Kawarabi: Administrative Structuring of a Multicenter Research Collaborative to Study Kawasaki Disease in the Arab Countries.

Kawasaki disease (KD), the leading cause of acquired heart disease in children in developed countries, merits conducting detailed studies in Arab countries. We introduce Kawarabi, as a multicenter research collaborative effort dedicated to improving diagnosis, care, and outcome of children and adults with KD in the Arab world. During the COVID-19 pandemic, there emerged a new multisystem inflammatory syndrome in children; a disease similar to KD. This highlighted the challenges that Arab physicians face in diagnosing and managing children with KD and KD-like illnesses. Kawarabi brings together experts in North America and Arab nations to study this family of diseases in a not-for-profit, voluntary scientific collaborative setting. Bylaws addressing the vision, objectives, structure, and governance of Kawarabi were established, and vetted by the 45 organizing members in 2021. An initial scientific publication showed evidence of a decreased level of awareness of the disease in the general population, as well as the lack of access to resources available for physicians caring for children with KD in Arab countries. Kawarabi has since held several educational webinars and an inaugural yearly meeting. The groundwork for future initiatives targeted at increasing awareness and understanding of the management and the long-term outcomes of children with KD in the region was established. Data on KD in the Arab world are lacking. Kawarabi is a multicenter research collaborative organization that has the unique resources, diversified ethnic makeup, and energy, to accomplish significant advances in our understanding and management of KD and its variants.

Characteristics and etiologies of short stature in children: Experience of an endocrine clinic in a Tunisian tertiary care hospital.

BACKGROUND: Short stature is a common reason for referral to pediatric endocrinology clinics. It may be a manifestation of a pathological condition requiring early treatment. The aim of this study was to describe the characteristics and etiologies of short stature among children referred to the pediatric endocrinology clinic of the main pediatric tertiary care center in Tunisia. METHODS: Retrospective and descriptive study in the endocrinology unit of children referred for short stature between January 2012 and December 2016. Data on the patients' medical history, physical findings, laboratory tests, bone age and chromosomal analysis were collected. RESULTS: 470 children (266 males and 204 females) were referred during that period. 214 (45.5%) had normal height, and 80.8% of them were referred by general practitioners. The other 256 children (54.5%) had a confirmed short stature (mean age :7.2 years, mean height: -2.77 SDS). Endocrinological causes were the most common(43% GHD, 4% hypothyroidism) followed by intrauterine growth retardation IUGR (24%), genetic syndromes (8.4%), chronic pediatric diseases (7.8%), skeletal dysplasia (6.2%), normal variant of short stature (5%), and psychosocial deprivation (1.2%). Among non-endocrine causes, Turner syndrome was the most common genetic syndrome (4.4%), achondroplasia the main skeletal dysplasia (4%) and celiac disease the main chronic disease (3.4%). CONCLUSIONS: ST is largely overestimated in our country. Therefore, it is important to insist on adequate measurement and analysis of growth parameters to avoid unnecessary investigations. GHD and IUGR were the most common causes. Celiac disease, though frequent in Tunisia, is not a common cause of short stature.

Congenital hypothyroidism presenting with reversible renal impairment: an under-recognised problem?

BACKGROUND: Hypothyroidism with impairment of renal function and raised creatinine phosphokinase (CPK) is described in adults and children with acquired hypothyroidism, but not in congenital hypothyroidism. CASE PRESENTATION: A male infant born at term weighing 3390 g was seen aged 2 months with prolonged jaundice. Examination showed somnolence, umbilical hernia, enlarged fontanelles and lower limb edema; length 55 cm (-1.5 SD), weight 5.4 kg (-0.13 SD). Biochemistry showed fT4 < 1 pmol/L, TSH = 1044.36 µUI/mL, creatinine 77 µmol/L(normal <35 µmol/L), estimated glomerular filtration rate (GFR) 26 ml/min/1.73 m2, CPK 3952.5 IU/L (normal<400 IU/L). Ultrasound showed no thyroid tissue in the neck. In view of the renal impairment, peritoneal dialysis was initially contemplated but postponed and the child received levothyroxine 10 µg/kg/day. Two months later thyroid function tests, CPK and renal function had all normalized with creatinine 19 µmol/L and GFR 116 ml/min/1.73m2. DISCUSSION: Reversible renal impairment is attributable to severe congenital hypothyroidism causing decreased myocardial contractility and cardiac output and to a direct effect on the kidneys. Thyroid function should be checked in infants with renal impairment of unknown cause. Cautious fluid management is indicated in hypothyroid infants. Hypothyroidism may also be associated with elevated serum CPK levels but resolves with thyroxin therapy.

A Founder Effect of c.257 + 2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients.

Chronic granulomatous disease (CGD) is the prototypic functional neutrophil disorder caused by genetic defects in one of the five genes encoding the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits of phagocytes. Mutations causing the most prevalent form of CGD in western populations are located in the X-linked-CYBB gene. The four remaining autosomal recessive (AR) forms collectively account for one-third of CGD cases. We investigated the clinical and molecular features of eleven patients with CGD from 6 consanguineous families, originating from contiguous regions in the west of Tunisia. The patients' clinical phenotype is characterized by a high incidence of mycobacterial infections. Five out of the eleven patients died despite treatment arguing in favor of a severe clinical form of CGD. These findings correlated with the absence of functional p67phox protein as well as the absence of residual reactive oxygen intermediates (ROI) production. Genetic analysis showed the presence, in all patients, of a unique mutation (c.257 + 2T > C) in NCF2 gene predicted to affect RNA splicing. Segregating analysis using nine polymorphic markers overlapping the NCF2 gene revealed a common haplotype spanning 4.1 Mb. The founder event responsible for this mutation was estimated to have arisen approximately 175 years ago. These findings will facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families.

Central system nervous tuberculosis in infants.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

[Chronic granulomatous disease in childhood]. / La maladie granulomateuse chronique de l'enfant.

Chronic granulomatous disease (GCD) of childhood is a rare inherited immunodeficiency. It is characterized clinically by the occurrence of severe and recurrent uncontrollable infections, which often lead to death in early childhood. The underlying biologic anomaly is a defective microbicidal capacity of phagocytosis with abnormal oxidative response during phagocytosis. Histologically, the GCD is characterized by a spectrum of histopathological features in a wide range of tissue specimens, often demonstrating features of active chronic inflammation, with or without non-caseating granuloma formation. The presence of numerous pigmented macrophages in association with such an inflammation should raise suspicion of the diagnosis. We report a case of a GCD in an 11-year-old boy and study the anatomoclinic features of this rare entity.

Etiology and outcome of bronchiectasis in children: a study of 41 patients.

BACKGROUND: Bronchiectasis remains an important cause of chronic suppurative lung disease in the developing world. The aim of this study is to describe the epidemiological characteristics, clinical features, underlying aetiologies and outcome of bronchiectasis in the paediatric hospital of Tunis. METHODS: A retrospective study of 41 children with bronchiectasis was conducted between January 1994 and December 2006. Diagnosis was made in patients with clinical suspicion of bronchiectasis associated with abnormalities on chest X ray (n=37) and/or on high resolution computed tomography (HRCT) (n=36). RESULTS: Mean age at diagnosis was 5 years 9 months; (range: 6 months-14 years). Persistent cough and bronchorrhea were the most common symptoms. Fourteen patients (34%) had dyspnoea on first presentation, 11 of them (26.8%) had chest deformation and/or finger clubbing. Haemoptysis was noted in only two cases. Mean time to diagnosis from symptom onset was 2.7 years (range: 2 months-4 years). The underlying aetiologies were identified in 52% of patients. Cystic fibrosis (17%), previous pneumonic illness (9.7%), primary ciliary dyskinesia (9.7%) and immunodeficiency (9.7%) were the most common causes. After a mean follow-up of 6.6 years, the annual lower respiratory infection rate decreased from 7.2 +/- 3 to 3.1 +/- 2.6 (p<0.05), Twenty one point nine per cent of patients had chronic respiratory failure and five patients required surgery. CONCLUSIONS: Delays diagnosis of bronchiectasis remains important in our country. Congenital and indeterminate aetiologies are the most common forms. Prognosis is poor with a high prevalence of chronic respiratory failure.