Death rates in the U.S. due to Krabbe disease and related leukodystrophy and lysosomal storage diseases

Abstract

Leukodystrophies (LD) and lysosomal storage disorders (LSD) have generated increased interest recently as targets for newborn screening programs. Accurate epidemiological benchmarks are needed in the U.S. Age-specific mortality rates were estimated for Krabbe disease (KD) and nine related disorders. U.S. mortality records with E75.2 cause of death code during 1999-2004 were collected from 11 open record states. All E75.2 deaths in the United States were distributed into specific disease type based on proportions observed in these states. Yearly population sizes were obtained from the CDC and averaged. Mortality rates (per million individuals per year) by age group for the specific diseases were (for <5 or ≥5 years): Pelizaeus-Merzbacher (0.037/0.033); sudanophilic leukodystrophy (SLD) (0.037/0.004); Canavan (0.037/0.011), Alexander (0.147/0.022); Krabbe (0.994/0.007); metachromatic leukodystrophy (0.331/0.135); Fabry (0.000/0.124); Gaucher (0.221/0.073); Niemann-Pick (NP) (0.442/0.088); multiple sulfatase (0.000/0.004). This is the first report of mortality rates for the LD/LSD diseases in the U.S. Approximated birth prevalence rate for the early infantile Krabbe phenotype (onset 0-6 months) was based on the <5 year old mortality rate of one early infantile case per 244,000 births, which matches the 1 in 250,000 observed in the NYS newborn screening program as of 2011. It should be noted however that the NYS calculation refers only to the early infantile phenotype and does not include the majority of babies identified in the program with low GALC and two mutations who have remained clinically normal. It is presumed that most, if not all, will develop later onset forms of the disease, but this is by no means certain.

Lifetime risk estimators in epidemiological studies of Krabbe Disease

“…Age-specific mortality rates have been published for the United States, 38 but have not been published for any other country. Although not treated at length in the current paper, mortality rates provide useful information and should be similarly estimated and published for countries outside of the United States.…”

“…It was found that mortality in children less than five years of age (0.994 deaths per year per million children) was greater than mortality in older individuals (0.007 deaths per year per million individuals). Barczykowski et al 38 also showed that the yearly mortality rate in children less than 5 y of age due to Krabbe disease is a good approximation to the incidence rate of the early infantile form of Krabbe disease.…”

“…Only one study 38 aimed to measure age-specific mortality rates. Using national and state death certificates in the United States, the number of deaths of individuals with Krabbe disease was estimated for the years 1999–2004.…”

A microglial hypothesis of globoid cell leukodystrophy pathology

“…GLD is an orphan disease, and it is often grouped together with other infrequent diseases of CNS white matter referred to as leukodystrophies . In the general population, GLD has a prevalence of 1:250,000 among live births (Barczykowski et al, ). This infantile form of the disease is fatal, with death before the age of 2 years.…”

Krabbe Disease

“…However, a recent study using death rates estimates the birth prevalence at about 1-250,000. 24 The birth rate for Krabbe disease is higher among certain ethnic groups. As the birth demographics change in the United States population, the incidence of Krabbe disease may change.…”