This fact sheet provides information about Leukodystrophies, a group of disorders that involve the destruction of myelin. This is a fatty covering used by the body to insulate nerve fibres.

 

Leukodystrophies

 

Leukodystrophies are a group of disorders that involve the destruction of myelin. Myelin is a fatty covering that is used by the body to insulate nerve fibres and helps to promote rapid transmission of nerve impulses through the nervous system. If there is a problem with the myelin, as is the case in leukodystrophies, nerve impulses can be disrupted, leading to an impairment of the nervous system.

Diagnosis

Diagnosis will depend on the type of leukodystrophy, and often will need a number of specialists to be involved, including neurologists, and geneticists. The diagnostic methods vary between types, some of these include:

  •  Physical examination
  •  Blood testing
  •  Urine testing
  •  Genetic testing
  •  MRI
  •  Nerve conduction testing

 

Signs and Symptoms

  •   Vary by disease (see below)

 

Treatment

No specific therapy is currently available to treat these disorders. Management is generally supportive and includes a multitude of medical participants including physicians, occupational therapists, physiotherapists and many more.

Types specific to section 24 of the NDIS Act

Alexander disease [infantile and neonatal forms]

Alexander disease is a rare disorder of the nervous system caused by a mutation of the GFAP gene. The GFAP gene provides the instructions for the formation of a protein called glial fibrillary acidic protein, which provides support and strength to the cells in the nervous system. Alexander disease is characterised by destruction of the myelin sheath, and abnormal protein deposits known as Rosenthal fibres. Most cases of Alexander disease begin before the age of two.

Frequency

The prevalence of Alexander disease is largely unknown. Since the disease was first described in 1949, only approximately 500 cases have been reported.

Signs and Symptoms

Neonatal

  •  Occurs in the first month of life
  •  Severe intellectual disability
  •  Severe developmental delay
  •  Build-up of fluid on the brain (hydrocephalus)
  •  Seizures
  •  Usually fatal within the first few weeks to years of life

 

Infantile

  •  Enlarged head size
  •  Seizures
  •  Stiffness of the arms and/or legs
  •  Intellectual disability
  •  Developmental delay
  •  Failure to thrive
  •  Speech problems
  •  Usually fatal within the first few years of life

 

References: 

Alexander Disease (2019). Retrieved from https://ghr.nlm.nih.gov/condition/alexander-disease#genes

Alexander Disease (2019). Retrieved from https://rarediseases.org/rare-diseases/alexander-disease/ 

Alexander Disease (2019). Retrieved from https://rarediseases.info.nih.gov/diseases/5774/alexander-disease

Alexander Disease (2019). Retrieved from https://www.uptodate.com/contents/alexander-disease#H1

Canavan disease

Canavan disease is a progressive neurological disorder that becomes apparent during infancy. The disease is caused by a problem with the ASPA gene, which provides instructions for the production of an enzyme called aspartoacylase.

Under normal circumstances, this enzyme breaks down a substance called N-acetyl-L-aspartic acid, which is found predominately in neurons in the brain.

Ultimately, mutations in this gene damages the ability of the neurons in the brain to send and receive messages.

Children generally will show signs in the first three to nine months of life, and do not live past the age of 10.

Frequency

Canavan disease is most common in people of Ashkenazi Jewish heritage, with an estimated incidence of approximately 1 in 6, 400- 13, 500 people. Incidence in other populations is unknown.

Signs and Symptoms

  •  Rapidly increasing head circumference
  •  Lack of head control
  •  Reduction in visual responsiveness
  •  Developmental delay- delay in turning over, delay in sitting unassisted
  •  Weak muscles (hypotonia)
  •  Seizures
  •  Feeding and swallowing difficulty

Krabbe disease [globoid cell leukodystrophy]

Krabbe disease is an inherited neurological disorder that results from a defect in the GALC gene which provides instructions for the production of an enzyme called galactosylceramidase.

Galactosylceramidase, under normal circumstances, is responsible for breaking down a type of fat called galactolipids, which form part of the myelin in neurons. A reduction in the activity of this enzyme leads to build-up in certain cells, forming globoid cells and ultimately to the demyelination (damage to the protective coat) of neurons.

Signs of the disease generally become apparent during the first year of life, and people with the infantile form rarely survive beyond the age of two.

Frequency

Krabbe disease affects approximately 1 in 100, 000 people.

Signs and Symptoms

  •  Irritability
  •  Muscle weakness
  •  Feeding difficulty
  •  Episodes of fever with no specific sign of infection
  •  Stiff posture
  •  Intellectual disability
  •  Developmental delay

As the disease progresses

  •  Difficulty moving, chewing, swallowing, and breathing
  •  Vision loss
  •  Seizure
  •  Nerve pain in the hands and feet

 

Types

  •   Infantile [begins between 3-6 months of age]
  •   Late infantile [begins between 6 months – 3 years of age]
  •   Juvenile [begins between 3 to 8 years of age]
  •   Adult onset [begins after 8 years of age]

 

Pelizaeus-Merzbacher disease [connatal form]

Pelizaeus-Merzbacher disease is an inherited condition involving the nervous system. It is divided into two forms classic and connatal (present from birth).

Pelizaeus-Merzbacher disease is caused by a mutation in the PLP1 gene which is responsible for making proteolipid protein 1 and another protein called DM20.

Both these proteins are found within the cell membrane of the nerve cells, and make up the majority of myelin.

In Pelizaeus-Merzbacher disease the accumulation of excess protein leads to swelling and breakdown of nerve fibres.

Frequency

The prevalence of Pelizaeus-Merzbacher disease is approximately 1 case in 200, 000 to 500, 000. The condition affects mainly males, and rarely females.

Signs and symptoms

  •  Difficulty with feeding
  •  Poor weight gain
  •  Developmental delay
  •  High-pitched breathing (stridor)
  •  Nystagmus
  •  Progressive speech difficulty
  •  Problems with balance (ataxia)
  •  Weak muscles (hypotonia)
  •  Seizures
  •  Contractures that affect movement (people with Pelizaeus-               

Merzbacher disease connatal form are never able to walk)

References:

Alexander Disease (2019). Retrieved from https://ghr.nlm.nih.gov/condition/alexander-disease#genes

Alexander Disease (2019). Retrieved from https://rarediseases.org/rare-diseases/alexander-disease/ 

Alexander Disease (2019). Retrieved from https://rarediseases.info.nih.gov/diseases/5774/alexander-disease

Alexander Disease (2019). Retrieved from https://www.uptodate.com/contents/alexander-disease#H1

Canavan Disease (2019). Retrieved from https://ghr.nlm.nih.gov/condition/canavan-disease# 

Canavan Disease (2019). Retrieved from https://rarediseases.info.nih.gov/diseases/5984/canavan-disease  

Krabbe Disease (2019). Retrieved from https://ghr.nlm.nih.gov/condition/krabbe-disease#statistics

Pelizaeus-Merzbacher Disease (2019). Retrieved from https://ghr.nlm.nih.gov/condition/pelizaeus-merzbacher-disease#statistics

Pelizaeus-Merzbacher Disease (2019). Retrieved from https://rarediseases.info.nih.gov/diseases/4265/pelizaeus-merzbacher-disease