Krabbe Disease

Krabbe Disease is a rare genetic disorder that often turns fatal for its sufferers. Read and know what this condition is like, what are its causes, how it can be treated and more.

Krabbe Disease Definition

It is a rare disorder of the nervous system. This condition affects the myelin sheath and may become a life threatening degenerative disorder. It is associated with dysfunctional metabolism of the sphingolipids, which makes it a type of Sphingolipidosis. The inheritance of this condition occurs in the autosomal recessive pattern.

The disease has been named after Knud Haraldsen Krabbe, a neurologist from Denmark.

Krabbe Disease Synonyms

This disease is often referred to by other names like:

  • Globoid Cell Leukodystrophy
  • Galactosylceramide Lipidosis
  • Galactosylceramidase Deficiency

Krabbe Disease History

The disease was first identified in several newborn babies in 1916 by Knud Haraldsen Krabbe. He studied five babies from 2 families who were suffering from severe irritability and episodes of crying before reaching 6 months of age. In later stages, these infants developed spasms that were triggered by noise, light and touch. Finally, all these babies died even before growing 2 year old. It was Krabbe who identified the cause of death and stated that the brain cells of the victims were lacking proper enzymes. Naturally, the disease had been named after him.

Krabbe Disease Types

The condition has been divided into four types, depending on the age of onset of its symptoms:

Type 1 or Infantile

It has an early onset. The symptoms begin when the child is 3 to 6 months old.

Type 2 or Late infantile

In this type, the symptoms begin to manifest sometime between the ages of 6 months and 3 years.

Type 3 or Juvenile

The onset of its symptoms occurs when the patient is 3 years to 8 years old.

Type 4 or Adult onset

This form can affect an individual anytime after the age of 8 years.

Krabbe Disease Causes

It is caused by mutations in the GALC gene. A genetic defect, which leads to the deficiency of galactocerebrosidase or GALC enzyme, is the main cause for this genetic disorder. This enzyme is responsible for maintaining the myelin, the fatty substance which is essential for the insulation of the nerve fibers.

The disease affects children who inherit the defective gene (causative of the condition) from both parents. This pattern of inheritance is known as autosomal recessive. The particular gene that causes Krabbe Disease is situated on chromosome 14.

Krabbe Disease Pathophysiology

A deficiency of the GALC (galactocerebrosidase) enzyme leads to this rare disorder. This condition is often referred to as Globoid Cell Leukodystrophy by doctors. Globoid cells are known to store molecules known as Galactolipids. GALC deficiency causes accumulation of Galactolipids inside the brain. The Galactolipid, which is believed to cause major damage to sufferers, is known as Psychosine. When the level of Psychosine becomes extremely high, the cells developing Myelin starts to self-destruct.

Krabbe Disease Genetics

Babies born to parents carrying the abnormal gene (responsible for the disorder) are at 25% risk of having the condition. If only one of the parents carry the defective gene, the offspring would also carry it but will never suffer from its symptoms.

Krabbe Disease Risk Factors

Inheriting one abnormal gene from both parents triggers the fatal condition in the newborn baby. However, even if both parents carry the defective gene, it does not necessitate that the child will develop this disease.

Krabbe Disease Stages

This neurological condition advances through three different stages:

Stage 1

This stage begins when infants are between 3 and 6 months of age. It is characterized by irritability, difficulty in feeding and high muscle tone.

Stage 2

In this stage the nerve cells are damaged more rapidly, leading to increased muscle tone, damaged vision and seizures.

Stage 3

It is the last stage of the disease and makes patients deaf, blind and unaware of their surroundings.

Krabbe Disease Signs and Symptoms

The symptoms that results from the Early Onset type differ from those arising from Late Onset. The Early Onset form includes the problems arising from both Type 1 and Type 2.

Early Onset Krabbe Disease Symptoms

This is a relatively common form of the condition that occurs during the early stages of life. It is characterized by the following symptoms:

  • Unexplained crying
  • Feeding difficulties
  • Extreme Irritability
  • Vomiting
  • Fever
  • Seizures
  • Growth failure
  • Progressive loss of sight and hearing
  • Spasms or muscle contractions
  • Changing muscle tone

Late Onset Krabbe Disease Symptoms

The late onset form develops in the later stages of childhood or during adolescence. Patients suffering from this type may experience all the above symptoms in addition to the following ones:

  • Visual impairment, that leads to blindness
  • Walking difficulty (also known as gait disturbances and Ataxia)
  • Difficulty with manual dexterity

The disease generally progresses faster in patients in whom it occurs at earlier ages. People diagnosed with the condition in adolescence or in adulthood may develop less-severe symptoms as compared to infants who test positive for this disease. Muscular weakness is the primary symptom of this form.

Krabbe Disease Prevention

There are no known ways to completely prevent this genetic disorder. However, pre-pregnancy screening and newborn screening helps understand and reduce the risk of having a baby affected by the condition.

Pre-Pregnancy Screening

Couples having a family history of this disease should undergo a genetic counseling before considering having children. This helps would-be parents understand the chances of having a baby with this disorder. It is advisable that couples consult a professional even if either of them have any extended family members with the condition.

Newborn Screening

The onset of the symptoms in a newborn can be delayed by stem cell transplants. However, this process only works before the manifestation of the initial symptoms. Naturally, screening newborns is very important at this stage. Universal newborn screening has been adopted in the state of New York for Krabbe Disease. Even in the cases when transplantation of the stem cells is not possible, newborn screening can detect the presence of the disease. This helps improve the quality of life of an affected infant by early supportive care.

Krabbe Disease Diagnosis

The doctor first analyzes all the signs and symptoms of the patient through a detailed physical examination. In the next stage, various diagnostic tests are conducted to ascertain the presence of the disease.

Blood Test

Blood test helps to determine the level of galactosylceramidase enzyme in the patient’s body. The level of this enzyme is low in the white blood cells of individuals suffering from this condition. However, this test alone cannot decide the severity of the disease.

Imaging Scans of the Head

Magnetic Resonance Imaging (MRI) creates a detailed image of the patient’s brain using magnetic signals. MRI is one of the best tests to diagnose this condition by detecting any brain abnormality that might be associated with it. However, the MRI may be normal when the disease is at its early stage. The Computed Tomography (CT) scan produces 2-D X-ray images of the head of patients by high-resolution imaging technique.

Nerve Conduction Studies

These are done to measure the velocity of the impulses in the nervous system. In these tests, the nerves are electrically stimulated for measuring the time required for the impulse to reach the recording device from the original stimulation site. The conduction of the nerve is slower if the myelin is impaired.

Eye Examination

The retina is examined by an ophthalmologist who checks if there is any indication of visual deterioration.

Genetic Testing

It helps detect any genetic mutation associated with the disease.

Krabbe Disease Differential Diagnosis

The differential diagnosis of this disease should aim at distinguishing it from a few conditions that cause similar symptoms. These include:

  • Gaucher Disease
  • Metachromatic Leukodystrophy
  • GM2 Gangliosidoses
  • Niemann-Pick Disease

Krabbe Disease Treatment

There are no specific therapies or medications that can completely cure the disease. Its treatment mainly depends on the symptoms that are present. Some of the treatment options, commonly used for this purpose, include:

  • Anticonvulsant medications, which help manage seizures.
  • Drugs like Benzodiazepine, which help reduce irritability and muscle spasticity.
  • Drugs that help reduce the occurrence of reflux.

Older children, who have less severe symptoms, can be treated by:

  • Physical therapy, which helps control the deterioration in the muscle tone.
  • Occupational therapy, which helps patients to be as independent as possible by enabling them to learn brushing teeth, eating and brushing on their own.

According to current researches, bone marrow transplantation and cord blood transfusion can be considered as effective treatment options for Krabbe Disease.

Bone Marrow Transplantation

Bone marrow is the sponge-like material located in the bones of an individual. The process of transplanting it is known as hematopoietic stem cell transplantation. Adult bone marrow can be used for replacing the bone marrow of an affected child. This transplantation is mainly beneficial for children with less-severe symptoms and to newborns diagnosed at birth. However, this treatment is not very effective in children who have already developed the deadly symptoms.

Cord Blood Transfusion

Blood stem cell transfusion has been proven effective in reducing the neurological symptoms caused by this condition.

Krabbe Disease Complications

The central nervous system suffers severe damage due to this disorder. The possible complications include:

  • Deafness
  • Blindness
  • Severe muscle tone problems

Krabbe Disease Prognosis

The outcome of this condition is poor in most cases. It is worse for those who develop the symptoms in infancy rather than in their adolescence. Individuals with the Late Onset form of the disease are known to have survived to reach their adulthood. However, they suffer from serious nervous system disease.

Krabbe Disease Prevalence

The ORD or Office of Rare Diseases of the NIH or National Institutes of Health has listed this genetic condition as a “rare disease”. According to studies, 1 in every 125 individuals carries the defective gene responsible for the condition. In the United States, 1 out of every 100,000 infants is born with the condition and die of it.

It can affect any ethnic group but is more commonly seen in Israeli people. An Israeli community named Druze has a very high incidence of this disease. Six out of every 1000 infants born in this community develop this life threatening disease.

Krabbe Disease Life Expectancy

It is a life threatening condition with a very low survival rate. Children suffering from this syndrome have an average lifespan of 13 months. Many children die when only 2 years old. However, those who develop the symptoms at an older age are likely to reach their early adulthood.

Krabbe Disease Pictures

Here are some images that display how this disease can affect the external appearance of a patient.

Picture 1 –  Krabbe Disease

Picture 2 – Krabbe Disease Image

Although Krabbe Disease is an incurable and fatal condition, children affected with the condition can have a relatively long life if diagnosed and treated properly at an early stage.

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