1. Canavan’s Disease
By Carissa D’Agostino

2. What is Canavan’s? Named after Myrtelle Canavan
Described disease in 1931
First female pathologist
Disease Group: Leukodystrophies
Neurological genetic disorder affects the nerve cells of the brain  deterioration of the brain
Brain can no longer receive and send messages to the body.
It is one of 50 Leukodystrophies, a disease group known for degeneration of myelin, the fatty covering used to insulate nerve fibers.
Also called: Canavan-Van Bogaert-Bertrand Disease, Spongy Degeneration of central Nervous System, Aspartoacylase deficiency, ASPA Deficiency, Aminoacylase 2 Deficiency, ACY2 Deficiency, ASP Deficiency
What is Canavan’s?

3. Cause 1933- Dr. Rueben Matalon
Discovered the gene from tissues of Canavan patients
Led to carrier screening & prenatal testing
Mutation in ASPA gene prevents breakdown of NAA Chemical imbalance with Myelin & build up destruction of Myelin & brain’s nerve cells
ASPA gene is located on Chromosome 17 at 17pter-p13
Many mutations in ASPA were found
A305E- most common in non-Jewish patients & the most ancient mutation found
E285A & Y231X- most common in Ashkenazi Jews
The gene responsible is ASPA which codes for the making of aspartoacytlase enzyme. Apastoacytlase breaks down NAA (N-acetyl-L-aspartic acid) that is found in nerve cells. NAA’s function is unclear but is probably involved in the production of myelin or “white matter”, fatty insulation to nerve cells. The build up of NAA after the ASPA mutation destroys myelin which leads to brain damage.
Cause

4. Inheritance Autosomal Recessive Affects all Ethnic backgrounds
Both parents must be carriers
Affects all Ethnic backgrounds
Mostly Ashkenazi Jews
1 in 6,400-13,500 have it
1 in 38 are carriers
General population: 1 in 300 are carriers
Matalon found congenital, infantile & late onset forms
Ashkenazi Jews are from East and Central Europe. Dr. Matalon had 70 patients with Canavan’s and only 5 were non- Jewish. Out of the Jewish patients most came from East Europe and 35 came from Saudi Arabia, where the disease is very common.
Inheritance

5. Symptoms Develop in Early Infancy (3-6 months) Gradual loss of skills
Lifespan:
Usually about 18 months
Most only have childhood- age 10
Very few reach their teens and young adulthood
Symptoms

6. Symptoms Macrocephaly Nasal regurgitation Deafness Irritability
Optic atrophy
Lack of head control
Blindness/ Poor Vision
Hypotonia, especially in the neck
Nystagmus
Delayed closure of anterior fontanelle
Reflux with vomiting
Severe intellectual disabilities
Seizures
Difficulty swallowing
Opisthotonous
Hyperreflexia
Loss of very early milestones
Joint stiffness
Decerebrate- Stiff bent arms, clenched fists, legs straight out
Delay in development
Motor loss
Heartburn
Brian Atrophy
Trouble sleeping
Demyelination
Macrocephaly- large head
Optic atrophy- tissue loss in the optic nerve of the eye
Nystagmus- rapid involuntary movements of the eye
Hypotonia- poor muscle tone
Opisthotonous-muscle spasms
Decerebrate-decorticate posture
Symptoms

7. Diagnosis Biochemical and DNA tests Increased amounts of NAA in urine
Finding known or novel mutations
95% certainty if someone is a carrier
Increased amounts of NAA in urine
Aspartoacylase deficiency in cultured skin fibroblasts
Blood Chemistry
CSF chemistry
MRI or CT
Prenatal diagnosis is difficult
CVS- Chorionic Villus Sampling
Amniocentesis
Genetic Counseling
Novel= New
CSF- Cerebral Spinal Fluid analysis
Prenatal diagnosis is difficult because of low aspartoacylase activity
CVS-placenta
Amniocentesis- fluid around fetus
Diagnosis

8. Treatment No Known Cure Treatment Based on Symptoms
From Life-extending to Comfort measures
Lithium and other drugs
Researching: Gene Therapy, Stem cells & Acetate supplement
Support Groups: Canavan Foundation & Jacob’s Cure
Drugs used to slow down the progression of the disease
Treatment

9. Summary Named after Myrtelle Canavan
A neurological disorder  affects nerve cells & causes brain deterioration
Caused by a mutation with ASPA gene found on chromosome 17 by Dr. Matalon demyelination.
Autosomal Recessive
Affects mostly Ashkenazi Jews
Symptoms develop in early infancy & lifespan is usually no longer than childhood
Diagnosis by MRI, CT, DNA testing, Prenatal testing, aspartoacylase deficiency, or increased amounts of NAA
Treatment follows patient’s symptoms because there is no known cure.
Research: Gene therapy, stem cells & acetate supplement to find more treatments
Summary

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Works Cited