Krabbe Disease

1 What is Krabbe Disease?

Krabbe is an inherited disease that affects the myelin sheath which serves to protect the nerves. The most common signs of this disease are that it starts early, before the age of 6 months of age. It also results in early death before the end of the 2nd birthday. However, the disease varies when it develops in older children and adults.

Most importantly, is that there is no cure for Krabbe disease and the only available treatment is supportive care. Stem cells transplant has been suggested as a possible alternative treatment and has shown success in infants treated before the emergence of the symptoms in older children and adults.

Epidemiology studies show that the disease affects about 1 in every 100,000 children in the US. It has also been referred to as the globoid cell leukodystrophy.

2 Symptoms

The symptoms of Krabbe disease occur within the first few months of life. The symptom begins gradually and progressively gets worse. In infants, the common signs and symptoms may include challenges in feeding, constant crying, irritability, fever even in an absence of infection, dormant, slow growth/retarded growth, Muscles spasms, loss of control of the head, constant vomiting.

The increase in the severity of the disease may promote seizures, loss of growth abilities, loss of hearing and sight, constricted muscles, fixed postures, progressive loss of ability to swallow and breathing.

The signs and symptoms also vary when it develops in older adults children. However, the younger the age, the higher the disease progression and can lead to death.

In adulthood or adolescence, the symptoms may be less severe. At this age, the main characteristic of the disease is muscle weakness. No impairment of the thinking skills occurs at this age.

When this disease occurs in infancy, it is an indication of the possibility of developing a number of conditions and developmental problems. Seeing a doctor is, therefore, important for the prompt and accurate diagnosis of the disease.

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3 Causes

Krabbe disease is caused when a person inherits two copies of an altered gene from each of the parents. The gene is the blueprint for the production of proteins. In the case of error in the formation of the blueprint, therefore, the protein formed may not be biologically functional.

In Krabbe disease, inheritance of two mutated copies of the gene lead to little or no production of the enzyme referred to as galactocerebrosidase (GALC). This enzyme has a role in the breakdown f substances in the cells recycling center which is located in the lysosome. Short supply of this enzyme, therefore, leads to the accumulation of the fats called gactolipids.

Damage to the nerve cells causes the interference with the galactolipids which are present in the cells that produce and sustain the protective coating of the nerve cells (myelin sheath). Overabundance of the gactolipids on the other hand has toxic effects on the body. They may initiate the myelin forming cells to undergo self-destruction.

Other galactolipids may cause their uptake by the specialized debris eating cells in the nervous system referred to as the microglia. The process of cleaning the excess galactolipids may transform the normal helpful cells to abnormal cells referred to as globoid cells. This causes the myelin-damaging inflammations.

Demyelination reduces the ability of the nerves to send and receive signals or messages from other parts of the body.

4 Making a Diagnosis

Krabbe disease can be diagnosed in newborns with improved screening techniques even before the symptoms can be seen. This may require a specialist of the nervous system (neurologists) at the time the disease has been diagnosed. However, the start of the symptoms may be the trigger for a number of possible causes.

This requires frequent possible baby visits and appointments during childhood. The doctor will monitor key aspects such as the development of your children in the growth of the muscles, coordination, posture, age-associated motor skills, sensory abilities, vision and hearing and touch.

One needs to plan on how to respond to the doctor’s questions.  

  • When did the symptoms start?
  • Have the symptoms changed?
  • How is the attentiveness of your child?
  • Does he have a fever?
  • Is there excessive irritability

The nature of the questions will vary with the age of the child that is affected. A series of tests can be done for diagnosis of the disease which may involve the collection of the blood sample and skin biopsy.

Very low or no GALC activity will indicate the presence of Krabbe disease. This will only provide evidence of the disease but may not indicate the progression of the disease.

Imaging tests can also be done to confirm the diagnosis of the loss of the myelin sheath as a result of the demyelination in the regions of the brain. Magnetic resonance imaging may be applied, Computerized tomography (CT) may be used.

Nerve conduction studies may also be performed to determine the rate at which the nerve conducts the signal. This uses a special electrical impulse to travel from one point to another point of the body. The signal conduction is slower in an impaired myelin nerve.

Genetic testing can also be done on a blood sample to verify the diagnosis. This will also indicate the specific type of mutation and help determine the expected course of the disease.

Newborn screening tests for Krabbe disease are present in some states of the United States. They measure the GALC enzyme activity, when determined to be low, then the follow-up test can be done and genetic test used to confirm the findings. 

Use of newborns is a new technique and researchers are yet to comprehend fully how this can be best used as a screening technique and to increase specificity and accuracy in the diagnosis of the disease.

5 Treatment

There is no recommended treatment for infants that have developed these symptoms of Krabbe disease. However, the patient care strategies may involve the management of the symptoms and offering of the supportive care.

Seizures are managed by use of anticonvulsants drugs for managing irritability of muscles, physical therapy to manage the deterioration of muscles, nutritional support to deliver fluids and other nutrients to the stomach using the gastric tubes. This may also be applied to older children’s and adults.

Stem cells transplantation for hematopoietic stem cells can also be performed for children so as to grow and develop into different forms of body cells. The cells may also serve as a source of microglia which is a specialized form of debris eating cells that reside in the nervous system. However, in the Krabbe's disease, the microglia can be converted into toxic globoid cells.

The stem cells are delivered to the recipient’s blood stream through a tube called the central venous catheter. The stem cells will contribute to the formation of healthy microglia which can populate the nervous system and promote the formation of functioning GALC enzymes. This may restore the production of the normal myelin.

It has been suggested that this significantly improves the treatment for onset symptoms in infants. It has been shown that he Presymptomatic infants on stem cells transplant develop a slower disease progression, however, the children would still experience challenges in speech, walking and other motor activities.

Older children and adults can also be beneficiaries of the treatment. Some of the potential sources for hematopoietic stem cells may include the umbilical cord blood donor, bone marrow and circulating blood stem cells.

6 Lifestyle and Coping

Lifestyle modifications are necessary in order to cope with Krabbe disease.

There are organizations that offer support and other educational resources.

You may also need to use networking opportunities and services to families that deal with Krabbe diseases.

7 Risks and Complications

There are several risks and complications associated with Krabbe disease.

Mutation in the gene that is associated with Krabbe disease only leads to the disease of the mutated copies of the genes is inherited. A disease that develops from a two mutated copies is referred to as an autosomal recessive disorder.

When each of the parents has mutated copies of the gene, the child will be at 25% risk of inheriting the mutated copy of the genes. A 50% chance of inheriting only one copy of the mutated gene makes the child a carrier of the disease.

In addition, genetic testing can be considered only in situations where one or both parents are the likely carriers of the GALC gene mutation as a result of the known history of the disease.

It is important for a family to test for Krabbe to understand the risk of the disease. The parents that are known carriers can also request for a prenatal genetic test as a way of determining if a child is likely to develop a disease.

Even known carriers receiving in vitrio fertilization can also request for genetic testing with the fertilized egg before the implantation. It is also important to consider genetic counseling to assess the benefits, limits, and implications of genetic testing.

Some of the complications may include infections and respiratory difficulties which can develop in children with Krabbe disease. In later stages of the disease, the children can become incapacitated and become restricted to their beds.

Often, most of the children with the disease die before the age of 2. They also develop respiratory failures, Immobility, a decline in the muscle tones, longer life expectancy for children that develop it later in life.

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