Israel Medical Association Journal

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

Background: The prevalence of Group A streptococcus (GAS) carriage among adults is studied less than in children. The variability of reported carriage rates is considerably large and differs among diverse geographic areas and populations.

Objectives: To evaluate the prevalence of GAS carriage among adults in Israel.

Methods: In this prospective study, conducted in a large healthcare maintenance organization in Israel, we obtained pharyngeal cultures from adults attending the clinic without upper respiratory tract complaints or fever. Patient data included sex, age, number of children, and religious sectors.

Results: From May to December 2022, eight family physicians collected a total of 172 throat swabs (86% response rate). The median age was 37 years (range 18–65); 72.7% were females, 22.7% were ultra-Orthodox Jewish, and 69.2% had children. The prevalence of GAS carriage was 6.98%, 95% confidence interval (95%CI) 3.7%–11.9%. GAS carriers were younger (31.7 vs. 39.3 years, P = 0.046), and the majority were ultra-Orthodox Jews (58.3% vs. 20%, P = 0.006). All GAS carriers were from lower socioeconomic status. When assessing risk factors for GAS carriage using multivariate analysis, only being an ultra-Orthodox Jew was positively related to GAS carriage (adjusted odds ratio 5.6, 95%CI 1.67–18.8).

Conclusion: Being an ultra-Orthodox Jew was the single variable associated with a GAS carriage, which may be related to having many children at home and living in overcrowded areas. Primary care physicians in Israel should recognize this situation when examining patients with sore throats, mainly ultra-Orthodox Jews.

Background: Preoperative radiotherapy is standard treatment for rectal cancer and is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU[1] derivative, given daily during a course of radiotherapy mimics the effect of continuous-infusion 5FU.

Objectives: To determine the maximum tolerated dose of oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer, and assess tumor response.

Methods: In this phase 1 trial, 16 patients aged 42–79 years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant with the first 4 weeks of radiotherapy. Surgery was scheduled for 4–6 weeks after completion of radiotherapy. The surgical procedure was determined by the surgeon at the time of surgery.

Results: No grade III toxicity was seen at 200 mg/m²/day UFT. Of eight patients who received 240 mg/m²/day UFT, one developed grade IV diarrhea; of four patients who received 270 mg/m²/day UFT, one was hospitalized with grade IV diarrhea and leukopenic fever and died during hospitalization. Of the 15 evaluable patients, 9 had pathologic tumor down-staging including 4 patients with complete response. Only one patient required a colostomy.
Conclusions: The MTD[2] of UFT together with leucovorin and preoperative radiotherapy for rectal cancer is 240 mg/m². The major toxicity was diarrhea. Down-staging was noted in 60% of patients, allowing sphincter-preserving surgery even in patients with low tumors.