Leukodystrophies (Inherited White Matter Disorders)

What are Leukodystrophies?

Leukodystrophies are a group of rare, progressive genetic metabolic disorders (inborn errors of metabolism) that affect the white matter of the brain and spinal cord. Each type of leukodystrophy is caused by a specific gene abnormality that leads to a range of neurological problems. Some forms are present at birth, while others may not show symptoms until a child becomes a toddler. Early detection and early intervention are essential to give children with leukodystrophies the best chance for normal growth, development, and quality of life.

While there are more than 50 different types of leukodystrophies, the more common childhood leukodystrophies are Adrenoleukodystrophy (ALD) and Krabbe disease:

Adrenoleukodystrophy (ALD), or X-linked ALD is caused by mutations in the ABCD1 gene on the X chromosome that causes a buildup of certain fatty acids in the nervous system and adrenal glands. The condition is more common in boys, with symptoms appearing between ages 4 and 10. Symptoms include behavioral changes, poor memory, visual loss, learning disabilities, seizures, poorly articulated speech, difficulty swallowing, deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, increased skin pigmentation, and progressive dementia.  Among boys with X-linked ALD, some will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic stem cell transplant before or soon after symptom onset.  The NewYork-Presbyterian & Weill Cornell Medicine Leukodystrophy Center provides expert surveillance and treatment for patients affected by CCALD.

Krabbe disease (globoid cell leukodystrophy) is caused by mutations in the GALC gene that encodes an enzyme responsible for the breakdown of multiple lipids in the brain, resulting in a toxic accumulation of these lipids in cells throughout the nervous system. This results in progressive neurodegeneration and brain atrophy, with symptoms that include spasticity, loss of hearing and vision, seizures, weight loss, aspiration, loss of developmental milestones, and early mortality. Krabbe disease usually results in death before the age of two. The NewYork-Presbyterian & Weill Cornell Medicine Leukodystrophy Center is an open site for the GALax-c Gene Therapy Clinical Trial for patients affected by Infantile Krabbe Disease. For more information, please go to the Clinical Trials office.  [Note to web team: link to Clinical Trials page].

Other childhood leukodystrophies include:

• Aicardi-Goutieres syndrome
• Alexander disease
• Canavan disease
• Childhood ataxia and cerebral hypomyelination (CACH)/ vanishing white matter disease (VWMD)
• GM1 gangliosidosis
• Metachromatic leukodystrophy
• Mucopolysaccaridosis type III (MPS III) – Sanfilippo syndrome
• Pelizaeus-Merzbacher disease
• Pol III-Related Leukodystrophies