Basic info in one place, source links included (source links will open a new tab outside of the course).
- Name: Canavan Disease.
- May also be referenced as: ASPA deficiency, aspartoacylase deficiency, Canavan-Van Bogaert-Bertrand disease, Van Bogaert-Bertrand syndrome
- Variants:
- Neonatal/Infantile Canavan disease is much more common and severe, with symptoms appearing between 3-6 months of age.
- Juvenile Canavan disease is much less serious, with milder symptoms appearing later in life. Juvenlie Canavan disease doesn’t appear to significantly impact lifespan, and is often undiagnosed as its main manifestations are minor speech and motor skill development delays.
- Lifespan:
- Death or major life-threatening conditions by age 10 in most cases of Neonatal/Infantile Canavan disease, but is dependent on circumstances and can vary significantly in rare cases.
- Description: Canavan disease is an autosomalrecessive degenerative disorder that causes progressive damage to nerve cells in the brain, and is one of the most common degenerative cerebral diseases of infancy. It is caused by a deficiency of the enzyme aminoacylase 2, and is one of a group of genetic diseases referred to as leukodystrophies. It is characterized by degeneration of myelin in the phospholipid layer insulating the axon of a neuron and is associated with a gene located on human chromosome 17.
- Symptoms appear after 3-6 months of age, and include:
- Extremely poor head control
- Macrocephaly (abnormally large head)
- Hypotonia (severely diminished muscle tone), characterized by “floppiness”
- Apathy (general unresponsiveness)
- Lethargy or irritability
- Additional symptoms may include:
- Dysphagia (difficulty swallowing), often resulting in feeding difficulties
- Delays in reaching developmental milestones
- Intellectual disability
- Paralysis, blindness, or seizures
- Diagnosis:
- Diagnosis generally occurs at a caretakers recommendation upon observing characteristic symptoms in infants, and is generally confirmed by thorough clinical evaluation, patient and family history, and specialized tests including a gas chromatography-mass spectrometry test for elevated levels of NAA in urine, blood, or spinal fluid.
- A prenatal diagnosis is also available (if both parents have known ASPA gene mutations) by chorionic villus sampling (CVS) by removing a sample of placental cells at 10-12 weeks gestation.
- Affected Populations:
- Evenly distributed by gender, and occurs in all ethnic groups, but with greater frequency in those with Eastern European Jewish/Ashkenazi Jewish descent.
- 1 in 40-58 people of Ashkenazi descent is a carrier of the recessive gene
- 1 in each 6400-13,456 children born of Ashkenazi parents will have Canavan disease.
- The carrier frequency in other populations is not known, and tends to be lower.
- The overall frequency and incidence of the disease in the general population is unknown.
- Evenly distributed by gender, and occurs in all ethnic groups, but with greater frequency in those with Eastern European Jewish/Ashkenazi Jewish descent.
- Pathophysiology:
- Canavan disease is inherited in an autosomal recessive fashion. When both parents are carriers, the chance of having an affected child is 25%.
- Caused by a defective ASPA gene which is responsible for the production of the enzyme aspartoacylase. Decreased aspartoacylase activity prevents the normal breakdown of N-acetyl aspartate, wherein the accumulation of N-acetylaspartate, or lack of its further metabolism interferes with growth of the myelin sheath of the nerve fibers of the brain. The myelin sheath is the fatty covering that surrounds nerve cells and acts as an insulator, allowing for efficient transmission of nerve impulses.
Key Resources for Canavan Disease (and the sources for much of the information in this course, full citations at the end.