breaks down the metabolites of myelin into galactose and galactocerebrosides. If the enzyme is missing, this splitting can no longer take place. Above all, galactocerebroside and psychosin accumulate. Psychosin is harmful to oligodendrocytes, which ensure the maintenance of myelin.
Symptoms, Ailments & Signs
Patients with Krabbe’s disease are affected by similar symptoms as patients with multiple sclerosis. Both diseases are associated with demyelination of the nerve tracts. This demyelination is initially noticeable in sensory disturbances. Due to the degradation of the myelin, the patient’s nerve conduction speed is reduced. Depending on which area of the nervous system is currently affected, motor and cognitive impairments can occur.
Paralysis is conceivable, but the ability to perceive is also impaired. For example, blindness may occur. Deafness is also within the realm of possibility. The reflexes of the patients can usually no longer be triggered. In infantile Krabbe’s disease, the symptoms usually begin at an age of just a few months. Affected infants suffer crying attacks and are easily irritated. The legs often stretch tonic in response to external stimuli. The development comes to a standstill and the arms bend permanently. Hyperventilation and fever set in.
Diagnosis & course of disease
When diagnosing Krabbe’s disease, the doctor must primarily consider multiple sclerosis in the differential diagnosis. A cerebrospinal fluid sample can provide information about the cause of the demyelination. In multiple sclerosis, immunoglobulins are found in the liquor despite the blood-brain barrier. In the case of Krabbe’s disease, on the other hand, the proteins are increased. Galactocerebrosidase can be detected in the leukocytes to confirm the diagnosis.
Fibroblast cultures can also help confirm the diagnosis. The same applies to a genetic analysis that reveals a mutation in the relevant chromosome. The prognosis for the infantile form of Krabbe’s disease is unfavorable. Those affected die at an average age of 13 months. The prognosis is more favorable for the special form in adulthood, since the disease progresses more slowly in this case.
Complications
In most cases, those affected by Krabbe’s disease suffer from various sensory disorders and paralysis. As a result, the everyday life of the patients is significantly restricted and those affected are dependent on the help of other people. The patient’s quality of life is also significantly reduced by Krabbe’s disease.
It is not uncommon for the disease to also lead to cognitive or motor impairments and can thus also significantly impair the development of children. Furthermore, children can also be teased or bullied, which can often lead to depression or other psychological problems.
Furthermore, Krabbe’s disease can cause blindness or lead to deafness. Sudden blindness can lead to severe depression, especially in young people. Babies often cry because of the symptoms and also suffer from fever. Relatives or parents can also suffer from psychological problems or depression as a result of the disease.
Treatment, as a rule, can only be carried out with the help of medication. However, stem cell transplantation is also possible. There are no particular complications. The life expectancy of those affected may be reduced by Krabbe’s disease.
When should you go to the doctor?
The classic form of the Krabbe disease storage disease is already recognizable in early childhood. If the family knows that the disease can be inherited, then going to the doctor is quick. The risk that a child in the family will contract Krabbe’s disease is high. The siblings, however, only get sick with a 1:4 chance. Krabbe’s disease is often discovered during prenatal diagnosis.
Since the disease cannot be cured, an abortion is possible if medically indicated. Globoid cell leukodystrophy is always fatal in the infantile form. Children usually die before they are one year old. Apart from administering painkillers to alleviate the symptoms for palliative purposes, there is not much left for the attending physician to do. The doctor can also prescribe muscle relaxants and sedatives.
The treatment options are just as poor for the special forms of Krabbe’s disease that occur later. The course of the disease is slower, the symptoms may not be quite as serious. In the late form of Krabbe’s disease, doctors can sometimes achieve improvements with a stem cell transplant.
Treatment & Therapy
Krabbe’s disease is considered incurable. A causal therapy is not available. Unlike the demyelination of multiple sclerosis, the course of Krabbe’s disease cannot be delayed. Instead of prolonging life, the therapeutic focus is therefore on improving the quality of life. In order to achieve this goal, drug therapies with antispasmodic spasmolytics are often carried out.
Painkillers and sedatives can also have positive symptomatic effects. The parents of affected children are usually treated psychotherapeutically. In late forms of Krabbe’s disease, unlike in the infantile form, a delay in the course of the disease is possible. In this regard, stem cell therapies have achieved good results. Blood stem cells from a donor are transferred to the patient as part of this therapy.
However, allogeneic stem cell transplantation is always a risky affair. Inflammatory reactions and infections in particular are within the realm of possibility. With advances in the field of gene therapy, it may be possible in the future to cure patients with Krabbe’s disease. At the moment, however, this scenario is still a long way off.
Outlook & Forecast
Krabbe disease has a poor prognosis. Many children die within 12 to 13 months of birth. Life expectancy can be extended by stem cell transplantation. A cure for the genetic disease is not yet possible. The condition can only be treated palliatively. The symptoms progress until the child dies, until a largely unresponsive state finally sets in. Death occurs as a result of complications such as respiratory failure or cardiovascular failure.
The late infantile or juvenile form of Krabbe’s disease offers a more favorable prognosis. Children suffering from the juvenile form can live to be several years old. The first symptoms appear much later, which means that the development of the immune system is already largely complete. The better protection of the body opens up additional treatment options and the prospect of a relatively symptom-free life.
However, the juvenile form is also lethal. The illness is a great burden for the child and the relatives. For this reason, affected families receive detailed advice, during which the prognosis and treatment options are also discussed. The association ELA Germany e. V. provides further details on the prognosis of Krabbe’s disease.
Prevention
Chromosome mutations such as Krabbe’s disease cannot be prevented directly. Families planning children can, however, use the sequence analysis of their DNA to assess the risk of passing on hereditary diseases. If a child was affected by Krabbe’s disease, there is a probability of around 25 percent for other children.
Aftercare
As a genetic condition, Krabbe’s disease cannot currently be cured and there is accordingly no medical follow-up care in the narrower sense. The course always ends fatally. If the condition occurs in childhood or after birth, parents should be well informed about Krabbe’s disease and the therapy. Only then is there symptomatic therapy, which is primarily intended to control irritability and spastic paralysis. In the later stages of the disease, mainly palliative measures are used.
People who develop the disease later show the same symptoms. However, the progression is slower, which can give family members more time to prepare and still spend time with the Krabbe sufferer. Follow-up care for relatives consists of psychological care, if this is desired. A genetic test can also provide information about the risk of further offspring suffering from Krabbe disease.
A stem cell transplant is possible. However, no healing can be brought about by this either. If a stem cell transplant is attempted, the necessary aftercare measures are added. This means, for example, that the recipient is given special protection against germs because their immune system has to be weakened for the therapy.
You can do that yourself
There is currently no cure for Krabbe’s disease. The parents of affected children therefore often need therapeutic support. Drug treatment can be supported by various measures. First, the child must be observed around the clock so that the necessary medication can be used quickly in the event of cramps. In addition to painkillers, physical exercise and distraction can also provide relief.
The typical motor and cognitive impairments must always be treated in a specialist clinic. Parents should talk to the responsible doctor about further treatment options, since research into the rare hereditary disease is progressing rapidly and new treatment methods are constantly being found. The actual multiple sclerosis can be treated with physiotherapy, massages and various relaxation exercises. This effectively alleviates typical symptoms such as tremors or dizziness. Regular pelvic floor training can help with potency problems.
The quality of life of child and parents can also be improved through comprehensive psychological counselling. Especially after a longer phase of illness, it is necessary to discuss the life situation with a specialist and to work out new treatment approaches. At the same time, organizational tasks such as registering for special kindergartens and purchasing aids have to be taken care of.
