Children and adolescents of racial or ethnic minorities, such as blacks and Hispanics, are less likely to be diagnosed with a leukodystrophy, according to a recent study.
The research, “Association of Diagnosis of Leukodystrophy With Race and Ethnicity Among Pediatric and Adolescent Patients,” was published in the journal JAMA Network Open.
Given the variable clinical presentation of leukodystrophies (rare, progressive, genetic diseases that affect the brain, spinal cord, and often peripheral nerves) and their outcomes, genetic studies may help understand issues related to their diagnosis and treatment.
So far, almost all studies of leukodystrophies were performed in the U.S. or Europe, and predominantly with patients of Caucasian ancestry. The incidence of leukodystrophies in racial/ethnic minority patient populations has been poorly studied.
So, researchers from the University of Utah School of Medicine and Intermountain Healthcare, in Salt Lake City, investigated whether there are variations in leukodystrophy diagnosis in different racial backgrounds.
“Because some leukodystrophies are treatable but require timely diagnosis…understanding ethnic and racial differences is critical for effective screening, diagnosis, and treatment,” the researchers wrote.
The team used the U.S. Children’s Hospital Associations Pediatric Health Information System database to review data from patients aged up to 18 years who had been diagnosed with either X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD), Krabbe disease, or Hurler disease, from Oct. 1, 2015, to Sep. 30, 2017.
According to the team, these four diseases were selected based on their specific genetic diagnosis: mutations in the ABCD1 gene underlie X-ALD; in ARSA they cause MLD; in GALC they lead to Krabbe disease, and; in IDUA they cause Hurler disease.
Researchers obtained adjusted prevalence estimates of leukodystrophies by taking into account the patient’s sex, insurance type, living in an urban or rural area, 2010 median household income for patient ZIP code, number of inpatient days, and age at first visit.
Among the 557 identified patients (336 males, median age of 7 years, range newborn-18 years), the most common racial groups were: white non-Hispanic (321 patients; 58% of the group); 54 were black non-Hispanic (10%); 51 white Hispanic (9%), and; nine Asian (2%).
A total of 139 patients (25%) had MLD, 111 (20%) had X-ALD, and 56 each (10%) Krabbe disease or Hurler disease.
The team found that being non-white — including black, black Hispanic, and white Hispanic backgrounds — correlated with not having a leukodystrophy diagnosis. This was observed both when leukodystrophies were tested together, and when specific diseases were considered separately.
The adjusted leukodystrophy prevalence in white non-Hispanic patients was 13.8 per 100,000 patients, compared to 7.4, 5.8, and 2.4 and 7.4 per 100,000 in white Hispanic, black non-Hispanic, and black Hispanic patients, respectively. Of note, the lower rate in non-whites was inferior to the frequency of these different races in the database.
Furthermore, researchers found similar or higher frequencies of mutations in the four leukodystrophy-associated genes in patients of Latino and African descent than in white non-Hispanics, suggesting that the lower diagnosis rates in non-whites was not due to less mutation frequency.
“Patients of racial/ethnic minorities, including those from black, black Hispanic, and white Hispanic backgrounds, were significantly less likely to be diagnosed with a leukodystrophy,” the scientists wrote.
While the reasons for this observation are still not clear, according to the researchers, this lower incidence may be due to different rates of de novo mutations (DNA alterations that occur during embryonic development), the presence of disease modifier genes, clinical symptoms specific for different racial backgrounds, misdiagnosis, and/or lack of access to specialists or to coverage for testing.
The team emphasized that the fact “patients of racial/ethnic minorities are being underdiagnosed for leukodystrophies … can result in a lack of treatment or insufficient treatment,” and that it “may reflect a more general problem in pediatric neurological and rare diseases.”
