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J. Ekstein, B. Rubin, Sylvia Anderson, D. Weinstein, G. Bach, D. Abeliovich, Michael Webb, N. Risch (2004)
Mutation frequencies for glycogen storage disease Ia in the Ashkenazi Jewish populationAmerican Journal of Medical Genetics Part A, 129A
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Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I)European Journal of Pediatrics, 161
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The article in this issue on allelic homogeneity of GSD1a in the Ashkenazi Jewish population convincingly establishes a facile DNA diagnostic approach to screening for this disorder [Ekstein et al., 2004 ]. Although the authors do not specify what particular type of screening they envision, presumably they mean preconception screening of the Dor Yeshorim population that will be used to avoid the marriage of carrier couples and avert the conception of affected children. The authors suggest that there are strong arguments in favor of the establishment of screening and cite the incidence of mental retardation and other complications that have been reported in a survey of children with GSD1a to bolster their argument [Rake et al., 2002 ]. It should be emphasized that the frequencies of these complications are derived from a survey of children who had heterogeneous mutations and who were diagnosed after developing symptoms. The progression of this disease among a cohort of children diagnosed prenatally or through newborn screening has not been determined. Liver and kidney transplantation ameliorate but do not eliminate symptoms of the disorder [Labrune, 2002 ], and we do not know if gene therapy or enzyme therapy may be useful for this disease. Ekstein et al. [ 2004 ] do not discuss whether homozygotes for the R83C mutation have a course that is distinct from typical GSD1a. GSD1a is in a gray zone of metabolic diseases whose effects can be ameliorated, but not completely treated with aggressive therapy. Clearly, GSD1a is milder than Tay–Sachs disease [Gravel et al., 2001 ] or typical metachomatic leukodystrophy [von Figura et al., 2001 ], two diseases with uniform progression to early death. Just as clearly, it is much worse than disorders like GSD type 6 [Chen, 2001 ] or medium chain acyl coA dehydrogenase deficiency [Roe and Ding, 2001 ], where treatment of symptoms early in life can obviate essentially all serious consequences of the disease. The suggestion that screening for GSD1a in the Ashkenazi population should be implemented must be examined carefully. As we contemplate more disorders for various modes of screening in various populations, we will need to be acutely cognizant of the many factors at play in there decisions. The severity of‐ and treatment options for, the disorders under consideration will need to be integrated with knowledge about the efficacy of the available treatment(s) and the social and moral views of the populations that we consider for screening. Indeed, there are profoundly different factors that should be analyzed depending on whether one is intending to perform preconception (or in this case premarital) carrier screening, prenatal screening, or newborn screening. One issue that should be considered is that of surrendered autonomy. The Dor Yeshorim program solicits testing from individuals who then inquire through the program to determine if they are compatible with a proposed mate. If both are a carrier for one of the diseases covered by the testing, they are told that they are “incompatible.” The actual test results are not returned to individuals, nor are they told the particular disorder for which they are both carriers. Within the Dor Yeshorim community, there appears to be a consensus that surrendering the autonomy of personal decision‐making regarding carrier screening is appropriate for the avoidance of lethal disorders. When this model is applied to treatable disorders (such as cystic fibrosis and GSD1a) the advantages and disadvantages of the screening program should be re‐examined. The targeted population needs to be informed about the conditions that are part of this screening program and participate in the decision about implementation of that screening. For treatable disorders, some persons may prefer to marry the mate of their choice rather than avoid the risk of occurrence of one of these disorders. One wonders as well how far this screening program will proceed into the spectrum of successively milder disorders. The results in the Ekstein et al. [ 2004 ] study clearly show that the screening technique would be simple, but the questions surrounding implementation of such a technique are complex. Just because the DNA assay is easy does not mean the screening should be done. The opinions expressed here are those of the author and do not represent any policies or positions of the institutions to which he is affiliated.
American Journal of Medical Genetics Part A – Wiley
Published: Jun 30, 2006
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