Krabbe disease is a hereditary storage disease that causes demyelination of the nervous system. It is caused by a chromosomal mutation. To date, the disease is incurable.
What is Krabbe disease?
Krabbe disease is a rare storage disease in the cerebroside family. The disease is also known as globoid cell leukodystrophy. The disease is named after the Danish physician Knud Krabbe. He was the first to describe the autosomal recessive disease in detail. In Krabbe 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 begins in adulthood. Gaucher’s disease is to be distinguished from Krabbe’s disease. This is also a hereditary storage disease based on a gene mutation. In both diseases, the affected individuals lack an enzyme. In Krabbe 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 underlying cause of Krabbe disease is a defect in the GALC gene. This gene sits on chromosome 14 and is located in section q3.1. During biological translation, mRNA is translated into proteins upon submission. 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 disease, a deletion takes place, which means that the affected person completely lacks the enzyme galactocerebrosidase. As a consequence, substances accumulate in the organism that are produced during myelin metabolism. Myelin is the insulation of 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. Galactocerebroside and psychosine in particular accumulate. Psychosine is harmful to oligodendrocytes, which ensure the maintenance of myelin.
Symptoms, complaints, and signs
Patients of Krabbe disease are affected by symptoms similar to those of multiple sclerosis. Both diseases are associated with demyelination of the nerve pathways. Initially, this demyelination often manifests itself in sensory disturbances. Due to the degradation of the myelin, the nerve conduction velocity of the patients is reduced. Depending on which area of the nervous system is currently affected, motor and cognitive impairments may develop. Paralysis is conceivable, but the ability to perceive is also impaired. Under certain circumstances, blindness may occur, for example. Deafness is also a possibility. As a rule, the patient’s reflexes can no longer be triggered. In infantile Krabbe disease, symptoms usually begin when the infant is only a few months old. The affected infants suffer crying attacks and are easily irritated. The legs often stretch tonically in response to external stimuli. Development comes to a halt and the arms flex permanently. Hyperventilation and fever occur.
Diagnosis and course of the disease
When diagnosing Krabbe disease, the physician must consider multiple sclerosis as the primary differential diagnosis. A CSF sample may provide information about the cause of demyelination. In multiple sclerosis, immunoglobulins are found in the CSF despite the blood–brain barrier. In Krabbe disease, on the other hand, the proteins are elevated. Galactocerebrosidase can be detected in the leukocytes to confirm the diagnosis. Fibroblast cultures can also help to confirm the diagnosis. The same applies to genetic analysis, which reveals a mutation of the corresponding chromosome. For the infantile form of Krabbe disease, the prognosis is unfavorable. Affected individuals die at an average age of 13 months. For the adult-onset special form, the prognosis is more favorable because the disease progresses more slowly in this case.
Complications
In most cases, those affected with Krabbe disease suffer from various disorders of sensitivity and paralysis. As a result, the patient’s daily life is significantly restricted and the affected person is dependent on the help of other people. The patient’s quality of life is also significantly reduced by Krabbe disease.It is not uncommon for the disease to lead to cognitive or motor impairments, which can significantly affect children’s development. Furthermore, children may be teased or bullied, which can often lead to depression or other psychological problems. Furthermore, Krabbe disease can cause blindness or lead to deafness. Especially in young people, sudden blindness can lead to severe depression. Babies often cry because of the symptoms and also suffer from fever. The relatives or parents may also suffer from mental discomfort or depression due to the disease. Treatment can usually be done only with the help of medications. However, transplantation of stem cells is also possible. In this case, no particular complications occur. Under certain circumstances, the life expectancy of the affected person is reduced by Krabbe disease.
When should one go to the doctor?
The classic form of storage disease, Krabbe disease, is apparent in early childhood. If the family is aware of the heritability of the disease, the trip to the doctor is quick. The risk that a child in the family will develop Krabbe disease is high. Siblings, however, have only a 1 in 4 chance of contracting the disease. Krabbe disease is often discovered during prenatal diagnosis. Since the disease cannot be cured, abortion is possible on medical indication. Globoid cell leukodystrophy is always fatal in the infantile form. The children usually die before they reach the age of one. Apart from symptom-relieving administration of painkillers for palliative purposes, there is not much for the treating physician to do. The physician may also prescribe muscle-relaxing preparations and sedatives. In the case of the later occurring special forms of Krabbe’s disease, the therapeutic options are equally poor. The course of the disease is slower, and the symptoms may not be quite as severe. In the late form of Krabbe disease, physicians can sometimes achieve improvements with stem cell transplantation.
Treatment and therapy
Krabbe disease is considered incurable. No causative therapy is available. Unlike the demyelination of multiple sclerosis, the progression of Krabbe disease also cannot be delayed. Therefore, instead of prolonging life, the therapeutic focus is on improving the quality of life. To achieve this goal, drug therapies with antispasmodic spasmolytics are often used. Painkillers and sedatives can also achieve symptomatic positive effects. Parents of affected children usually receive psychotherapeutic care. In late forms of Krabbe disease, unlike the infantile form, a delay in the course of the disease is possible. In this respect, stem cell therapies have achieved good results. In this therapy, blood stem cells from a donor are transferred to the patient. However, this allogeneic stem cell transplantation is always a risky affair. Especially inflammatory reactions and infections are within the realm of possibility. With progress in the field of gene therapy, it may be possible in the future to cure Krabbe disease sufferers. At the moment, however, this scenario is still a long way off.
Outlook and prognosis
Krabbe disease offers a poor prognosis. Many children die within 12 to 13 months after 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. Until the death of the child, the symptoms progress until finally a largely unresponsive state occurs. Death occurs as a result of complications such as respiratory arrest or cardiovascular failure. The late infantile or juvenile form of Krabbe disease offers a more favorable prognosis. Children afflicted with the juvenile form can live for several years. 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. For the child and the relatives, the disease means a great burden.Therefore, affected families receive detailed counseling, during which prognosis and treatment options are also discussed. The association ELA Deutschland e. V. provides further details on the prognosis of Krabbe disease.
Prevention
Chromosome mutations such as Krabbe disease cannot be prevented directly. However, families in the process of planning children can have the risk of passing on inherited diseases assessed via sequence analysis of their DNA. If one child was affected by Krabbe disease, there is about a 25 percent chance of further children developing the disease.
Follow-up
As a genetic condition, Krabbe disease is currently incurable, and accordingly there is no medical aftercare in the strict sense. The course always ends fatally. If the disease occurs in childhood or after birth, parents should be well informed about Krabbe disease and the therapy. Symptomatic therapy is then given first, mainly to control irritability and spastic paralysis. It then comes to later stages of the disease mainly palliative measures. People with later onset of the disease show the same symptoms. However, the progression is slower, which can give relatives more time to prepare and still spend time with the person suffering from Krabbe disease. Aftercare for relatives consists of psychological support, 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 conceivable. However, this cannot provide a cure either. If a stem cell transplantation is attempted, the necessary aftercare measures are added. This means, for example, a special protection of the recipient against germs, because his immune system must be weakened for the therapy.
Here’s what you can do yourself
Krabbe disease is not curable so far. 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 applied quickly in the event of convulsions. In addition to painkillers, physical exercise and distraction can also bring relief. In any case, the typical motor and cognitive impairments must be treated in a specialized clinic. Parents should talk to the doctor in charge about further therapy options, as research into this rare hereditary disease is progressing rapidly and new treatment methods are being found all the time. The actual multiple sclerosis can be treated by physiotherapy, massages and various relaxation exercises. This can effectively alleviate typical symptoms such as tremors or dizziness. Regular pelvic floor training can help with potency problems. The quality of life of both child and parents can also be improved by comprehensive psychological counseling. 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. In parallel, organizational tasks such as enrollment in special kindergartens and the purchase of assistive devices must be taken care of.
