Summary about Disease
Galactocerebrosidase deficiency, also known as Krabbe disease or globoid cell leukodystrophy (GLD), is a rare, inherited metabolic disorder that affects the nervous system. It results from a deficiency of the enzyme galactocerebrosidase (GALC). This enzyme is necessary for the breakdown of certain fats (galactolipids), primarily galactocerebroside, in lysosomes. The buildup of these lipids, particularly psychosine, is toxic to cells, primarily the myelin-producing cells (oligodendrocytes) of the brain and spinal cord. This leads to demyelination, the destruction of the protective myelin sheath around nerve fibers, which impairs nerve function.
Symptoms
Krabbe disease has several forms, but the most common and severe is the infantile form. Symptoms vary depending on the age of onset.
Infantile Krabbe Disease:
Extreme irritability
Feeding difficulties
Muscle stiffness and spasms (hypertonia)
Developmental delay or regression
Progressive loss of motor skills
Seizures
Vision loss
Hearing loss
Fever without infection
Peripheral neuropathy (nerve damage)
Late-Onset Krabbe Disease (Juvenile or Adult):
Progressive weakness in the legs
Vision problems
Ataxia (loss of coordination)
Muscle weakness
Cognitive decline
Causes
Krabbe disease is caused by mutations in the GALC gene, which provides instructions for making the galactocerebrosidase enzyme. These mutations lead to a deficiency or complete absence of functional GALC enzyme. It is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent) to develop the disease. Individuals who inherit only one copy of the mutated gene are carriers and usually do not show symptoms.
Medicine Used
Hematopoietic Stem Cell Transplantation (HSCT): This is the primary treatment option, particularly for infantile Krabbe disease if performed before significant symptom onset. HSCT involves replacing the patient's bone marrow with healthy stem cells, ideally from a matched donor. It aims to provide a source of functional GALC-producing cells and slow or halt disease progression.
Enzyme Replacement Therapy (ERT): ERT is currently not available for Krabbe disease.
Supportive Care: Medications to manage symptoms such as seizures, muscle spasms, pain, and feeding difficulties. Physical therapy, occupational therapy, and speech therapy to maximize function and quality of life. Nutritional support to ensure adequate nutrition and hydration.
Is Communicable
No, Krabbe disease is not communicable. It is a genetic disorder caused by mutations in the GALC gene and is not infectious. It cannot be spread from person to person.
Precautions
Since Krabbe disease is a genetic disorder, there are no specific precautions to prevent it in terms of exposure or infection. However, for individuals with a family history of Krabbe disease, genetic counseling and carrier testing are recommended before planning a family. Prenatal testing (amniocentesis or chorionic villus sampling) can be performed during pregnancy to determine if the fetus is affected. After birth, newborn screening can detect Krabbe disease early, enabling timely intervention with HSCT.
How long does an outbreak last?
Krabbe disease is not an infectious disease, so the term "outbreak" does not apply. It is a chronic, progressive disorder that lasts for the duration of the affected individual's life. The rate of progression and lifespan vary depending on the form of the disease and the effectiveness of treatment. Untreated infantile Krabbe disease typically leads to death within a few years.
How is it diagnosed?
Diagnosis of Krabbe disease involves a combination of clinical evaluation, biochemical testing, and genetic testing:
Newborn Screening: Many states include Krabbe disease in their newborn screening programs. This involves measuring GALC enzyme activity in a blood sample.
Enzyme Assay: Measurement of GALC enzyme activity in leukocytes (white blood cells) or fibroblasts. Low enzyme activity indicates a possible diagnosis of Krabbe disease.
Genetic Testing: DNA sequencing of the GALC gene to identify disease-causing mutations. This confirms the diagnosis and can help determine the specific type of Krabbe disease.
MRI of the Brain: Imaging studies, such as MRI, can reveal characteristic patterns of demyelination in the brain.
Nerve Conduction Studies: Used to assess the function of peripheral nerves and detect neuropathy.
Timeline of Symptoms
Infantile Krabbe Disease:
0-6 months: Irritability, feeding difficulties, developmental delay.
6-12 months: Muscle stiffness, spasms, progressive loss of motor skills.
12-24 months: Seizures, vision loss, hearing loss.
Later stages: Progressive neurological deterioration, leading to a vegetative state and death, usually before age 2.
Late-Onset Krabbe Disease:
Variable age of onset (childhood, adolescence, or adulthood).
Initial symptoms: Progressive weakness in the legs, vision problems, ataxia.
Progressive neurological decline: Slower progression than the infantile form, but eventually leading to significant disability.
Important Considerations
Early Diagnosis is Crucial: Early diagnosis, ideally through newborn screening, is critical for successful treatment with HSCT.
HSCT is Most Effective Early: HSCT is most effective when performed before significant neurological damage has occurred.
Supportive Care is Essential: Even with HSCT, ongoing supportive care is necessary to manage symptoms and improve quality of life.
Genetic Counseling is Important: Genetic counseling is recommended for families with a history of Krabbe disease to understand the risk of recurrence and to discuss reproductive options.
Research is Ongoing: Research is ongoing to develop new and more effective treatments for Krabbe disease, including gene therapy and substrate reduction therapy.