Genetic screening for Krabbe disease: Learning from the past and looking to the future

Abstract

In Israel, Krabbe disease is frequent in two Moslem Arab villages in the Jerusalem area. In this paper we present our experience of almost four decades with diagnosis of Krabbe disease, carrier screening and prenatal diagnosis. The screening program is well accepted by the community, and there is a clear trend towards premarital testing. The screening program and prenatal diagnosis have led to a decrease in the incidence of Krabbe disease from 1.6 per 1,000 live births to 0.82 per 1,000.

Lifetime risk estimators in epidemiological studies of Krabbe Disease

“…They are also critical outcome measures for public health interventions. See the report of Macarov et al 27 for an example in which epidemiological measures are used to document the success of a screening program for Krabbe disease implemented in a community in Israel. In the current review, we describe various problems that limit the utility of many other previously published epidemiological estimates of Krabbe disease rates in larger populations.…”

“…Three studies estimated lifetime risk for other disease categories, but also provided sufficient information to estimate it for Krabbe disease 22 - 24 . Three studies estimated this proportion for isolated sub-populations within Israel and will not be reviewed further 25 - 27 . Several book chapters provided epidemiological estimates without describing the methods used for estimation 28 - 31 …”

Ethical and Policy Issues in Newborn Screening of Children for Neurologic and Developmental Disorders

“…36,37 Over 4 decades, the rate of Krabbe disease has fallen from 1.6 per 1000 live births to 0.82 per 1000 in this region. 38 This is probably not replicable in other areas because of the large number of mutations that have been found, although once a microarray for neuromuscular disease carrier status is developed, the analysis may change.…”

Krabbe Disease in the Arab World

“…3 The carrier rate was estimated to be one in six. 31 Macarov et al 55 presented the results of a fourdecade investigation of prenatal diagnosis and carrier screening for KD in two Muslim Arab villages, which are part of the Jerusalem municipality. These authors found that half of the Arab women did not believe in the effectiveness of prenatal diagnosis, which is consistent with the findings of Jaber et al, 56 wherein half of the women expressed doubts regarding the accuracy of prenatal diagnosis.…”

“…This practice has led to a reduction in the incidence of KD from 1.6/ 1,000 to 0.82/1,000 live births. 55 A recent study by Foss et al 57 reviewed the proper use of epidemiological measures to document the success of the genetic screening programs for KD in the two Arab Muslim villages. They provided an interpretation for the previous risk estimates reported by Zlotogora et al 32 and Macarov et al 55 to determine the life-risk estimator for these populations.…”