Spontaneous Hemopericardium Complicated by Tamponade in a Child With Moderate Hemophilia A: Case-Based Review.

Hemophilia A is the most common severe innate bleeding disorder. It is an X-linked recessive inherited bleeding disorder characterized by a qualitative and/or quantitative deficiency of factor VIII. The clinical manifestation of this disease is hemorrhaging that can affect every organ, in particular joints (hemarthrosis) and muscles (hematoma). Some serious but rare hemorrhages can be life-threatening, in particular hemorrhage of the central nervous system and hemopericardium. We report a rare case of spontaneous hemopericardium complicated by tamponade in a child with moderate hemophilia A treated with Factor VIII replacement infusion and pericardial drainage, with a favorable outcome. To our knowledge, this is the second case described in the literature of spontaneous hemopericardium occurring in a child with hemophilia A. Our case suggests that a dose of 50 IU/kg/8 h of factor VIII maintained for up to one day after removal of the pericardial drain seems to be sufficient to ensure correct hemostasis, though further evidence is needed to confirm this impression.

Acute Flaccid Myelitis in a Pediatric Patient With Coronavirus Disease 2019.

The etiology of acute flaccid myelitis (AFM) has yet to be determined. Viral link has been suggested, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated AFM has not been reported in children. We describe a three-year-old boy, with AFM associated with coronavirus disease 2019 (COVID-19) infection. In the era of COVID-19 pandemic, patients with AFM should be tested for SARS-CoV-2.

Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT).

OBJECTIVES: Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls. METHODS: Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments. RESULTS: We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4 %) with mosaicism in 37(20 %). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3 %), from birth-2 years in 14 (8 %)with lymphoedema (8)and dysmorphic features (9),2-12 years in 53 (35.5 %) including 35 with short stature, 13-18 years in 43(28.8 %) with short stature(28) and delayed puberty(14) and 35(23.5 %) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8 %), renal in 22 (19.6 %). A total of 56 girls (32 %) had proven gonadal dysgenesis and 13 (7 %) had otological problems. Parental height was available in 71 girls (40 %) of whom 59 were below the lower end of parental target range (LTR) (83 %). CONCLUSIONS: This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years' time.

Allergie aux protéines du lait de vache chez un nourrisson sous allaitement maternel exclusif.

INTRODUCTION: L'allergie aux protéines du lait de vache (APLV) est l'allergie alimentaire la plus fréquente au cours des premières années de vie. Elle est souvent associée à l'introduction des préparations à base de lait de vache et constitue une maladie rare chez les nourrissons allaités. OBJECTIF: Rapporter le cas d'une APLV chez un nourrisson sous allaitement maternel exclusif. Observation médicale. Un nourrisson âgé de 3 mois a été reçu avec une histoire de diarrhée chronique. La mère nie toute introduction de lait artificiel et le nourrisson est exclusivement nourri au sein. La concentration d'anticorps IgE spécifiques du lait de vache était en faveur de l'APLV. En interrogeant à nouveau la mère, elle souligne la notion de consommation d'une grande quantité de produits laitiers. Leur éviction était associée à un développement normal du nourrisson sans problèmes intestinaux. CONCLUSION: L'APLV peut se développer chez les nourrissons exclusivement allaités au sein. Exclure le lait de vache de l'alimentation de la mère est le seul remède quand elle veut encore allaiter.

High-fidelity simulation versus video-based learning in the management of pediatric septic shock: a pilot study.

High-fidelity simulation (HFS) and video-based learning (VBL) promote competence in acute care in a realistic and safe environment. These two modalities have not been compared in pediatric emergency situations. Interns rotating in the pediatric department were randomized for the two educational methods. The delivered learning subject was septic shock in children. The level of knowledge was measured before intervention, immediately after intervention (post-test 1) and 1 week later (post-test 2). Knowledge test scores improved significantly following intervention in both VBL study group and HFS study group (71.5 ± 13.2 [39.0-88.0], p < 0.001 and 80.1 ± 10.3 [57.4-94.5], p < 0.001, respectively). The improvement was significantly higher in HFS study group (p = 0.04). There was a non-significant drop in the retention score evaluated by the post-test 2 in the two groups compared to the post-test 1 score (66.9 ± 15.4 [31.5-86.1], p = 0.17 and 78.8 ± 12.4 [56.0-100.0], p = 0.72 in the VBL and HFS study groups, respectively). The retention score was significantly higher in the HFS group (p = 0.04).Conclusion: High-fidelity simulation and video-based training are both effective educational methods in teaching pediatric emergencies for interns. HFS appears to be superior in enhancing short-term retention. What is Known: • High-fidelity simulation is an effective educational tool to improve learners' knowledge and skills. • Video-based learning is an effective teaching tool in terms of short-term knowledge acquisition. What is New: • High-fidelity simulation is more effective in terms of short-term knowledge and generated more satisfaction than educational video learning.

Swept-source OCT findings in shaken baby syndrome: case report.

BACKGROUND: Our purpose was to document the swept source optical coherence tomography (SSOCT) findings in a patient with Shaken baby syndrome (SBS). CASE PRESENTATION: SSOCT was obtained without sedation in a six-month-old girl with bilateral multilayered retinal hemorrhages due to SBS. It documented vitreoretinal interface abnormalities, including internal limiting membrane (ILM) detachment with retinal traction, in association with other specific changes in the inner and outer retinal layers. Six weeks later, retinal hemorrhages had substantially resolved, and there was optic disc pallor. OCT showed ILM reattachment with release of retinal traction and the development of severe diffuse retinal atrophy involving the fovea. CONCLUSIONS: SS OCT can provide useful information in SBS, revealing a wide variety of vitreoretinal interface, inner, and outer retinal changes not detected by clinical examination. It also may have a prognostic value over follow-up.

Host-Range Shift Between Emerging P[8]-4 Rotavirus and Common P[8] and P[4] Strains.

In Tunisia, we observed that rotavirus P[8]-3 and P[4] strains in young children with gastroenteritis associate with secretor histo-blood group phenotype. In contrast, the emerging P[8]-4 strain, representing 10% of cases, was exclusively found in nonsecretor patients. Unlike VP8* from P[8]-3 and P[4] strains, the P[8]-4 VP8* protein attached to glycans from saliva samples regardless of the donor's secretor status. Interestingly, a high frequency of FUT2 enzyme deficiency (nonsecretor phenotype) was observed in the population. This may allow cocirculation of P[8]-3 and P[8]-4 strains in secretor and nonsecretor children, respectively.

Paraoxonase 1 polymorphisms (L55M and Q192R) as a genetic marker of diabetic nephropathy in youth with type 1 diabetes.

INTRODUCTION: Paraoxonase 1 (PON1) polymorphisms have been largely involved in diabetes complications. The aim of the study is to evaluate the effects of PON1 polymorphisms (L55M and Q192R) on diabetic nephropathy (DN). MATERIAL AND METHODS: The study involved 116 children and adolescents with type 1 diabetes (T1D) and 91 healthy subjects. Albumin excretion rate (AER) was determined by immunoturbidimetry. PON1 activity was measured by a spectrophotometric method, and genotyping of PON1 gene was assessed by multiplex PCR followed by RFLP. RESULTS: PON1 activity was inversely correlated to AER (r = -0.245, p = 0.008). A significant decrease (p = 0.037) in PON1 activity was shown between patients with nephropathy and those without (162 [57-618] vs. 316 [37-788] IU/L, respectively). The distribution of AER was, for L55M polymorphism MM > LM > LL (p = 0.002), and for Q192R polymorphism QQ > QR > RR (p < 0.001). The opposite distribution was noted for PON 1 activity (p < 0.001). LMQQ and MMQQ haplotypes seem to increase AER (p = 0.004, p = 0.003, respectively) and to reduce PON1 activity (p = 0.011, p = 0.052, respectively) in youths with T1D. However, LLRR haplotype seems to have the opposite effect. CONCLUSIONS: This study demonstrated that PON1 polymorphisms L55M and Q192R seem to be genetic markers involved in the development of DN in T1D. (Endokrynol Pol 2017; 68 (1): 35-41).

Osteoprotegerin as a marker of cardiovascular risk in children and adolescents with type 1 diabetes.

BACKGROUND: Elevated osteoprotegerin (OPG) levels have been reported in patients with diabetes complications. We investigated whether plasma OPG levels can be used as a marker of cardiovascular risk in children and adolescents with type 1 diabetes (T1D). METHODS: Plasma blood samples were obtained from 243 subjects (143 children and adolescents with T1D and 100 healthy controls). OPG concentrations were measured by enzyme-linked immunosorbent assay (ELISA) method. All data were analyzed by using PASW statistics 18. RESULTS: A significant higher plasma OPG level was found in children with T1D compared to controls (p < 0.001). A significant increase of OPG levels has been related to the glucose level ≥ 7 mmol/L (2.44 [0.01-6.22] vs. 2.16 [0.13-6.22] pmol/L, p = 0.019), microalbuminuria ≥ 30 mg/24 h (3.71 [0.160-6.03] vs. 2.26 [0.01-6.22] pmol/L, p < 0.001), and cystatin-C ≥ 0.789 mg/L (2.64 [0.37-6.22] vs. 2.11 [0.01-5.82] pmol/L, p < 0.001). We noted a significant higher frequency of children with increased cystatin-C levels in the group with elevated plasma level of OPG compared with those with normal levels (49 vs. 18%, respectively) with an odds ratio (OR) = 4.42 [1.41-13.84] (p = 0.006). We showed a significant increase of OPG levels when the number of cardiovascular risk factors exceeds 3 (p = 0.001). CONCLUSION: OPG may be a potential biomarker of cardiovascular risk in T1D. Implementation of OPG determination in the clinical laboratory setting would be useful in order to better stratify patients and to assess the most adequate treatment.

[Is paraoxonase 1 a marker of cardiovascular risk in youth with type 1 diabetes? (Study about 109 cases)]. / La paraoxonase 1: un marqueur de risque cardiovasculaire chez les jeunes diabétiques de type 1 ? (109 cas).

OBJECTIVES: We purpose to verify if paraoxonase 1 (PON1) activity may be a marker of cardiovascular risk in a young Tunisian population with type 1 diabetes (T1D). METHODS: PON1 activity was measured by a kinetic method using paraoxon as substrate. The other parameters were determined by automated methods. RESULTS: One hundred and nine children and adolescents with T1D and 97 healthy subjects were involved in this study. PON1 activity and PON1/HDL-cholesterol ratio were significantly decreased in diabetics (303 ± 174 vs. 372 ± 180 U/L and 221 ± 139 vs. 298 ± 20 1U/mmol, P=0.006, P=0.002, respectively) compared to controls. A significant increase in total cholesterol, LDL-c and microalbuminuria was observed in diabetics compared to controls. PON1 activity was decreased by 9.5% in patients with diabetes duration ≥ 6 years, by 28.4% for those with fasting glycemia ≥ 7 mmol/L (P<0.001), by 14% in those with HbA1c ≥ 8% and by 12.3% for diabetics with dyslipidemia. PON1 activity is reduced when the number of cardiovascular risk factors increases (P<0.001). CONCLUSION: PON1 seems to be associated to cardiovascular risk markers in T1D. This result remains to be seen. Nevertheless, improving PON1 activity could be a significant target for reducing cardiovascular risk.

Can paraoxonase 1 polymorphisms (L55 M and Q192 R) protect children with type 1 diabetes against lipid abnormalities?

BACKGROUND: Only a few studies have focused on the possible modulatory role of paraoxonase 1 (PON1) polymorphisms in lipid profiles, especially in children and in adolescents with type 1 diabetes (T1D). OBJECTIVE: We propose to study the association between PON1 polymorphisms (PON1-55 and PON1-192) and a lipid profile in a young Tunisian population with T1D. METHODS: The study compared 122 children and adolescents with T1D with 97 controls. Genomic DNA was collected from 116 patients and 91 controls. Lipid parameters were determined by automated methods. PON1 activity was measured by a spectrophotometric method and genotyping of the PON1 gene was assessed by multiplex polymerase chain reaction followed by restriction fragment-length polymorphism. RESULTS: A significant increase in total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)) and a significant decrease in apolipoprotein A1 (ApoA1), ApoA1/ApoB ratio, and PON1 activity/HDL-C ratio were observed in children with T1D compared with controls. In the LLQR haplotype, the group with diabetes showed significantly higher values of total cholesterol, LDL-C, apoB, Lp(a), and apoA1/apoB ratio compared with the control group. Those with diabetes with the LLQQ haplotype showed a significant decrease in LDL-C and Lp(a) compared with controls (P < .0001). CONCLUSION: PON1 polymorphisms (PON1-55 and PON1-192) seem to be involved in the altering the lipid profile in T1D. The LLQR haplotype provided an atherogenic lipid profile in children with T1D compared with controls. LLQQ haplotype seemed to have a protective effect against the increase in LDL-C and Lp(a) that are heavily involved in the development of cardiovascular diseases.

Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes.

BACKGROUND: Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H + -ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies. METHODS: 25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing. RESULTS: In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c.1102G > A; p.Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p.Met408Cysfs*10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19. CONCLUSION: Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1B1 and four different ATP6V0A4 mutations in 25 Tunisian children. One of them, c.1102G > A; p.Glu368Lys in the ATP6V1B1 gene, had not previously been described. Among deaf since childhood patients, 75% had the ATP6V1B1 gene c.1155dupC mutation in homozygosis. Based on the results, we propose a new diagnostic strategy to facilitate the genetic testing in North Africans with dRTA and SNHL.

Steroid 21-hydroxylase gene mutational spectrum in 50 Tunisian patients: characterization of three novel polymorphisms.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease of steroid biosynthesis in humans. More than 90% of all CAH cases are caused by mutations of the 21-hydroxylase gene (CYP21A2), and approximately 75% of the defective CYP21A2 genes are generated through an intergenic recombination with the neighboring CYP21A1P pseudogene. In this study, the CYP21A2 gene was genotyped in 50 patients in Tunisia with the clinical diagnosis of 21-hydroxylase deficiency. CYP21A2 mutations were identified in 87% of the alleles. The most common point mutation in our population was the pseudogene specific variant p.Q318X (26%). Three novel single nucleotide polymorphism (SNP) loci were identified in the CYP21A2 gene which seems to be specific for the Tunisian population. The overall concordance between genotype and phenotype was 98%. With this study the molecular basis of CAH has been characterized, providing useful results for clinicians in terms of prediction of disease severity, genetic and prenatal counseling.

Molecular epidemiology and clinical characterization of group A rotavirus infections in Tunisian children with acute gastroenteritis.

Rotaviruses are the most common cause of severe viral gastroenteritis in early childhood worldwide. Thus, the objectives of our study were to determine the molecular epidemiology and the clinical features of rotavirus gastroenteritis in Tunisia. Between January 2003 and April 2007, a prospective study was conducted on 788 stool samples collected from children under 12 years of age who were suffering from acute gastroenteritis. Rotavirus was detected by multiplex RT-PCR in 27% (n = 213) of samples, among them 79.3% (n = 169) cases were monoinfections. The frequency of rotavirus infections was significantly higher among inpatients (29%) than among outpatients (13%) (P < 0.001). The seasonal distribution of rotavirus diarrhea showed a winter peak, with an unusual peak from June to September. The mean duration of hospitalization was 6.5 ± 8.1 days and the mean age was 15.8 ± 22.8 months for rotavirus monoinfections. Fever, vomiting, abdominal pain, and dehydration were observed in 88, 98, 13, and 80 cases, respectively, in children with rotavirus monoinfections. G3P[8] (45.6%) and G1P[8] (23.9%) were the most common genotypes found in our study. The determination of rotavirus infection prevalence and the characterization of the rotavirus strains circulating will help us to better understand the molecular biology and epidemiology of the disease in our country.

Molecular detection of genogroup I sapovirus in Tunisian children suffering from acute gastroenteritis.

This study investigated the prevalence of sapovirus infections in children with acute gastroenteritis in Monastir region, Tunisia, from January 2003 to April 2007. Sapovirus was characterized by sequence and phylogenetic analyses of the partial polymerase gene. From 788 fecal specimens tested, 6 (0.8%) were positive for sapovirus, of these, 4 (66.7%) were monoinfections. All sapovirus positive samples were detected in outpatient, contrary to norovirus which was significantly more frequent in hospitalized children than in outpatients (14.5 vs. 9.5%, P = 0.03). The mean age of children with sapovirus infections was 11 ± 5.56 months (range 6-19 months). Sapovirus isolates were detected in March and between September and December 2003. Fever, vomiting, abdominal pain, and dehydration were not observed in patients with sapovirus infections. Analysis of nucleotide and amino acid sequences revealed that all 6 Tunisian sapovirus strains clustered in the GGI/1 genotype and strains were identical in the region sequenced, sharing 90.2% nucleotide identity with the reference strain Sapporo/82/JP (U65427). This represents the first finding of sapovirus infections in North Africa and especially in Tunisia. The data indicate that, contrary to norovirus which can cause severe diarrhea and is an important etiologic agent in hospitalized cases, sapovirus causes mild gastroenteritis in Tunisian children.

Aichi virus IgG seroprevalence in Tunisia parallels genomic detection and clinical presentation in children with gastroenteritis.

Aichi virus has been described as a novel causative agent of gastroenteritis in humans. In this study, we report the seroprevalence distribution of Aichi virus in Tunisia. A panel of 1,000 sera was screened by applying an enzyme-linked immunosorbent assay for immunoglobulin G specific for Aichi virus. A considerable prevalence (92%) of antibody to Aichi virus was found across all age groups. The specific anti-Aichi virus antibodies increased with age, from a high rate (68.8%) in children under 10 years old to about 100% in persons more than 60 years old. We found a statistically significant increase in levels of antibody to Aichi virus according to the age of patients. Immunoglobulin M antibodies were detected among five children. A high frequency of Aichi virus monoinfections in hospitalized children with severe gastroenteritis was previously observed in Tunisia. Aichi virus causes diarrhea with dehydration, fever, and vomiting. This work is the first to establish a correlation between the high seroprevalence of specific Aichi virus antibodies, clinical presentation, and a high frequency of isolation of Aichi virus by genomic characterization in stools of children suffering from gastroenteritis. Our data show the importance and emerging character of Aichi virus in the viral etiology of pediatric gastroenteritis.

Molecular epidemiology of human astrovirus and adenovirus serotypes 40/41 strains related to acute diarrhea in Tunisian children.

Human astrovirus (AstV) and adenovirus types 40 and 41 (AdV 40/41) are responsible for epidemic and endemic acute gastroenteritis in children and adults. The present study was designed to evaluate the prevalence and genetic diversity of enteric viruses in children in Tunisia. A total of 788 fecal samples were collected during a 4-year period in the region of Monastir, from children under 12 years old, hospitalized or presenting in dispensaries with symptoms of acute gastroenteritis. AstV and AdV40/41 were detected by immunoenzymatic methods and confirmed by PCR/RT-PCR and sequence analysis. Phylogenetic analyses were performed for nucleotide homology with reference strains. AstV and AdV40/41 were characterized as a causative agent in 28 (3.6%) and 18 (2.3%) of the fecal samples, respectively. Phylogenetic analysis showed that the AstVs belonged to the serotypes 3 (n = 4; 14.3%) and 1 (n = 24; 85.7%), and the enteric AdVs to the serotypes 40 (n = 1; 5.6%) and 41 (n = 17; 94.4%). This is the first report that describes the molecular epidemiology of AstV and AdV40/41 in Tunisian children. Their respective detection rate was very low, far below that of rotavirus and norovirus. The genetic diversity among these two viruses is relatively limited and varies depending on the area.

Detection and genomic characterization of Aichi viruses in stool samples from children in Monastir, Tunisia.

Aichi virus has been associated with acute gastroenteritis in adults and children. Stool samples were collected from 788 Tunisian children suffering from diarrhea. Aichi virus was found in 4.1% of the cases. The high proportion of monoinfections and the high frequency of hospitalizations support the role of Aichi virus in pediatric gastroenteritis.