Israel Medical Association Journal

Objective: To assess the ability of TREC and KREC counts to identify patients with combined T and B cell immunodeficiency in a pilot study in Israel.

Methods: We studied seven children born in Israel during the years 2010–2011 and later diagnosed with SCID, and an additional patient with pure B cell immunodeficiency. TREC and KREC in peripheral blood upon diagnosis and in their neonatal Guthrie cards were analyzed using real-time quantitative polymerase chain reaction, as were Guthrie cards with dried blood spots from healthy newborns and from normal and SCID-like controls.

Results: The first features suggestive of SCID presented at age 3.1 ± 2.4 months in all patients. Yet, the diagnosis was made 4.1 ± 2.9 months later. Their TREC were undetectable or significantly low at their clinical diagnosis and in their originally stored Guthrie cards, irrespective of the amount of their circulating T cells. KREC were undetectable in six SCID patients who displayed B cell lymphopenia in addition to T cell lymphopenia. KREC were also undetectable in one patient with pure B cell immunodeficiency.

Conclusions: TREC and KREC quantification are useful screening tests for severe T and B cell immunodeficiency. Implementation of these tests is highly important especially in countries such as Israel where a high frequency of consanguinity is known to exist. 

Background: Genetic screening tests for cystic fibrosis (CF), fragile X (FRAX) and spinal muscular atrophy (SMA) have been offered to the entire Arab population of Israel in the last few years. Since 2008, screening for CF is provided free of charge, but for FRAX and SMA the screening is privately funded with partial coverage by complementary health insurance programs.

Objectives: To assess the compliance of Arab couples for genetic screening tests, and the factors that affect their decisions.

Methods: We analyzed compliance for genetic screening tests at the Emek Medical Center Genetic Institute, and in outreach clinics in four Arab villages. We enquired about the reasons individuals gave for deciding not to undergo testing. We also assessed the compliance of these individuals for the triple test (a screening test for Down syndrome).

Results: Of the 167 individuals included in our study, 24 (14%) decided not to be tested at all. Of the 143 (86%) who decided to be tested, 109 were tested for CF only (65%) and 34 (20%) for SMA and FRAX (as well as CF). The compliance rate for the triple test was 87%. Technical reasons, mainly financial issues, were the most significant factor for not undergoing all three tests.

Conclusions: The compliance of the Arab community for genetic testing for SMA and FRAX is extremely low. We believe that this low utilization of screening is due to economic reasons, especially when a complementary health plan has not been acquired, and largely reflects the perception that these tests are less important since they are privately funded.
 

Background: Ultrasound examination of the fetus enables diagnosis of many major malformations during pregnancy, providing the possibility to consider interruption of the pregnancy. As a result, in many cases the incidence of malformations at birth does not represent their true incidence.

Objectives: To determine the impact of prenatal diagnosis and termination of pregnancy on the relative incidence of malformations at birth among Jews and Muslim Arabs in Israel.

Methods: Data on selected major malformations in 2000–2003 were collected from the two large central databases of the Ministry of Health and the Central Bureau of Statistics which contain information regarding births, stillbirths and terminations of pregnancies.

Results: For many malformations the total incidence was much higher than the incidence at birth. For almost all of the malformations studied, the total incidence was higher in Muslims than in Jews and the differences were further accentuated among the liveborn because of the differences in the rate of pregnancy terminations.

Conclusions: In order to detect possible influences of environmental or genetic factors on major malformations in Israel, it is critical to look at data including pregnancy terminations, stillbirths and live births.

Background: The national program for the prevention of Down syndrome includes screening (using the triple test) and invasive diagnostic tests in women at risk for a Down syndrome pregnancy. However, despite the program, the majority of Down syndrome infants are born alive (approximately 1/1000 live births)

Objectives: To determine whether the relatively high incidence of Down syndrome at birth in Israel is the result of failure of the preventive program or due to informed choices of the mothers.

Methods: We conducted a retrospective study using the national registry of Down syndrome for the years 1997 and 2004, according to the mothers' religion and place of residence and the reasons for prenatal diagnosis.

Results: Most of the babies affected with Down syndrome are born in religious or traditional conservative communities where termination of pregnancy is usually not an option.

Conclusions: In a pluralistic society like Israel with its diverse communities and dissimilar religious backgrounds and traditions, the different attitudes concerning utilization of the national program should be respected. It is necessary to tailor different approaches and solutions for the various ethnic and religious communities according to their need.
 

Background: Open neural tube defects are among the most common severely disabling birth defects. Secondary prevention by early diagnosis during pregnancy and abortion of affected fetuses lead to a marked reduction of NTD[1] incidence at birth. For primary prevention of these defects, in August 2000 the Israel Ministry of Health issued guidelines recommending a daily 0.4 mg folic acid supplement for all women in their childbearing years with special emphasis on the 3 months preceding conception and the first trimester of pregnancy.

Objectives: To compare the epidemiologic characteristics of NTD in Israel before and after the guidelines for folic acid supplementation.

Methods: A national registry of NTD was begun in 1999. Since the Ministry of Health published the recommendation for folic acid supplementation in mid-2000, the years 1999–2000 represent the status prior to the recommendation and the years 2002–2004 the status after.

Results: A marked decline in the rate of spina bifida was observed in the last 3 years (from 4.9 to 2.7 per 10,000 live births among Jews and 9.5 to 6.2 among Arabs and Druze). There was no apparent reduction for anencephaly.

Conclusions: Following the Ministry of Health guidelines on folic acid supplementation for women in the reproductive age, a marked reduction in the rates of NTD was observed. In light of this apparent success, continuous efforts should be made to increase the percentage of women taking the supplementation and, especially, to introduce folic acid fortification.

Background: Infant mortality in Israel is twofold higher among non-Jews than Jews.

Objectives: To determine the impact of congenital malformations and Mendelian diseases on infant mortality.

Methods: We compared the causes of infant mortality in a 4 year period among Jewish and non-Jewish Israeli citizens. Classification was done by analyzing all the death reports according to whether or not the child had any known major malformation, Mendelian disease and/or a syndrome, irrespective of the immediate cause of death.

Results: The infant mortality among non-Jews was double that among Jews (9 versus 4.4 per 1,000 live births). The rate of children with malformations/genetic syndromes was 3.1 times higher among non-Jews than among Jews (2.94 vs. 1.25 per 1,000 live births). The most significant difference was in the rate of Mendelian diseases, which were 8.3 times more frequent in non-Jewish children (0.16 vs. 1.33 per 1,000 live births respectively). A Mendelian disease was diagnosed in almost 15% of the non-Jewish infants and in less than 5% of the Jewish infants.

Conclusions: The most striking difference between the Jewish and non-Jewish infants was the incidence of congenital malformations and Mendelian diseases parallel to the differences in the consanguinity rates between the two populations.
 

Background: Open neural tube defects are among the most common malformations of the fetus. Secondary prevention by early diagnosis during pregnancy and abortion of affected fetuses result in a marked reduction of NTD incidence at birth. The dramatic effect of folic acid for primary prevention of these defects led to recommendations for folic acid supplementation in women of reproductive age.

Objective: To describe the epidemiologic features of NTD in Israel in 1999±2000.

Methods: A national registry of NTD was begun in 1999. During the years 1999±2000, a non-syndromic NTD was diagnosed in at least 394 pregnancies (166 anencephaly, 166 spina bifida, 43 encephalo-cele, and 19 with other types of NTD). The religious-ethnic affiliation was known in 392 cases (209 Jews and 183 non-Jews).

Results: Despite a marked decline in the rate of NTD at birth in the last few decades, the total rates during pregnancy did not change significantly, demonstrating that the changes were secondary to termination of affected pregnancies. At birth, NTD were almost four times more frequent among non-Jews (3.6 per 10,000 live births for anencephaly and 5.9 for spina bifida) than among Jews (anencephaly 1/10,000 live births, spina bifida 1.4/10,000 live births). The complete data of the registry showed an approximately twofold difference in the overall rates during pregnancy between Jews (anencephaly 5.3, spina bifida 4.6, total 11/10,000 live births) and non-Jews (anencephaly 8.8, spina bifida 10.3, total 22.3/10,000 live births). The registry demon-strated that the significant differences in NTD incidence observed at birth between Jews and non-Jews are secondary to a combined effect of a higher frequency of the malformations among non-Jews and a lower proportion of termination of affected pregnancies among non-Jews.

Conclusions: The data presented here will serve as a basis for evaluating the impact of the Ministry of Health recommendations for folic acid supplementation on the incidence of NTD.
 

The screening program in Israel for Tay-Sachs disease has proven very successful, giving Jewish couples a choice not to have affected children. The technology of carrier detection is now possible in several other severe genetic diseases that are relatively frequent among Jews. Due to the current confusion, a policy is needed to determine how the TSD screening program should be continued in the Israeli Jewish population. We propose that such a screening program include only mutations agreed by consensus as causing a disease severe enough to warrant the possibility of therapeutic abortion. We also propose that general screening include only mutations that are relatively frequent, taking into account the carrier frequencies in the Israeli Jewish population.