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CANAVAN DISEASE

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CANAVAN DISEASE

Canavan disease is a rare, progressive inherited neurological disorder that causes damage to the nerve cells in the brain.

  • This disease is one of a group of genetic disorders called leukodystrophies.
  • This group of genetic disorders is rare, progressive and can affect the brain, spinal cord and often the nerve outside the central nervous system.
  • Leukodystrophies disrupt the growth or maintenance of myelin sheath, which is the covering that protects the nerves and increases the speed of transmission of nerve signals.
  • Each type of leukodystrophy affects a different section of the myelin sheath, leading to a range of different neurological disorder.
  • Canavan disease begins in infancy. Affected infants appear normal for the first few months of life, until like 3-5 months when symptoms begin to appear.
  • Life expectancy for infants with the condition usually varies but they usually develop life-threatening complications by the age of 10.

CAUSES

Canavan disease is a genetic disorder inherited in an autosomal recessive genetic pattern.

An autosomal recessive genetic pattern is one of the several ways that a trait disorder can be passed down through families

Autosomal recessive occurs when two abnormal genes are inherited, one from each parent. This means that both parents must carry the defective gene and transmit the gene to the child for the child to have the condition.

Canavan disease is caused by mutations in the ASPA gene, a gene that provides the instruction for making an enzyme called aspartoacylase. This enzyme breaks down a compound called N-acetylaspartic-acid (NAA).

The NAA is predominantly found in the neurons in the brain and is believed to play a vital role in the production of the myelin sheath.  However, recent research suggests that NAA does not have this function. This enzyme may instead be involved in the transport of water molecules out of the neurons.

Mutations in the ASPA gene reduces the function of the aspartoacylase which results in the accumulation of NAA in the brain tissue. This high level of NAA subsequently results in the progressive destruction of the myelin sheath. Over time, nerves without the myelin sheath protective covering begin to malfunction leading to a disruption in normal brain development.

SYMPTOMS

  • Delay in motor skills development such as turning over, sitting without support, and controlling head movement.
  • A usually larger head size
  • Weak or abnormal muscle tone such as stiffness or floppiness
  • Irritability
  • Seizures
  • Feeding and swallowing difficulties
Other symptoms that may develop include
  • Sleep disturbance
  • Paralysis
  • Blindness
  • Hearing loss
It should be noted that symptoms appear about 3-5 months after birth.

 

DIAGNOSIS AND TREATMENT

Diagnosis is made by carrying out thorough clinical evaluations, a detailed patient’s history, and a series of tests.

Tests may include gas chromatography-mass spectrometry that is able to detect the levels of NAA in the urine.

Elevated levels of NAA can also be detected in the blood and cerebrospinal fluids (CSF).

If both parents have known ASPA gene mutations, prenatal diagnosis is available. This involves measuring the levels of NAA in the amniotic fluids surrounding the fetus at 16-18 weeks of gestation.

TREATMENT

No cure exists for the disease and also there is no standard course of treatment.

The treatment option is systematic (directed to specific symptoms that are present in each individual) and supportive. This may include:

  • Physical therapy to improve motor skills
  • An educational program to help improve communication skills
  • Anti-epileptic drugs for seizures
  • In cases of swallowing difficulties, gastrotomy can help maintain an adequate food intake and hydration.