Lutfi Jaber

The Impact of Consanguinity Worldwide

Consanguineous marriages have been practiced for hundreds of years in many parts of the world. The rate of congenital malformations among the offspring is 2.5 times higher than that among the offspring of unrelated parents, mainly due to the expression of autosomal-recessive disorders, and hospitalization for these reasons causes a major financial burden. An increase in sterility and in the rates of abortion, stillbirths, perinatal losses and neonatal deaths has been reported by some authors but not by others. It is generally accepted that the advantages of consanguinity outweigh the disadvantages; however, strategies for reducing the burden require a unique approach as discussed in this article.

Trends in the frequencies of consanguineous marriages in the Israeli Arab community

To assess the trends in the frequency of consanguineous marriages in the Israeli Arab population in the last 40 years, we conducted a two‐part study. For the first part, we re‐analyzed data from a nationwide study carried out in 1992, and for the second part, we undertook a new survey in 1998 in four locations: Taibe, Tira, Kalansuwa and Kafr Bara. Data regarding the frequency of consanguineous marriage in these four locations for the years 1961–1985 was extracted from the original survey, and for the years 1986–1998, from new questionnaires. 
The frequency of consanguineous marriage was highest in the period 1961–1965 (50.6%), but by the period 1981–1985 it had decreased to 40.6%. Over the whole time span of the 1992 study, a significant decrease was observed between the periods 1961–1975 and 1976–1985 (p<0.0001). 
In the four‐location study, there was a significant decrease in the frequency of consanguineous marriage from 52.9% in the period 1961–1970 to 32.8% in the period 1991–1998 (p=0.0006). We conclude that the custom of consanguineous marriage in the studied population is still extremely high, and preventive measures should be taken to decrease its frequency and associated complications.

Evidence for complex nuclear inheritance in a pedigree with nonsyndromic deafness due to a homoplasmic mitochondrial mutation

The relationship between mitochondrial genotype and clinical phenotype is complicated in most instances by the heteroplasmic nature of pathogenic mitochondrial mutations. We have previously shown that maternally inherited hearing loss in a large Arab-Israeli kindred is due to the homoplasmic A1555G mutation in the mitochondrial 12S ribosomal RNA gene [Prezant et al., 1993: Nat Genet 4:289-294]. Family members with this mutation have phenotypes ranging from profound hearing loss to completely normal hearing, and we have shown that there is genetic and biochemical evidence for nuclear gene involvement in this family [Bu et al., 1993: Genet Epidemiol 9:27-44; Guan et al., 1996: Hum Mol Genet 5:963-971]. To identify such a nuclear locus, two candidate genes were excluded through linkage analysis and sequencing, and a genome-wide linkage search in family members who all have the identical homoplasmic mitochondrial mutation, but differ in their hearing status, was performed. In two stages a total of 560 polymorphic genetic markers was genotyped, and the data were analyzed under model-dependent and model-free assumptions. No chromosomal region was identified as a major contributor to the phenotypic expression of the mitochondrial mutation. Thus, in this simplified paradigm of a homoplasmic mitochondrial mutation in a single kindred who all live in the similar environment of a small village, the penetrance of the mitochondrial mutation appears to depend on the interaction of multiple nuclear genes.

Dactinomycin Potentiation of Radiation Pneumonitis: a Forgotten Interaction

No mention of dactinomycin potentiation of pulmonary radiation was found in a review of the literature of the past 12 years. Before that, this complication was well described and investigators had calculated that dactinomycin increased the toxic effect of lung radiation by a factor of 1.3 and reduced the radiation tolerance of the lung by at least 20%. An example of such a toxic effect is described in the treatment of a 7-year-old girl with lung metastases from Ewings sarcoma. The chemotherapy protocol followed contained cyclophosphamide, vincristine, dactinomycin, adriamycin, cisplatinum, VP16, and radiotherapy. The treatment was associated with fatal pulmonary fibrosis following the reintroduction of dactinomycin after radiotherapy. Our experience suggests that there is clinical significance to this complication in sarcoma therapy when dactinomycin-containing protocols are used with radiation in the treatment of pulmonary metastases.

Childhood malignant thymoma: clinical, therapeutic, and immunohistochemical considerations.

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.

Continuous decrease of consanguineous marriages among Arabs in Israel.

To describe the trend in the rate of consanguineous marriages among the Israeli Arab population and to identify factors associated with this custom shift in recent years.

Facial clefting in an Arab town in Israel

To study the prevalence of cleft palate and cleft lip with or without cleft palate in an Israeli Arab town, questionnaires were sent to the parents of 1375 pupils in grades 1 and 2 in all seven primary schools in the town of Taibe, and 1281 responded. The information requested included data about siblings and members of the parental generation to give a total of 16 174, and the presence of consanguinity and history of exposure to medication, radiation, smoking or alcohol during pregnancy.

Iron polymaltose versus ferrous gluconate in the prevention of iron deficiency anemia of infancy.

We prospectively compared the efficacy and safety of iron deficiency anemia prophylaxis with iron gluconate (IG) or iron polymaltose complex (IPC) in healthy infants attending a community pediatric center. Participants were randomly assigned to receive one of the test drugs from age 4 to 6 months to age 12 months. Parents/guardians were given extensive information on iron-rich diets and anemia prevention. Main outcome measures were blood levels of hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width, and serum iron, ferritin, and transferrin, in addition to adverse effects. One hundred five children completed the study: 53 in the IG group and 52 in the IPC group Mean hemoglobin levels at study end were significantly higher in the IG group (12.04±0.09 g/dL vs. 11.68±0.11, P<0.014). A hemoglobin level <11 g/dL was detected in 3 infants of the IG group, and in 10 infants of the IPC group (P<0.04). Adverse effects (spitting, vomiting, diarrhea, constipation, discolored teeth) were significantly more common in the IG group (47% vs. 25%, P>0.025). In conclusion, both oral IG and IPC prevent iron deficiency anemia in infants. Iron gluconate seems to be more effective but less tolerable.

Changing Epidemiology of Methylphenidate Prescriptions in the Community: A Multifactorial Model:

Objective: To examine dispensing patterns of methylphenidate (MPH) to determine how socioeconomic status (SES), ethnocultural affiliation, and gender affect the medical treatment of ADHD. Method: We reviewed MPH prescription records for year 2011 of children aged 6 to 18, from regional pharmacies serving homogeneous neighborhoods. Results: MPH prescriptions showed an increase in prevalence from 4.2% to 7.5% in the years 2007 to 2011, respectively. Jewish children were four times more likely to be prescribed MPH than Arab children, with significant discrepancies along SES and gender lines (p < .001). Higher SES and male gender were associated with greater use of MPH. General pediatric prescription rates of MPH in all communities increased by 85%, compared with year 2007 statistics (p < .001). Conclusion: Prescription patterns for MPH in children reflect diagnostic patterns of ADHD that appear to be heavily influenced by additive factors of SES, cultural attitudes, and gender. Dispensing data provide valuable information for targeting underserved groups and defining potential areas of abuse.

Infectious Episodes Following Diphtheria-Pertussis-Tetanus Vaccination A Preliminary Observation in Infants

Eighty two infants, aged 2-12 months, were prospectively studied for infectious episodes following diphtheria-pertussis-tetanus (DPT) immunization. The occurrence of infectious episodes during the month following vaccination was compared to that during the month prior to its administration. The 3 days following vaccination were not included. In comparison to the month prior to immunization, during the month following there were significantly more infants with fever (6.1% vs. 24.4%, p < 0.001), with diarrhea (7.3% vs. 23.1%, p < 0.005), and with cough (37.7% vs. 52.4% p N.S.). After the first month of the study, there was an increase in morbidity in the region, so we reevaluated those cases who had been seen during the latter 3 months. The same trend was found: in the month following immunization there were significantly more infants with fever (5.3% vs. 25%, p < 0.005), with diarrhea (10.5% vs. 28%, p < 0.02), and with cough (26% vs. 54%, p < 0.01). There was no correlation between the incidence of these episodes and the age at vaccination. In addition to reactive fever during the first 3 days following DPT immunization, an increase in infectious episodes seems to occur in infants during the month following administration of this vaccine.