Single-center experience of congenital disorders of glycosylation syndrome screening in Tunisia: A retrospective study over a 15-year period (2007-2021).

BACKGROUND: We report the results gathered over 15 years of screening for congenital disorders of glycosylation syndrome (CDGS) in Tunisia according to clinical and biochemical characteristics. METHODS: Our laboratory received 1055 analysis requests from various departments and hospitals, for children with a clinical suspicion of CDGS. The screening was carried out through separation of transferrin isoforms by capillary zone electrophoresis. RESULTS: During the 15-year period, 23 patients were diagnosed with CDGS (19 patients with CDG-Ia, three patients with CDG-IIx, and one patient with CDG-X). These patients included 13 boys and 10 girls aged between 3 months and 13 years, comprising 2.18 % of the total 1055 patients screened. The incidence for CDGS was estimated to be 1:23,720 live births (4.21 per 100,000) in Tunisia. The main clinical symptoms related to clinical disease state in newborn and younger patients were psychomotor retardation (91 %), cerebellar atrophy (91 %), ataxia (61 %), strabismus (48 %), dysmorphic symptoms (52 %), retinitis pigmentosa, cataract (35 %), hypotonia (30 %), and other symptoms. CONCLUSION: In Tunisia, CDGS still remains underdiagnosed or misdiagnosed. The resemblance to other diseases, especially neurological disorders, and physicians' unawareness of the existence of these diseases are the main reasons for the underdiagnosis. In routine diagnostics, the screening for CDGS by biochemical tests is mandatory to complete the clinical diagnosis.

Nonketotic Hyperglycinemia in Tunisia. Report upon a Series of 69 Patients.

AIM: The aim of the study is to report on epidemiological, clinical, and biochemical characteristics of nonketotic hyperglycinemia (NKH) in Tunisia. METHODS: Patients diagnosed with NKH in Laboratory of Biochemistry at Rabta hospital (Tunis, Tunisia) between 1999 and 2018 were included. Plasma and cerebrospinal fluid (CSF) free amino acids were assessed by ion exchange chromatography. Diagnosis was based on family history, patient's clinical presentation and course, and increased CSF to plasma glycine ratio. RESULTS: During 20 years, 69 patients were diagnosed with NKH, with 25 patients originating from Kairouan region. Estimated incidences were 1:55,641 in Tunisia and 1:9,684 in Kairouan. Consanguinity was found for 73.9% of the patients and 42% of the families have history of infantile death due to a disease of similar clinical course than the propositus. Clinical symptoms initiated within the first week of life in 75% of the patients and within the first 3 months in 95.7% ones. The phenotype was severe in 76.8% of the patients. Main symptoms were hypotonia, feeding difficulties, coma, apnea, and seizures. Most patients died within few days to months following diagnosis. CSF to plasma glycine ratio was increased in all patients. CSF and plasma glycine levels were negatively correlated with age of disease onset and severity. CONCLUSION: NKH is quite frequent in Tunisia. Kairouan region has the highest NKH incidence rate, worldwide. However, due to lack of confirmatory enzymatic and genetic tests, NKH diagnosis was based on first-line biochemical tests. Characterization of causal mutations is needed for accurate diagnosis and prenatal diagnosis of this devastating life-threatening disease.

[Perinatal varicella: fetal and neonatal risks and management]. / La varicelle périnatale: risques et prise en charge fœtale et néonatale.

The occurrence of clinical varicella during pregnancy is rare but it may pose maternal and fetal risks. Perinatal maternal varicella may result in potentially severe neonatal varicella, especially when maternal eruptions occur between 5 days before and 2 days after delivery. We report eight cases of newborns of mothers with varicella in the peri-partum period in order to synthesize the current state of knowledge on the risk of contracting virus as well as to develop treatment protocol. We conducted a descriptive study at the Maternity and Neonatology Center, Sousse, over a period of 10 years. Eight newborns were included in the study. Prenatal diagnosis was made in 7 mothers. Only a woman developed varicella 3 days after delivery. Five newborns were symptomatic on admission. All newborns had typical varicella skin lesions, three of them had respiratory distress associated. Treatment was based on newborn isolation, local skin care and Acyclovir therapy. Patients evolution was favorable. The occurrence of varicella infection during pregnancy remains possible in the countries where vaccination is still not accessible to all. The risk of maternal and fetal complications justifies specific and well codified treatment.

Incidence of congenital heart disease in newborns after pulse oximetry screening introduction.

INTRODUCTION: Congenital heart defects are the most common congenital malformations in the newborn with an estimated incidence ranging between 6-9 ‰. In Tunisia, this incidence reaches 1.9 ‰. This can be explained by misdiagnosed cases. In fact, the diagnosis is based mainly on clinical examination which allows making the diagnosis only in 50 in 75 % of the cases. Several studies showed the interest of pulse oximetry oximeter in the screening of cyanogenic and duct dependent congenital heart diseases. The Objective of our work is to determine the incidence of congenital heart diseases screened by physical examination coupled with the measure of transcutaneous saturation Methods:  forward-looking and descriptive Study, concerning all the births of the central maternity of Sousse, during a period of 12 months. We have measured transcutaneous saturation of all the newborn children in association to routine physical, examination. This study aimed to screen congenital heart disease and then calculate their incidence. RESULTS: during the period of the study 10447 newborn children had been born in the central maternity of Sousse. Among whom, 26 had a congenital heart defect. The incidence of the neonatal cardiac malformations in our current study was found in 2.77 ‰ of alive births. It was about 1.1 ‰ of newborns in a similar study practised in 2009 (Chi2=76.2 et p<10-4). The heart disorder was diagnosed following the grip taking of the only percutaneous saturation in 5 newborn children and following the clinical examination in 21. CONCLUSION: the measure of the transcutaneous saturation in the first day of life is a little expensive and specific method for the early screening of the duct dependent cardiac malformations.

Respiratory syncytial virus infections in hospitalized infants: association between viral load, virus subgroup, and disease severity.

The relationships between host factors, virus strain, viral load, and illness severity in respiratory syncytial virus (RSV)-induced bronchiolitis are poorly defined. These relationships were evaluated prospectively in 81 previously healthy infants hospitalized with RSV bronchiolitis. Disease severity was determined by the respiratory rate, the duration of hospitalization, and whether patients during their hospitalization required pediatric intensive care unit admission or mechanical ventilation. RSV typing into subgroup A and B was obtained by RT-PCR-hybridization assay. The nasopharyngeal RSV viral loads were measured by real-time quantitative RT-PCR. Disease severity correlated significantly with the presence of risk factor (estimated gestational age < 37 weeks and/or birth weight < 2,500 g) and with chronologic age

Prenatal diagnosis of Crigler-Najjar syndrome type I by single-strand conformation polymorphism (SSCP).

Crigler-Najjar syndrome type I (CN-I) is a rare and severe inherited disorder of bilirubin metabolism, caused by the total deficiency of bilirubin-UDP-glucuronosyltransferase (UGT) activity. Enzymatic diagnosis cannot be performed in chorionic villi or amniocytes as UGT is not active in these tissues. The cloning of the UGT1 gene and the identification of disease-causing mutations have led to the possibility of performing DNA-based diagnosis. Here we report DNA-based prenatal diagnosis of CN-I in two Tunisian families in whom CN-I patients were diagnosed. As we had previously shown that CN-I was, in Tunisia, associated with homozygosity for the Q357R mutation within the UGT1 gene, we were able to detect this mutation in both families and to show that it was easily recognized by single-strand conformation polymorphism (SSCP) analysis. In both cases, SSCP analysis of fetal DNA showed that the fetus was heterozygous for the Q357R mutation. In one family, the pregnancy was carried to term and a healthy baby was born, whereas, in the other family, the pregnancy is still continuing. Thus the prenatal diagnosis of CN-I is possible, provided disease-causing mutations have been identified. SSCP analysis of DNA prepared either from amniocytes or from chorionic villi is a simple, reliable and fast method for prenatal diagnosis.