Occurrence of Hypopituitarism in Tunisian Turner Syndrome patients: familial versus sporadic cases.

OBJECTIVE: To explore unusual association between Turner Syndrome (TS) and Hypopituitarism in a Tunisian cohort. METHODS: We reported 6 patients with TS associated to Hypopituitarism, including three familial cases except the fourth sister who showed only a TS phenotype. Biochemical analysis, resonance magnetic imaging and cytogenetic analyses were performed. RESULTS: The average age of our patients was 17.2 years (11-31 years). They were all referred for short stature and pubertal delay, except for the fourth sister who presented spontaneous puberty with the integrity of the pituitary axis and the presence of an X ring chromosome. Karyotype analysis showed monosomy in 3 cases and a mosaic TS in the 3 remaining cases, including one patient with abnormal X chromosome structure. Somatotropic and corticotropic deficiencies were confirmed in 2 sporadic cases while the gonadotropic and thyrotropic axes were spared. In contrast; familial cases were consistently affected by the integrity of the corticotropic axis. MRI showed pituitary hypoplasia in all familial cases and pituitary stalk interruption syndrome in only one sporadic case. No correlation was found between the chromosome formula and the anterior pituitary involvement. CONCLUSION: Co-segregation of congenital Hypopituitarism with pituitary hypoplasia and X chromosome aberrations could imply a molecular anomaly of transcription factors responsible for the differentiation and development of pituitary cells such as PROP1, POUF1, Hesx1, Lhx3, Lhx4. The etiopathogenic link between X chromosome abnormalities and the occurrence of Hypopituitarism remains unclear; however, the progress of molecular biology may clarify the interrelation between transcription factors and sex chromosome segregation abnormalities.

Comorbidity in the Tunisian population.

Genetic diseases in the Tunisian population represent a real problem of public health as their spectrum encompasses more than 400 disorders. Their frequency and distribution in the country have been influenced by demographic, economic and social features especially consanguinity. In this article, we report on genetic disease association referred to as comorbidity and discuss factors influencing their expressivity. Seventy-five disease associations have been reported among Tunisian families. This comorbidity could be individual or familial. In 39 comorbid associations, consanguinity was noted. Twenty-one founder and 11 private mutations are the cause of 34 primary diseases and 13 of associated diseases. As the information dealing with this phenomenon is fragmented, we proposed to centralize it in this report in order to draw both clinicians' and researcher's attention on the occurrence of such disease associations in inbred populations as it makes genetic counseling and prenatal diagnosis challenging even when mutations are known.

[Primary distal renal tubular acidosis in children in the South of Tunisia: study of 15 cases]. / L'acidose tubulaire distale primitive de l' enfant : etude de 15 observations.

BACKGROUND: primary distal renal tubular acidosis in children (RTA) is characterized by metabolic acidosis due to defect in urinary excretion of hydrogen (H+) in the distal tubular. AIM: To report the epidemiological, clinical, therapeutic and evolutionary of distal RTA in our patients. PATIENTS AND METHODS: We conducted a retrospective study of all cases of distal RTA collected in the department of pediatrics of Hedi Chaker University hospital in the south of Tunisia, during a period of 23 years (1988-2010). We studied the epidemiological, clinical, biological, evolutionary and therapeutic data. RESULTS: During the study period 15 cases of distal RTA were collected. The average age was 6 months (1 month -2 years). Most common presenting symptoms were vomiting (8cases), failure to thrive (4cases), lack of appetite, polyuria-polydipsia syndrome (1case) and urinary infection (2cases). The clinical examination showed staturoponderal delay (9 cases), dehydration (6 cases), signs of rickets (3 cases) and polyuria (10 cases). Biological data showed high urine pH in the presence of metabolic acidosis in 11 cases, hypokalaemia in 10 cases and hypercalciuria in all cases. Urine acidification test with ammonium chloride was performed in 4 cases, the urinary pH was always higher than 5.5 in all cases. Ammoniuria performed in 9 cases was less than 40mmol/l. Radiological investigation objectified a nephrocalcinosis in fourteen patients and signs of rickets in three cases. Deafness was found in three patients. Genetic study performed in two cases showed mutation of ATP6V1B1 gene. The medical treatment involved an alkali load. Long-term outcome was favorable in 7 cases. CONCLUSION: The distal renal tubular acidosis is a rare pathology in our country but probably under diagnosed. The clinical gravity of this disease and the risk of evolution towards the terminal renal insufficiency justify an antenatal diagnosis to establish a neonatal management or propose a therapeutic interruption of the pregnancy if the distal RTA is associated with a severe pathology.

[Pediatric Crohn's disease in Tunisia]. / La maladie de Crohn de l'enfant en Tunisie.

UNLABELLED: Crohn's disease occur mainly in adults. However, pediatric onset forms are not rare and have many characteristics. AIM: to study clinical, diagnostic, therapeutic and evolutive characteristics of crohn's disease in tunisian children. METHODS: Retrospective multicenter study conducted in 10 pediatric departments on a period of 10 years (2000-2008) RESULTS : 43 children were included. The sex-ratio was 1.68. The mean age at the onset of the symptoms was 11+/-2.3 years (5-16 years). The age of onset was inferior to 10 years in 25 % of the children. The delay before management was superior to 1 year in 25% of cases. The initial symptoms were dominated by diarrhea (95%). Perineal manifestations were present at diagnosis in 30% of children and extra-digestive manifestations in 53%. Ileocolonic localization was the most frequent (46%). The initial disease flare was moderate in 83% of cases. The treatment was medical in 77 % of cases, nutritional and medical in 18.5%. Maintenance therapy was instituted in 86% of cases and consisted essentially in azathioprin (62%). The mean follow-up was 3 years and 4 months. 60% of the children had at least one acute flare. During evolution, 7% of children had anoperineal surgery and 11% an intestinal resection. CONCLUSION: Crohn's disease seems rare in Tunisia. The time of diagnosis is often delayed. The management is based on immunosuppressive therapy and nutritional support.

[Epidemiology of rotavirus gastroenteritis among children under 5 years of age in Tunisia - results of sentinel hospital surveillance 2009 to 2011]. / Épidémiologie des gastroentérites à rotavirus chez les enfants âgés de moins de cinq ans en Tunisie - Résultats de la surveillance sentinelle hospitalière 2009 à 2011.

BACKGROUND: Rotavirus is the major cause of severe acute gastroenteritis among young children. The objectives of this study were to assess the epidemiology, clinical and virological features of community-acquired rotavirus acute gastroenteritis, in children under 5 years of age, hospitalized in Tunisia. METHODS: A multicenter prospective observational study was conducted from April 2009 to March 2011, in 11 sentinel pediatric departments. Clinical data and stool samples were collected for all children under 5 years, admitted for acute gastroenteritis. Rotavirus was detected by Elisa immunoassay test and genotyped for G and P by semi-nested multiplex RT-PCR. RESULT: A total of 621 children were enrolled in this study. Rotavirus was detected in 30.3% of cases (95% CI [26.7-33.9]). The estimated incidence rate of rotavirus acute gastroenteritis was 11 cases/100,000 child-years (95% CI [9.43-12.57]). This infection affected predominantly children aged under 24 months, and occurred mainly in winter (55.3%). Vomiting, fever and dehydration were observed in 79.6%, 69.5% and 57% respectively. Genotype analysis identified four G types (G1, G2, G3 and G4) and 4 P types (P[4], P[6], P[8] and P[9]). The most common G/P combination was G3P[8] (24.4%), followed by G4P[8] (13.3%) and G1P[8] (6.5%). CONCLUSION: These results highlight the frequency and potential severity of rotavirus acute gastroenteritis in pediatric hospital settings. The present study could provide a sufficient database to make a decision related to the introduction of rotavirus vaccine in Tunisian national immunization program.

Relationship between electropherotypes and VP7/VP4 genotypes of group A rotaviruses detected between 2000 and 2007 in Tunisian children.

BACKGROUND: Rotaviruses are the most frequent agents associated with diarrhoea in children worldwide. Analysis of mobility of the 11 segments of genomic RNA by polyacrylamide gel electrophoresis (PAGE) yields a pattern which is characteristic for a particular rotavirus isolate. The group A rotaviruses can be further characterized by analysis of VP7 and VP4 genes specificities, responsible for rotavirus classification into G and P genotypes, respectively. The aim of the present study was to detect a relationship between electropherotype pattern and molecular characteristics of the rotavirus strains. MATERIAL AND METHODS: Were analyzed 278 rotavirus-positive specimens by PAGE and G/P-genotyped by multiplex semi-nested RT-PCR. Pearson's correlation tests were used for statistical analysis. RESULTS: Twelve different electropherotypes were visualized, eight with a long profile (186 cases) and four with a short one (87 cases). Concerning VP7 types, G2 viral strains were found to be predominant and were detected in 91 specimens (32.7%). Strains with G1, G3, G4, G8 and G9 specificities were detected in 62 (22.3%), 82 (29.5%), 13 (4.7%), two (0.7%) and seven cases (2.5%), respectively. The results of VP4 genotyping showed a predominance of P[8] genotype which comprised half of the strains identified (139 cases, 50%). VP4 P[4], P[6] and P[11] were found in 83 (29.9%), 31 (11.1%) and 11 (4.0%) specimens, respectively. A high rate of mixed strains was also found (1.8% mixed electropherotypes, 7.6% G-mixed and 5% P-mixed strains). Electropherotype pattern of rotavirus strains was significantly correlated with VP7 genotype (p=0.018) and with VP4 genotype specificities (p<0.001).

[Evolution of group A Rotavirus strains circulating in Tunisia over a 3-year period (2005-2007)]. / Évolution des souches de Rotavirus du groupe A en circulation en Tunisie sur une période de trois ans (2005-2007).

BACKGROUND: Rotaviruses are the most frequent agents associated with diarrhoea in children worldwide. Analysis of mobility of the 11 segments of genomic RNA by polyacrylamide gel electrophoresis (PAGE) yields a pattern which is characteristic for a particular rotavirus isolate. The group A rotaviruses can be further characterized by analysis of VP7 and VP4 genes specificities, responsible for rotavirus classification into G and P genotypes, respectively. The aim of the present study was to determine the evolution of group A Rotavirus strains circulating in Tunisia over a 3-year period (2005-2007). MATERIAL AND METHODS: A total of 1503 stool samples collected from children less than five years old, consulting or hospitalised in Tunisia for diarrhoea between 2005 and 2007, were screened for the presence of group A Rotaviruses. Rotavirus-positive specimens were further analyzed by PAGE and G/P-genotyped by multiplex semi-nested RT-PCR. RESULTS: Rotaviruses were detected in 323 stool samples over 1503 (21 %). Long electropherotypes predominated in Tunisia during the whole period of study (N=158 vs N=82 short electropherotypes). VP7 genotyping showed the cocirculation of five different genotypes: G1, G2, G3, G4 and G9. VP4 typing detected four different P-genotypes: P[8], P[4], P[6] and P[11]. Rotavirus strains with G3P[8] specificity were predominating in Tunisia in 2005 and 2006, replaced by G2P[4] strains in 2007.

Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis.

Human neutrophils at inflammatory sites may be an important source of the chemotactic cytokines macrophage inflammatory protein 1 alpha (M1P-1 alpha; a C-C chemokine) and interleukin 8 (IL-8; a C-X-C chemokine). In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils. Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha. Since inflammatory cytokines are likely to be present in the synovium during crystal-induced inflammation, we examined the interaction between TNF-alpha and GM-CSF and the crystals. Both TNF-alpha and GM-CSF stimulated IL-8 production; however, only TNF-alpha exerted a significant effect on MIP-1 alpha secretion in neutrophils. IL-8 production induced by TNF-alpha and GM-CSF was synergistically enhanced in the presence of MSU or CPPD, whereas MIP-1 alpha secretion induced by TNF was completely inhibited in the presence of either MSU or CPPD. Interestingly, no interaction between the crystals and the inflammatory cytokines was observed with respect to synthesis of the C-X-C chemokine MGSA in neutrophils. These results suggest that the combination of TNF-alpha and GM-CSF with MSU or CPPD will lead to the production of IL-8 by neutrophils and abolish the release of MIP-1 alpha, an event that will theoretically lead to recruitment of neutrophils but not mononuclear cells. These results are in accordance with the pathological state of gout and pseudogout, where the predominant inflammatory cell is the neutrophil.

Lipoxin (LX)A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor 1alpha-initiated neutrophil responses and trafficking: regulators of a cytokine-chemokine axis.

The impact of lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-alpha-initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1-10 nM, the LXA4 and ATL analogues each inhibited TNF-alpha-stimulated superoxide anion generation and IL-1beta release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-alpha, as these responses were not altered with either GM-CSF- or zymosan-stimulated cells. TNF-alpha-induced IL-1beta gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-alpha-stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1beta, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-alpha-directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.

[A childhood case of antiphospholipid syndrome]. / Le syndrome des antiphospholipides à propos d'une nouvelle observation pédiatrique.

UNLABELLED: Many conditions can lead to cerebral strokes in children. The antiphospholipid syndrome widely described in adults in association with systemic lupus erythematosus, is rare in childhood. CASE REPORT: Two months after recovering from varicella and a few days after an episode of bronchitis, a 17-month-old girl developed left facial paralysis associated with right hemiplegia. Brain MRI and angio-scan showed thrombosis in the internal left carotid associated with ischemia in the superficial posterior territory of the left Sylvian artery. Echocardiography and hemoglobin electrophoresis were normal. Tests were negative for protein S, C and antithrombin III deficiencies and no resistance to activated protein C. IgM anticardiolipin antibodies were detected at high level (greater than 25IU/l) initially and six weeks later. In the absence of an evident etiology, mainly systemic lupus erythematosus (negative antinuclear antibodies), the diagnosis of primary antiphospholipid syndrome was retained. The girl was treated by heparin then by salicylate at antiaggregate doses associated with re-habilitation. Twelve months later, the patient had not developed any other thrombosis, in spite of a high level of anticardiolipin antibodies. CONCLUSION: In children with cerebral strokes, antiphospholipid syndrome must be discussed when the usual etiologies have been ruled out.

[Primary rhabdomyosarcoma of the pleura presenting as recurrent pneumothorax]. / Pneumothorax récidivant révélateur d'un rhabdomyosarcome primitif de la plèvre.

INTRODUCTION: Rhabdomyosarcoma is the most common soft tissue sarcoma in the first two decades of life. Its most common location is the head and neck. It rarely arises in the thorax including the pleura. There are only 7 previously reported cases in the literature. We report a case of primary pleural rhabdomyosarcoma with an unusual clinical presentation and location. Our aim is to discuss the clinical presentation, treatment and prognosis of this uncommon location of rhabdomyosarcoma. CASE REPORT: We report a case of primary embryonal rhabdomyosarcoma of the pleura in a boy of 21 months. The presentation was characterized by recurrent spontaneous pneumothorax. A computed tomography scan showed only pleural detachment with no evidence of any pleural disease. The malignant cells incidentally found in routine pleural biopsy were the diagnostic clue. The rhabdomyoblastic nature of these cells was confirmed by positive immunostains for myoD1 and desmin. Investigation for metastases was negative. Despite chemotherapy, the tumour quickly increased in size and the infant died from acute respiratory failure. CONCLUSION: Thoracic rhabdomyosarcoma is rare and remains clinically silent for a long time. Its management is still controversial. Prognosis is generally poor when compared with other locations.

[Aplasia cutis congenita of the scalp (5 observations)]. / Aplasia cutis congenita du vertex (5 observations).

UNLABELLED: Aplasia cutis congenita (ACC) is an uncommon congenital malformation. It is characterized by defects of the skin that occur most frequently on the scalp along the midline, but can also be localized on the trunk, face and limbs, usually with a symmetrical distribution. When it is localized in the skull, it can extend to the dura mater, with only the thin pia mater to protect the brain. PATIENTS AND METHODS: We report a retrospective study during a period of 10 years and we report 5 cases of ACCV hospitalized in the pediatric service in CHU Hédi Chaker and in maxillo-facial surgery service in CHU Habib Bourguiba, Sfax. We studied the epidemiologic, clinical, and therapeutic aspects in our patients. RESULTS: The average age at the admission was 5 days (2-8 days). A consanguinity was found in 2 cases. The clinical examination revealed cutaneous and osseous structures aplasia located in frontoparietal zone in 3 patients and in parieto-occipital zone in a patient. A hypoplasia of the toes was noted in 3 cases and a hypoplasia of the 3rd finger of the 2 hands in a case. Plain X-ray skull (3 cases) showed the osseous defect in all the cases. The cerebral IRM (2 cases) showed osseous and cutaneous defect in two cases and a lipome of the corpus callosum in one patient. A surgical repair using a cutaneous graft was performed for 3 patients. A patient died on the 16th day of life from a haemorrhage of the longitudinal sinus. The evolution was favourable in 4 cases with a cicatrisation of good quality but with subsequent alopecia. CONCLUSION: ACC of the scalp is a rare and often sporadic affection. Our experience confirms that fatal bleeding from the longitudinal sinus can occur during the 1st weeks of life.

[Moyamoya and Down syndrome: about 2 cases]. / Syndrome de Moyamoya et trisomie 21 : à propos de 2 cas.

Moyamoya syndrome has rarely been reported in association with Down syndrome. We report on 2 cases in 3-year-old and 6-year-old female children with Down syndrome, who presented with neurological deficit. Imaging (magnetic-resonance angiography and digital-subtraction angiography) revealed the classical Moyamoya pattern. The neurological deficits persisted in both cases. One patient has developed epilepsy.

Fulminant mulch pneumonitis in a previously healthy child.

Chronic granulomatous disease (CGD) is associated with multiple and recurrent infections. In patients with CGD, invasive pulmonary infection with aspergillus species remains the greatest cause of mortality. Acute fulminant presentations of fungal pneumonia are catastrophic. It is a medical emergency, and currently the treatment is based on association of corticosteroids and antifungal therapy. We describe the case of an 11-year-old boy, with late initial presentation of CGD, which was revealed by fulminant aspergillus pneumonia. He was successfully treated with an association of high doses of steroids and voriconazole.

[Management of patients with major beta thalassemia in a paediatric department in the south of Tunisia: About 26 cases]. / Prise en charge thérapeutique des patients atteints de bêta-thalassémie majeure dans un service de pédiatrie du sud tunisien : à propos de 26 cas.

AIM: Our objectives were to assess the management of patients with major thalassemia and identify the various complications and monitoring means. PATIENTS AND METHODS: A retrospective study was conducted on 26 ß-thalassemic patients in the department of paediatrics, Hédi Chaker hospital, Sfax, Tunisia during a period of 25 years (from 1 January 1990 to 31 December 2014). RESULTS: The mean age of the beginning of transfusion was 11.5 months. That was with phenotyped red blood cells but not leukodepleted blood. Twenty-three patients received chelation. Before 2001, all patients received deferoxamine, poor adherence to this treatment was observed in 66% of cases. It was replaced by deferiprone since 2006 and deferasirox since 2009. A combination of 2 or 3 chelators was indicated for four patients. A total splenectomy was performed in 10 cases patients; it was due to hypersplenism. The bone marrow transplant was performed for one patient at the age of 9 year but it was rejected. Many complications were detected: endocrine complications (19 cases), immune complications (9 cases), gallbladder stones (5 cases), cardiac complications (4 cases), osteoporosis (3 cases), infectious complications (3 cases) and thromboembolic complications (2 cases). We noted some side effects related to chelation therapy in twelve cases. Four patients were dead. CONCLUSION: Improving the medical care of homozygous ß-thalassemic children requires adherence to transfusion regimen and chelation therapy. Bone marrow transplantation remains the only possible curative therapy, which must be promoted in our country.

[Virus and Atypical Pathogens Detected in Community-Acquired Lower Respiratory Tract Infection in Infants and Children of Sfax Region, Tunisia]. / Virus et bactéries atypiques détectés dans les infections respiratoires basses communautaires de l'enfant dans la région de Sfax en Tunisie.

Little is known about viral and atypical bacteria pathogen spectra of community-acquired lower respiratory tract infection in children in Tunisia. Thus, a prospective study was carried out between January 2009 and March 2010 in Sfax. Nasopharyngeal aspirates collected from 368 patients (78 with pneumonia and 290 with acute bronchiolitis) were analyzed by indirect immunofluorescence assay and PCR to detect influenza viruses, parainfluenza viruses, respiratory syncytial virus (RSV), human metapneumovirus, human rhinovirus, human enterovirus, adenovirus, coronavirus, Mycoplasma pneumonia (Mpn) and Chlamydia pneumonia (Cpn). One or more etiology was documented in 319 cases (86.7%). The most detected viruses were RSV (42.7%), rhinovirus (32.9%) and adenovirus (28.5%). Co-detection of two or three pathogens was found in 40% of positive samples. This study highlights the importance of respiratory viruses in lower respiratory tract infection in children of Sfax region as well as the high rate of co-detection of multiple viruses, resulting in challenges in clinical interpretation.

Le profil étiologique microbien des infections respiratoires basses (IRB) communautaires de l'enfant a été peu étudié en Tunisie. Une étude prospective a été menée à Sfax entre janvier 2009 et mars 2010 sur 368 enfants hospitalisés pour pneumonie (n = 78) ou bronchiolite aiguë (n = 290). Les aspirations nasopharyngées ont été analysées par immunofluorescence et par PCR à la recherche des virus influenza, virus para-influenza, virus respiratoire syncytial (VRS), métapneumovirus, rhinovirus, entérovirus, adénovirus, coronavirus, Mycoplasma pneumoniae (Mpn) et Chlamydia pneumoniae (Cpn). Une étiologie ou plus a été retrouvée dans 319 cas (86,7 %) : principalement le VRS (42,7 %), des rhinovirus (32,9 %) et des adénovirus (28,5 %). Dans 40 % des prélèvements positifs, deux ou trois agents pathogènes ont été codétectés. Cette étude a permis de montrer la prévalence élevée des virus dans les IRB de l'enfant dans la région de Sfax et leur détection fréquente en co-infection posant la question sur leur rôle pathogène réel.

[Susceptibility markers in Tunisian first-degree relatives of patients with type 1 diabetes]. / Marqueurs de risque du diabète de type 1 chez les apparentés au premier degré des diabétiques tunisiens.

To identify the profile of anti-pancreas autoantibodies and elucidate the HLA DRB1, DQB1 polymorphism in Tunisian first-degree relatives of patients with type 1 diabetes, we recruited 96 relatives from 21 families with at least one diabetic child. Islet cell antibodies (ICA) were detected by immunofluorescence on monkey pancreas; glutamate decarboxylase (GADA), IA2 (IA2-A) and insulin (IAA) antibodies were measured by RIA. HLA class II DRB1 and DQB1 alleles were typed by PCR-SSP. ICA, GADA, IA2-A and IAA were found in respectively 11.5, 4.2, 5.2 and 8.3% of relatives. Twenty-two out of 96 had at least one antibody and 20 out of these 22 had a susceptibility allele (DRB1*03, DRB1*04, DQB1*02 or DQB1*0302) with or without protective allele (DRB1*11, DRB1*13, DRB1*15 or DQB1*06). All of the 5 relatives having 2 autoantibodies or more carried the DRB1*04-DQB1*0302 susceptible haplotype. In conclusion, this observational study confirms in a Tunisian population known epidemiological data and demonstrates the usefulness of follow-up to determine the predictive value of studied markers.

Transient neonatal diabetes mellitus and activating mutation in the KCNJ11 gene in two siblings.

Transient neonatal diabetes mellitus is a rare disease usually associated with chromosome 6 abnormalities. Mutations of the genes encoding the potassium channel are rarely associated with these transitional forms. Herein, we report the clinical features of two siblings with a heterozygous mutation C679 G>A in the KCNJ11 gene.

Familial haemophagocytosis lymphohisticytosis type 3: A case report.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder of immune regulation. Here, we report on a fatal case of type 3 FHL (FHL3) in a 45-day-old boy. Clinically, the infant presented with fever and hepatosplenomegaly. Biology showed pancytopenia, elevated ferritin, and decreased fibrinogen. Images of hemophagocytosis were found at the bone morrow examination. The diagnosis of FHL type 3 was made by the identification of homozygous mutation in the Munc13-4 gene (UNC13D) located in exon 20: 1822 del 12bp (V608fs). This mutation was previously observed in a Tunisian and in Moroccan families.

CREM variant rs17583959 conferred susceptibility to T1D risk in the Tunisian families.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic ß-cells by autoreactive T cells. Studies in animal models, such as the non-obese diabetic (NOD) mouse reveal that this disease is under the control of several genes that encode molecules implicated in regulation of transcription factors and in T cell activation. In order to underline the role of the genes involved in this regulation pathways, we investigated, using the Sequenom MassARRAY platform, 13 single-nucleotide polymorphisms (SNPs) belonging to CREM, IRF5, STAT4, and STAT5a/b genes in 59 T1D Tunisian families. In the current study, we identified an association with rs17583959 (allele G; Z score=2.27; p=0.02; Genotype GG: score=1.96; p=0.04) of CREM gene. In LD analysis a strong LD between the 3 CREM variants (Block 1) was detected; rs2384352 was in complete LD with rs1148247. When haplotypes were constructed between CREM polymorphisms (rs1148247, rs17583959, rs2384352), AGA haplotype (H2) was significantly over-transmitted from parents to affected offspring (Z score=2.988; P=0.002) and may confer a risk for T1D disease. Whereas, AAG haplotype (H5) (Z score=-2.000; p=0.045) was less transmitted than expected to affected children suggesting its protective effect against T1D pathology. No significant association in IRF5, STAT4, and STAT5a/b genes were observed. In conclusion, this study shows an eventually involvement of CREM gene in the development of T1D pathology in Tunisian families. These facts are consistent with a major role for transcription factor genes involved in the immune pathways in the control of autoimmunity. Further researches of association and functional analysis across populations are needed to confirm these findings.