Clinical Neurosciences Center

Understanding Leukodystrophies in Children

Utah researchers find higher than expected incidence; outline improved diagnostic methods for inherited leukodystrophies

SALT LAKE CITY: Researchers at the University of Utah have improved methods for identifying and diagnosing a group of diseases known as inherited leukodystrophies, opening doors for earlier treatment and intervention.  Their research was released this week in the journal Neurology.

Leukodystrophy refers to a group of disorders characterized by progressive degeneration of the white matter of the brain.  The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers.  Myelin, from which the white matter of the brain takes its color, is a complex substance made up of at least ten different molecules.  Each of the inherited leukodystrophies is the result of a defect in the gene that controls the production or metabolism of one of the component molecules of myelin.

Patients with leukodystrophy are severely affected by their disease: almost half required feeding tubes, and just over half were ever able to walk independently. This severity of neurologic impairment is reflected in high health care costs. The total cohort cost over a time period of 10.5 years was $14 million, with an average per year per patient cost of $22,579, not including outpatient therapies.

Joshua Bonkowsky, MD, a pediatric neurologist at the University of Utah stated that the results released today showed an incidence of leukodystrophy of 1 in 7,663 live births, significantly higher than previously estimated.  Dr. Bonkowsky also noted that the finding of high mortality rates in the first 2 years of life for children with leukodystrophies underscores the necessity of improved methods for diagnosis.  “This is especially important because currently half of the patients are not diagnosed,” Dr Bonkowsky continued.  “Further, because some treatments (such as bone marrow therapy) are most successful when initiated in the presymptomatic stage, early diagnosis is critical.”

Another important finding was to identify the most common forms of the disease that were present in the study cohort, suggesting a logical testing strategy. “Patients presenting with a leukodystrophy should be tested for metachromatic leukodystrophy and mitochondrial disease, and male patients should be tested for Pelizaeus-Merzbacher disease and X-linked adrenoleukodystrophy,” Bonkowsky stated. “These 4 disease categories account for 25.4% of the inherited leukodystrophies in our cohort.”

An unprecedented finding was that epilepsy as more widespread than is commonly expected for white matter disease (49% of patients).  Further, the onset of seizures was at a relatively young age (average 4.0 years, with the largest proportion of cases presenting before age 2 years), which is only 1 year after the average age at presentation.   




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