Canavan disease

Июль 21, 2022

Содержание

2. What is Canavan disease It is an autosomal recessive degenerative disorder that causes progressive damage to
3. Symptoms Symptoms of the most common form of Canavan disease typically appear in early infancy usually
4. Inheritance Canavan disease is inherited in an autosomal recessive fashion. When both parents are carriers, the
5. Diagnosis The diagnosis of neonatal/infantile Canavan disease relies on demonstration of very high concentration of N-acetylaspartic
6. Causation of the disease Canavan disease is caused by a defective ASPA gene which is responsible
7. Treatment No cure for Canavan disease is known, nor is there a standard course of treatment.
8. Treatment Also, an experimental treatment uses lithium citrate. When a person has Canavan disease, his or
9. Prognosis The more common and serious version of Canavan disease typically results in death or development
10. Prevalence Although Canavan disease may occur in any ethnic group, it mostly affects people of Eastern
11. History Canavan disease was first described in 1931 by Myrtelle Canavan. In 1931, she co-wrote a
12. Research Research involving triacetin supplementation has shown promise in a rat model. Triacetin, which can be
13. Research Acetate supplementation using triacetin is meant to provide the missing acetate so brain development can
14. Research The virus, a modified version of adeno-associated virus, is designed to replace the aspartoacylase enzyme.
15. Case Study A 15-month old boy, the second child born out of a non-consanguineous marriage, presented
16. Case Study – MRI - MRS (MRI) of the brain T2 axial image revealed marked symmetrical
17. Case Study – MRI - MRS
18. Images of Kids with canavan disease
19. Questions 1. canavan disease is an autosomal ______ degenerative disorder. 2. Canavan disease relies on demonstration
21. Скачать презентацию

Слайд 2

What is Canavan disease
It is an autosomal recessive 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.
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.

Слайд 3

Symptoms
Symptoms of the most common form of Canavan disease typically appear

in early infancy usually between the first three to six months of age.
Canavan disease then progresses rapidly from that stage, with typical cases involving intellectual disability, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone and poor head control.
Paralysis, blindness, or seizures may also occur.

Слайд 4

Inheritance
Canavan disease is inherited in an autosomal recessive fashion. When both

parents are carriers, the chance of having an affected child is 25%.

Слайд 5

Diagnosis
The diagnosis of neonatal/infantile Canavan disease relies on demonstration of very

high concentration of N-acetylaspartic acid (NAA) in the urine. In mild/juvenile Canavan disease, NAA may only be slightly elevated; thus, the diagnosis relies on molecular genetic testing of ASPA, the gene encoding the enzyme aspartoacylase.

Слайд 6

Causation of the disease
Canavan disease is 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

Слайд 7

Treatment
No cure for Canavan disease is known, nor is there a

standard course of treatment. Treatment is symptomatic and supportive. Physical therapy may help improve motor skills, and educational programs may help improve communication skills.
Seizures are treated with antiepileptic drugs and gastrostomy is used to help maintain adequate food intake and hydration when swallowing difficulties exist.

Слайд 8

Treatment
Also, an experimental treatment uses lithium citrate. When a person has Canavan

disease, his or her levels of N-acetyl aspartate are chronically elevated. The lithium citrate has proven in a rat genetic model of Canavan disease to be able to significantly decrease levels of N-acetyl aspartate.

Слайд 9

Prognosis
The more common and serious version of Canavan disease typically results

in death or development of life-threatening conditions by the age of ten, though life expectancy is variable, and is highly dependent on specific circumstances. On the other hand, the milder variants of the disorder seem not to have any effect on lifespan.

Слайд 10

Prevalence
Although Canavan disease may occur in any ethnic group, it mostly

affects people of Eastern European Jewish ancestry with about one in 40 (2.5%) individuals of Eastern European Jewish ancestry being a carrier.

Слайд 11

History
Canavan disease was first described in 1931 by Myrtelle Canavan. In 1931, she

co-wrote a paper discussing the case of a child who had died at 16 months old and whose brain had a spongy white section.
Canavan was the first to identify this degenerative disorder of the central nervous system, which was later named "Canavan disease"

Слайд 12

Research
Research involving triacetin supplementation has shown promise in a rat model. Triacetin, which

can be enzymatically cleaved to form acetate, enters the brain more readily than the negatively charged acetate.
The defective enzyme in Canavan disease, aspartoacylase, converts N-acetylaspartate into aspartate and acetate. Mutations in the gene for aspartoacylase prevent the breakdown of N-acetylaspartate, and reduce brain acetate availability during brain development.

Слайд 13

Research
Acetate supplementation using triacetin is meant to provide the missing acetate

so brain development can continue normally.
A team of researchers headed by Paola Leone at the University of Medicine and Dentistry of New Jersey, has tried a procedure involving the insertion of six catheters into the brain that deliver a solution containing 600 to 900 billion engineered virus particles.

Слайд 14

Research
The virus, a modified version of adeno-associated virus, is designed to replace

the aspartoacylase enzyme. Children treated with this procedure to date have shown marked improvements, including the growth of myelin, with decreased levels of the N-acetyl-aspartate toxin.
Researchers at the University of Toledo and Atomwise discovered the first drug-like inhibitors of N-acetyltransferase.

Слайд 15

Case Study
A 15-month old boy, the second child born out of

a non-consanguineous marriage, presented with a history of delayed attainment of milestones. At 15 months of age, the child had no head control. There was only social smile, and the child could only speak monosyllables.

Слайд 16

Case Study – MRI - MRS
(MRI) of the brain T2 axial

image revealed marked symmetrical hyperintensity of cerebral white matter involving the subcortical arcuate fibres.
(MRS) from the left parietal white matter showed N-acetyl-aspartate (NAA) peak with normal creatine and choline peaks, consistent with the diagnosis of Canavan disease.

Слайд 17

Case Study – MRI - MRS

Слайд 18

Images of Kids with canavan disease

Слайд 19

Questions
1. canavan disease is an autosomal ______ degenerative disorder.
2. Canavan disease relies

on demonstration of very high concentration of what in the urine ?
3. what is the cure for this disease?

Canavan disease

Содержание

What is Canavan diseaseIt is an autosomal recessive degenerative disorder that causes progressive

SymptomsSymptoms of the most common form of Canavan disease typically appear

InheritanceCanavan disease is inherited in an autosomal recessive fashion. When both

DiagnosisThe diagnosis of neonatal/infantile Canavan disease relies on demonstration of very

Causation of the diseaseCanavan disease is caused by a defective ASPA gene which

Treatment No cure for Canavan disease is known, nor is there a

Treatment Also, an experimental treatment uses lithium citrate. When a person has Canavan

Prognosis The more common and serious version of Canavan disease typically results

Prevalence Although Canavan disease may occur in any ethnic group, it mostly

History Canavan disease was first described in 1931 by Myrtelle Canavan. In 1931, she

Research Research involving triacetin supplementation has shown promise in a rat model. Triacetin, which

ResearchAcetate supplementation using triacetin is meant to provide the missing acetate

ResearchThe virus, a modified version of adeno-associated virus, is designed to replace

Case StudyA 15-month old boy, the second child born out of

Case Study – MRI - MRS(MRI) of the brain T2 axial