Summary about Disease
Galactosylceramidase deficiency, also known as Krabbe disease or globoid cell leukodystrophy, is a rare, inherited lysosomal storage disorder caused by a deficiency of the enzyme galactosylceramidase (GALC). This enzyme is crucial for breaking down certain fats called galactolipids, primarily galactosylceramide, which is an important component of myelin, the protective sheath around nerve fibers. Without sufficient GALC, galactolipids accumulate in the brain and other tissues, leading to demyelination, nerve damage, and severe neurological problems.
Symptoms
Symptoms vary depending on the age of onset (infantile, late-infantile, juvenile, adult).
Infantile Krabbe Disease (most common): Irritability, muscle stiffness (hypertonia), feeding difficulties, developmental delay or regression, seizures, vision and hearing loss, sensitivity to stimuli, and progressive loss of motor skills.
Late-Infantile, Juvenile, and Adult Krabbe Disease: Milder and slower progression of symptoms, including walking difficulties, muscle weakness, vision problems, peripheral neuropathy, cognitive decline, and ataxia (loss of coordination).
Causes
Krabbe disease is caused by mutations in the GALC gene. This gene provides instructions for making the galactosylceramidase enzyme. Mutations in *GALC* lead to a deficiency or absence of the functional enzyme, resulting in the accumulation of galactolipids. The disease is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent).
Medicine Used
There is no cure for Krabbe disease. Treatment focuses on managing symptoms and providing supportive care.
Hematopoietic stem cell transplantation (HSCT): HSCT, particularly if performed early in the course of the disease (ideally before significant symptom onset), may slow down the progression of the disease, especially in infantile Krabbe.
Physical therapy: To maintain muscle strength and flexibility.
Occupational therapy: To assist with daily living skills.
Medications: To control seizures, muscle spasms, and pain.
Nutritional support: To address feeding difficulties.
Is Communicable
No, Krabbe disease is not communicable. It is a genetic disorder caused by inherited gene mutations, not by an infectious agent.
Precautions
Since Krabbe disease is a genetic disorder, precautions mainly involve genetic counseling and testing for at-risk families. If a couple is known to be carriers of a GALC gene mutation, they can consider:
Genetic testing: Prenatal testing or preimplantation genetic diagnosis (PGD) can determine if a fetus or embryo is affected.
Carrier screening: Testing of family members to identify other carriers.
How long does an outbreak last?
Krabbe disease is not an outbreak-related disease. It is a chronic, progressive condition. The duration of the disease varies depending on the age of onset and the severity of the enzyme deficiency. Infantile Krabbe disease is generally rapidly progressive, with a life expectancy of only a few years after diagnosis. Later-onset forms progress more slowly.
How is it diagnosed?
Diagnosis typically involves a combination of:
Clinical evaluation: Assessing symptoms and neurological findings.
Enzyme assay: Measuring galactosylceramidase (GALC) enzyme activity in blood leukocytes or cultured skin fibroblasts. Low enzyme activity is indicative of Krabbe disease.
Genetic testing: Analyzing the GALC gene for mutations.
MRI of the brain: To assess for characteristic white matter abnormalities (demyelination).
Nerve conduction studies: To assess peripheral nerve function.
Timeline of Symptoms
The timeline of symptoms varies depending on the age of onset.
Infantile Krabbe Disease: Symptoms typically appear before 6 months of age. Initial symptoms may be subtle, such as irritability and feeding difficulties. Rapid progression follows, with developmental regression, muscle stiffness, seizures, vision and hearing loss, and eventual loss of motor skills.
Late-Infantile Krabbe Disease: Symptoms may appear between 6 months and 3 years of age. Progression is slower than in infantile Krabbe.
Juvenile and Adult Krabbe Disease: Symptoms may appear in childhood, adolescence, or adulthood. The course of the disease is highly variable, but generally involves slower progression than the infantile form.
Important Considerations
Early diagnosis is crucial: Early diagnosis, particularly in infantile Krabbe disease, is important because HSCT may slow the progression of the disease if performed before significant neurological damage occurs.
Genetic counseling is essential: Genetic counseling provides information about the inheritance pattern of Krabbe disease and the risks of recurrence in families.
Supportive care is vital: Management of symptoms and supportive care are essential for improving the quality of life for individuals with Krabbe disease and their families.
Newborn screening: Some states have included Krabbe disease in newborn screening programs, which allows for earlier detection and intervention.