Kamal, N. M., A. N. Sahly, B. Banaganapalli, O. M. Rashidi, P. J. Shetty, J. Y. Al-Aama, N. A. Shaik, R. Elango, and O. I. Saadah, "Whole exome sequencing identifies rare biallelic ALMS1 missense and stop gain mutations in familial Alström syndrome patients.", Saudi journal of biological sciences, vol. 27, issue 1, pp. 271-278, 2020. Abstractwhole_exome_alstrom.pdf

Alström syndrome (AS, OMIM ID 203800) is a rare childhood multiorgan disorder, which is widely studied in non-Arab ethnic patients. The clinical and molecular basis of AS and the mode of disease inheritance in consanguineous Arab populations is not well investigated. Therefore, to identify the molecular basis of AS in familial forms, the present study performed whole exome sequencing of 5 AS patients belonging to 2 different Bedouin families from Saudi Arabia. The present study identified the AS causative rare biallelic mutations in ALMS gene:T376S in exon 5 and S909* in exon 8 for family A and an R2721* in exon 10 (R2721*) for family B. ALMS1 targeted genetic sequencing of healthy population controls and family members has confirmed its extremely rare frequency and autosomal recessive mode of inheritance. The truncating mutations S909* and R2721* could cause the loss of CC domains and ALMS motif on C-terminal end of the protein and creates unstable protein, which eventually undergoes intracellular degradation. The premature protein truncating mutations described in our study may eventually provide further insight into the functional domains of the ALMS1 protein and contribute to the understanding of the phenotypic spectrum of AS. Whole exome sequencing based molecular diagnosis is expected to rule out ambiguity surrounding clinical diagnosis of suspected AS cases.

Mokhtar, W. A., L. M. Sherief, H. E. Sayed, M. M. Shehab, S. M. El Gebaly, A. M. M. Khalil, M. Sobhy, and N. M. Kamal, "Conventional intensive LED intensive phototherapy oxidative stress burden in neonatal hyperbilirubinaemia of haemolytic origin.", Paediatrics and international child health, vol. 40, issue 1, pp. 30-34, 2020. Abstractconv_led_phototherapy.pdf

: Phototherapy causes oxidative stress which is of particular importance in neonates because of the increased susceptibility of neonatal red blood cell membranes to oxidative damage.: To evaluate the oxidant/antioxidant status in neonates with haemolytic hyperbilirubinaemia before and after exposure to two different intensive phototherapy light sources.: A randomised controlled study was undertaken in 54 full-term neonates with indirect haemolytic hyperbilirubinaemia admitted to a neonatal intensive care unit in the first week of life. They were randomly divided into two equal groups. Group 1 infants were exposed to intensive conventional phototherapy (Bilisphere 360) and Group 2 were exposed to an intensive light-emitting diode (LED) phototherapy device (Bilitron bed 3600). Total serum bilirubin (TSB), total oxidative stress (TOS), total antioxidant capacity (TAC) and the oxidative stress index (OSI) were measured before and 48 hours after initiation of phototherapy.: There was a significant decrease in TSB after phototherapy in both groups ( < 0.001). The TOS and OSI were significantly increased after phototherapy in both groups ( < 0.001) but more so in Group 1 with conventional phototherapy ( = 0.05 and 0.01, respectively). TAC was significantly decreased after phototherapy in both groups ( < 0.00) but more so in Group 1 ( = 0.03).There were significant increases in the incidence of dehydration, hyperthermia and skin rash in the conventional compared with the LED phototherapy group ( = 0.02, 0.01 and 0.02, respectively). However, there was a significant increase in the incidence of hypothermia in the LED compared with the conventional phototherapy group ( = 0.001).: Both intensive conventional and LED phototherapy are equally effective in decreasing TSB, but intensive LED phototherapy is safer than intensive conventional phototherapy with regard to oxidative stress and oxidant/antioxidant imbalance. DSB: direct serum bilirubin; G6PD: glucose-6-phosphate dehydrogenase enzyme; LED: light-emitting diode; OSI: oxidative stress index; TAC: total antioxidant capacity; TOS: total oxidative stresses; TSB: total serum bilirubin.

Mostafa, M. A., N. M. Kamal, S. Eltaher, Y. Hamed, H. Abdelaziz, W. Abdelghany, E. Aser, E. Fawzy, and L. M. Sherief, "Knowledge of Neonatal Hyperbilirubinemia Among Primary Health Care Physicians: A Single-Center Experience.", Clinical medicine insights. Pediatrics, vol. 13, pp. 1179556518824375, 2019. Abstractclinical_medical_insights._nj.pdf

Background and objectives: To evaluate the knowledge of the primary health care physicians (PHCP) in Kalubia governorate, Egypt, about the causes, diagnosis, complications, and treatment of neonatal hyperbilirubinemia (NHB).

Methods: Cross-sectional survey distributed by interview to 500 physicians working in the primary health care (PHC) sector in Kalubia.

Results: Out of 500 distributed surveys, 419 (84%) PHCP completed the questionnaire. They represent 174 (90%) out of 193 PHC units and centers. About 18% were males and 82% females with mean age of 28.5 ± 5.2 years, and mean duration of work was 3.3 ± 4.4 years. All of the respondents have patients with NHB in their daily practice. The knowledge of the PHCP was good in some aspects about NHB; however, it was poor and may be even hazardous in other aspects.

Conclusions: Many areas of defects are detected in PHCP knowledge about NHB. Pre-service and continuous training of the PHCP about the diagnosis and management of NHB are essential.

Sherief, L. M., M. R. Beshir, G. M. Salem, H. S. Sherbiny, A. A. Soliman, M. A. El-Komy, M. Arafa, and N. M. Kamal, "Intrafamilial Transmission of Hepatitis C Virus Among Families of Infected Pediatric Oncology Patients.", The Pediatric infectious disease journal, vol. 38, issue 7, pp. 692-697, 2019. Abstractintrafamilial_transmission_of_hcv.pdf

BACKGROUND: Hepatitis C virus (HCV) is the most commonly encountered blood transmittable hepatitis among cancer patients. Several studies have reported clustering of HCV infections in families or household contacts of infected cases. Data about the epidemiologic aspects of intrafamilial transmission from pediatric cancer patients are scarce and still debated. We aimed to identify the magnitude of horizontal intrafamilial transmission of HCV from infected pediatric oncology patients; its prevalence, risk factors and possible routes of transmission.

METHODS: One hundred fifty-seven (86 HCV positive, 71 HCV negative) pediatric oncology patients who received treatment and follow-up at Zagazig university Hospital-Egypt and their household family contacts (751) were enrolled in this cross-sectional case-control study. Blood samples were collected from 450 relatives of HCV infected cases (group 1) and 301 household contacts of HCV-negative cases (group 2) for analysis of HCV antibodies and HCV RNA to confirm positivity. Family contacts of HCV-infected cases were interviewed, and close-ended questionnaire was completed for each participant to determine risk factors and possible routes of HCV intrafamilial transmission.

RESULTS: Significantly higher HCV prevalence and chronicity rates were documented among relatives of HCV-infected cases as compared with contacts of HCV-negative cases (12.6% and 10.6% for group 1 vs. 7% and 5.3% for group 2, respectively). Risk factors of infection were calculated by univariate and logistic regression analysis among contacts of HCV-infected cases. Female caregivers, particularly mother (OR 5.1, 95% CI: 2-13.5), contact with index cases blood, either directly without using personal protective equipment (OR 7.8, 95% CI: 2.9-23.8) or indirectly through common use of sharps (razors, scissors) (OR 8.9, 95% CI: 3.5-20.5) and nail clippers (OR 2.1, 95% CI: 1.1-5.4) and giving care to infected cases (OR 2.9, 95% CI: 1.3-16.6) represented the real predictors of intrafamilial HCV infection.

CONCLUSIONS: Intrafamilial transmission of HCV from infected children to their relatives does occur. Parenteral route is the only documented way of transmission either directly or indirectly.

Elshorbagy, H. H., N. F. Barseem, A. E. Elsadek, A. H. Al-shokary, Y. H. A. Maksoud, S. E. Abdulsamea, I. M. Talaat, H. A. Suliman, N. M. Kamal, W. E. Abdelghani, et al., "Serum Neuron-specific Enolase and S100 Calcium-binding Protein B in Pediatric Diabetic Ketoacidosis", Journal of clinical research in pediatric endocrinology, vol. 11, issue 4, pp. 374-387, 2019. Abstractjcrpe-11-374_neurone.pdf

Objective: Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) are markers of different neurological disorders. The aim was to investigate the relationship between NSE and S100B serum concentrations and the severity of diabetic ketoacidosis (DKA) in diabetic children.

Methods: Eighty children with DKA, 40 with type 1 diabetes mellitus (T1DM) without DKA and 40 healthy controls were enrolled. Severity of DKA was assessed according to blood pH and bicarbonate concentration. Serum NSE and S100B were measured in all participants. In the DKA group serum NSE and S100B were measured at three time points, at admission and at 12 hours and 24 hours after starting treatment.

Results: Children with DKA showed significantly higher serum levels of NSE at all time points compared to children with T1DM without DKA and controls (p<0.01), while serum S100B concentrations did not differ between the three cohorts. Children with T1DM but without DKA also had significantly higher serum levels of NSE (p<0.01) compared to healthy controls. Patients with low Glasgow Coma Scale score (GCSS) and those with moderate and severe DKA had significantly higher levels of NSE at all time points (p<0.01 for each) compared to patients with normal GCSS and those with mild DKA. No significant differences were found in serum S100B levels according to the severity of DKA and GCS (p>0.05). Younger age, lower GCSS, higher glucose and HbA1c, lower pH and lower serum bicarbonate were the risk factors associated with elevated NSE.

Conclusion: Serum NSE is elevated in all patients with type 1 DM and, in patients with DKA, correlates with severity of DKA. However, serum S100B concentration did not differ between T1DM with or without DKA and healthy controls.

Kamal, N. M., H. Y. Khan, Mortada HF El-Shabrawi, Ola El-Sisi, and L. M. Sherief, "Congenital chloride losing diarrhea: A single center experience in a highly consanguineous population.", Medicine, vol. 98, issue 22, pp. e15928, 2019. Abstractmedi-98-e15928_chloride.pdf

Congenital chloride losing diarrhea (CCLD) is a rare type of chronic watery diarrhea due to mutations in SLC26A3 gene leading to defective chloride-bicarbonate exchanges with the resultant loss of chloride and retention of bicarbonate.We aim to define pediatric Saudi CCLD patients' characteristics to achieve prompt diagnosis, management, follow up with good quality of life, and prevention of complications in these patients.We carried retrospective data review of demographic, clinical, laboratory, radiographic, and outcome of all pediatric patients fulfilling the criteria of CCLD over 10 years from 2004 to 2014 from a single center in Taif region, Saudi Arabia.Forty-nine patients fulfilled the criteria of CCLD from 21 families with more than one affected patient in the same family in 90% of them and positive consanguinity in 91% of the cohort. Most patients were born preterm with intrauterine growth restriction and usually neonatal intensive care unit (NICU) admissions with prematurity and its complications. Thirteen patients were discharged without diagnosis of CCLD and 3 were misdiagnosed as intestinal obstruction with unnecessary surgical intervention. Many complications do existed with renal complications being the most common with three patients received renal transplantation.Prematurity with abdominal distension and stool like urine were the commonest presentation of CCLD in Saudi children. Positive consanguinity and more than one affected sibling are present in most of our cohort.High index of suspicion by clinicians is a cornerstone for early diagnosis with subsequent favorable outcome.A multicenter national incidence study of CCLD in KSA and its genetic attributes is recommended. Premarital screening should be implemented specially for consanguineous marriage.

Halabi, A., U. Khan, K. Maazoun, and N. M. Kamal, "Abdominal mystery in a neonate.", Archives of disease in childhood. Education and practice edition, 2019. archdischild-2018-316161.full_.pdf
Yakoot, M., M. H. El-Shabrawi, M. M. AbdElgawad, A. A. Mahfouz, A. F. Khalil, N. M. Kamal, S. Helmy, A. M. Abdo, E. M. Kamal, and H. R. El-Khayat, "Effects of Dual Sofosbuvir/Daclatasvir Therapy on Weight and Linear Growth in Adolescent Patients With Chronic Hepatitis C Virus Infection", The Pediatric Infectious Disease Journal, vol. Volume Online First , issue Online First, pp. 1-13, 2018. effects_of_dual_sofosbuvir_daclatasvir_therapy_on.96506.pdf
El-Shabrawi, M. H. F., N. M. Kamal, H. R. El-Khayat, E. M. Kamal, M. M. A. H. AbdElgawad, and M. Yakoot, "A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6- to 12- year old children.", Alimentary pharmacology & therapeutics, vol. 47, issue 12, pp. 1699-1704, 2018 Jun. Abstractaliment_pharmacol_ther.pdf

BACKGROUND: No available data on the use of sofosbuvir/ledipasvir combination in treatment of hepatitis C virus (HCV) infection in children 6- to 12- year old.

AIM: To assess the safety and efficacy of sofosbuvir plus ledipasvir in children 6- to 12- year old with chronic HCV genotype 4 infection.

METHODS: This is a pilot prospective single arm observational open-label multicentre study. A total of 20 consecutive eligible chronic HCV infected children, aged from 6- to 12- years were included in this study and treated with a fixed sofosbuvir/ledipasvir combination in half the adult dose (200/45 mg) once daily for 12 weeks. Laboratory tests including virological markers were measured at baseline, 2, 4, 8 and 12 weeks (end of treatment [EOT]), and 12 weeks after end of treatment for sustained virological response 12 (SVR12).

RESULTS: The intention-to-treat (ITT) SVR12 rate was 19/20 (95%; 95% CI: 76.4%-99.1%). SVR12 was not assessed in one patient who was lost to follow-up after showing viral negativity at the EOT12. All the remaining 19 patients (100%, 95% CI: 83.18%-100%) who completed the full protocol and follow-up visits achieved SVR12 with normal liver, haematological, and renal function tests and no side effects or fatalities.

CONCLUSIONS: This pilot study demonstrated that the fixed dose sofosbuvir/ledipasvir combination could be safe and effective treatment in children 6- to 12- years with chronic hepatitis C genotype 4 infection. Our pilot results might encourage larger and multicentre studies in this age group.

El-Khayat, H., E. M. Kamal, M. Yakoot, M. A. Gawad, N. Kamal, M. E. Shabrawi, Y. Sameh, A. Haseeb, Y. Fouad, and D. Attia, "Effectiveness of 8-week sofosbuvir/ledipasvir in the adolescent chronic hepatitis C-infected patients.", European journal of gastroenterology & hepatology, 2019 Jan 22. Abstracteur_j_gastro_hep.pdf

BACKGROUND: The sustained virological response (SVR) rate for the 12-week sofosbuvir (SOF)/ledipasvir (LVD) treatment of adolescent genotype-4 patients is high. The aim of this study is to evaluate 8 versus 12-week treatment efficacy and safety in adolescent genotype-4 patients.

PATIENTS AND METHODS: In total, 157 chronic hepatitis C-infected adolescent patients (mean age 14±2 years, 62% males) were included in this study. All patients received a morning dose of SOF (400 mg)/LVD (90 mg) as a single tablet for 8 and 12 weeks. Laboratory and biochemical monitoring were performed at weeks 4 and 8, end of treatment (8/12) and 12 weeks after the end of treatment (SVR12).

RESULTS: In total, SVR12 was 98% [95% confidence interval (CI): 96-100] for all treated patients. For patients treated for 12 weeks, SVR12 was 97.6% (95% CI: 96-101) (82/84 patients), and 98.6% (95% CI: 93-101) (72/73) patients for those treated for 8 weeks. For both regimens, no serious adverse effects, treatment discontinuation or cases of death were detected. The main adverse effects for the 8-week patient group were fatigue (2.8%), headache (1.4%), nausea (1.4%) and epigastric tenderness (1.4%). For the 12-week-treated group, adverse events were epigastric tenderness (1.2%), nausea (1.2%), diarrhoea (2.4%) and rash (2.4%). Three patients were lost to follow-up: two were in the 12-week treatment group and one was in the 8-week group. All of them reached end of treatment but were lost before SVR12. No relapsers were observed in either group.

CONCLUSION: Eight weeks of treatment of SOF/LVD combination is equally effective and safe as 12 weeks in adolescent genotype-4 patients.