Canavan disease is rare genetic neurological disorder characterized by the spongy degeneration of the white matter in the brain. Affected infants may appear normal at birth, but usually develop symptoms between 3-6 months of age. Symptoms may include an abnormally large head (macrocephaly), lack of head control, severely diminished muscle tone resulting in “floppiness,” and delays in reaching developmental milestones such as independent sitting and walking. [rx]Most affected children develop life-threatening complications by 10 years of age. Canavan disease occurs because of mutations in the aspartoacylase (ASPA) gene that affects the breakdown (metabolism) of the N-acetylaspartic acid (NNA). It is inherited as an autosomal recessive condition.[rx]
Canavan disease belongs to a group of disorders known as the leukodystrophies. The leukodystrophies are a group of rare, progressive, metabolic, genetic disorders that can affect the brain, spinal cord and often the nerves outside the central nervous system (peripheral nerves). [rx]Each type of leukodystrophy is caused by an abnormality affecting a specific gene that results in abnormal development of one of at least 10 different chemicals that make up the white matter of the brain. The white matter is tissue composed of nerve fibers. Many of these nerve fibers are covered by a collection of fats (lipids) and proteins known as myelin. Myelin, which collectively may be referred to as the myelin sheath, protects the nerve fibers, acts as an insulator and increases the speed of transmission of nerve signals. Each type of leukodystrophy affects a different part of the myelin sheath, leading a range of different neurological problems.[rx]
Canavan Disease is a rare genetic disorder that affects the brain’s development. It’s important to understand the different aspects of this condition, including its types, causes, symptoms, diagnostic tests, treatments, and available drugs. In this article, we will simplify complex medical information to make it easily understandable to a wide audience.
Types of Canavan Disease:
- Infantile Canavan Disease:
- The most common form of the disease.
- Symptoms appear in infancy.
- Juvenile Canavan Disease:
- Less common than infantile Canavan.
- Symptoms typically appear in childhood or adolescence.
- Adult-Onset Canavan Disease:
- Rare form.
- Symptoms begin in adulthood.
Types of Canavan Disease:
- Classic Infantile Canavan Disease: This is the most severe form of Canavan Disease and typically appears in infancy, usually within the first few months of life. Infants with classic infantile Canavan Disease often show more profound symptoms and developmental delays.
- Late-Onset Canavan Disease: Late-onset Canavan Disease is a milder form of the condition, and its symptoms typically manifest later in childhood or even in adolescence. Individuals with this type may experience a slower progression of the disease and may have a higher level of cognitive functioning.
Causes of Canavan Disease:
- Genetic Mutation:
- Caused by mutations in the ASPA gene.
- These mutations disrupt the breakdown of a substance called NAA in the brain.
- Autosomal Recessive Inheritance:
- Both parents must carry a mutated ASPA gene for a child to develop Canavan Disease.
- Parents are often carriers without symptoms.
- Genetic : Canavan Disease is a genetic disorder caused by a specific mutation in the ASPA gene. This mutation disrupts the normal functioning of the ASPA enzyme, leading to the accumulation of a substance called N-acetyl-L-aspartic acid (NAA) in the brain. This buildup of NAA causes damage to the brain’s white matter.
- Autosomal Recessive Inheritance: To develop Canavan Disease, a child must inherit two copies of the mutated ASPA gene, one from each parent. If both parents carry one mutated ASPA gene and one normal gene, they are considered carriers but do not have the disease themselves.
Canavan disease is caused by disruptions or changes (mutations) to the aspartoacylase (ASPA) gene. This mutation is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.[rx]
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.[rx]
The defective gene responsible for Canavan disease has been mapped to chromosome 17 (17pter-p13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.[rx]
The ASPA contains instructions for developing (encoding) aspartoacylase, an enzyme that breaks down (metabolizes) N-acetylaspartic acid (NAA). NAA is a compound that researchers believe plays a vital role in maintaining the brain’s white matter. Deficient or inactive aspartoacylase results in the accumulation of NAA in brain tissue. The symptoms of Canavan disease result from damage to the white matter from the abnormally high levels of NAA.[rx]
Symptoms of Canavan Disease:
- Poor Head Control:
- Infants may struggle to hold their heads up.
- Lack of Developmental Milestones:
- Delayed or absent milestones like rolling over and sitting up.
- Difficulty Swallowing:
- Infants may have trouble feeding.
- Seizures:
- Seizures can occur at any age.
- Regression:
- Loss of previously acquired skills, such as babbling or smiling.
- Muscle Stiffness:
- Muscles may become rigid.
- Blindness:
- Vision loss is common in Canavan Disease.
- Hearing Impairment:
- Hearing problems may develop.
- Breathing Issues:
- Difficulty breathing and respiratory infections can occur.
- Enlarged Head:
- Head size may increase due to fluid buildup.
- Intellectual Disability:
- Profound intellectual impairment is a hallmark of the disease.
- Sleep Disturbances:
- Trouble sleeping through the night.
- Weakness:
- Muscular weakness is common.
- Paralysis:
- Some individuals may become paralyzed.
- Swallowing Difficulties:
- Trouble swallowing, leading to feeding problems.
- Loss of Motor Skills:
- A decline in motor function over time.
- Behavioral Changes:
- Changes in behavior and mood.
- Reduced Lifespan:
- Canavan Disease can shorten lifespan significantly.
Diagnostic Tests for Canavan Disease:
A diagnosis of Canavan disease may be suspected in infants with the characteristic findings of the disorder (e.g., poor head control, macrocephaly, etc.). [rx]A diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests. Such tests may include may include gas chromatography-mass spectrometry, a device that can detect elevated levels of NAA in the urine. Elevated levels of NAA can also be detected in the blood and cerebrospinal fluid (CSF). Examination of certain connective tissue cells from the skin (cultured fibroblasts) can reveal deficiency of the enzyme aspartoacylase. Aspartoacylase activity is also absent in white blood cells.[rx]
- Genetic Testing:
- Identifies mutations in the ASPA gene.
- Brain MRI:
- Detects brain abnormalities.
- NAA Levels:
- Measures NAA levels in the brain, typically elevated in Canavan Disease.
- Clinical Evaluation:
- Neurological exams and developmental assessments.
- Urine Analysis:
- Elevated NAA levels in urine may indicate the disease.
Treatment Options for Canavan Disease:
The treatment of Canavan disease is directed toward the specific symptoms that are apparent in each individual. Supportive care may alleviate some discomfort. Physical therapy and early intervention may help to improve posture and communication skills, respectively. If swallowing difficulties occur, feeding tubes may be useful to ensure proper nutrition and hydration. Seizures may be treated with anti-seizure (anti-convulsant) medications.[rx]
- Supportive Care:
- Focuses on managing symptoms and improving quality of life.
- Physical Therapy:
- Helps with mobility and muscle stiffness.
- Speech Therapy:
- Assists with communication and swallowing difficulties.
- Occupational Therapy:
- Aids in daily activities and motor skills.
- Medications:
- Seizure medications to control seizures.
- Muscle relaxants to reduce muscle stiffness.
- Feeding Tubes:
- May be necessary for individuals with severe swallowing problems.
- Respiratory Support:
- Ventilators and oxygen therapy for breathing issues.
- Clinical Trials:
- Experimental treatments in research studies.
Available Drugs for Canavan Disease:
- N-Acetylaspartate (NAA):
- Investigational treatment to supplement NAA levels in the brain.
- Antiseizure Medications:
- Medications like valproic acid to manage seizures.
- Muscle Relaxants:
- Drugs like baclofen to alleviate muscle stiffness.
- Symptomatic Relief Medications:
- Medications for pain, sleep disturbances, and other symptoms.
Conclusion:
Canavan Disease is a rare genetic disorder with different types and a range of symptoms. Early diagnosis and supportive care are crucial for individuals affected by this condition. While there is no cure, various treatments and therapies can improve the quality of life for those living with Canavan Disease. Ongoing research and clinical trials offer hope for future advancements in treatment. If you suspect someone has Canavan Disease or are a carrier, genetic counseling can provide valuable information and support.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. Thank you for giving your valuable time to read the article.
