Management of a giant retroperitoneal leiomyoma: a case report.

BACKGROUND: Leiomyomas are benign tumors observed mainly in adult women. The retroperitoneum is a rare location for leiomyomas; almost 100 cases have been reported. Because retroperitoneal leiomyomas are paucisymptomatic and the tumor size at diagnosis is relatively large, surgical management is challenging. Regular follow-up is required because recurrence and malignant sarcomatous transformation have been described in a few cases. CASE PRESENTATION: We report a case of a 52-year-old North African woman with a 22-cm retroperitoneal leiomyoma. A preoperative embolization was performed 2 days before surgery. The clinical, therapeutic, and evolutive aspects of this rare entity are discussed. CONCLUSIONS: Despite its benignity, retroperitoneal leiomyoma is a challenging diagnostic, therapeutic, and evolutive condition. Surgeons must consider mainly the tumor's vascularization. Regular follow-up is mandatory because malignant transformation cannot be excluded.

[Neonatal expression of beta-thalassemia trait associated with hereditary spherocytosis in two monozygotic twins]. / Expression néonatale d'un trait bêta-thalassémique associé à une sphérocytose héréditaire chez deux jumelles monozygotes.

The beta-thalassemia trait is a heterozygous beta-thalassemia characterized by a partial deficiency of the synthesis of beta-globin chains of hemoglobin. It is usually asymptomatic and the diagnosis is often made on the occasion of the completion of a systematic blood count or a family survey. Clinical expression during the neonatal period is impossible and its association with hereditary spherocytosis is common. We report two monozygotic twins who, on the 3rd day of life, presented intense jaundice, unconjugated bilirubin associated with anemia, without hepatosplenomegaly. Laboratory tests found nonimmune hemolytic anemia with microcytosis and hypochromia justifying iterative blood transfusions. The etiological investigation found heterozygous beta-thalassemia associated with hereditary spherocytosis. The family investigation and molecular analysis objectified the beta-thalassemic mutation IVS1nt110 (G→A) in the heterozygous state in the twins, the father, the mother, and in one of the two brothers. With any nonimmune hemolytic anemia in newborns, the etiological investigation should be systematic for early diagnosis and to plan appropriate treatment.

Mutations and polymorphisms in N-acetylgalactosamine-6-sulfate sulfatase gene in Turkish Morquio A patients.

Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive inherited metabolic disease resulting from deficiency of N-acetylgalactosamine-6-sulfatase (GALNS). This lysosomal storage disorder leads to a wide range of clinical variability ranging from severe, through intermediate to mild forms. The classical phenotype of Morquio A disease is characterized by severe bone dysplasia without intellectual impairment. Two severe MPS IVA patients from two unrelated Turkish families have been investigated. The 14 exons and intron-exon junctions of the GALNS gene were sequenced after amplification from genomic DNA. Direct sequencing revealed two homozygous mutations previously described: p.L390X in exon 11 and p.W141R in exon 4. The p L390X mutation was associated with four novel polymorphisms in intron 2, intron 5 and intron 6 and one polymorphism previously described in exon 7. We have analysed the haplotypes associated with the two identified mutations. These molecular findings will permit accurate carrier detection, prenatal diagnosis and counseling for Morquio A syndrome in Turkey.

High intensity exercise affects diurnal variation of some biological markers in trained subjects.

The study investigated if markers of muscle injury and antioxidant status were affected by a Wingate test performed at 2 different times of day. 15 young male footballers performed 2 tests (randomized) at 07:00-h and 17:00-h. Fasting blood samples were collected before and 3 min after each test for assessment of markers of muscle injury and antioxidant status. Resting oral temperature was recorded during each session. Peak power (10.76 ± 1.05 vs. 11.15 ± 0.83 W.kg( - 1)) and fatigue index (0.41 ± 0.04 vs. 0.49 ± 0.13%) during the Wingate test, and core temperature, were significantly higher (all p<0.05) in the evening. Markers of muscle injury were significantly higher in the evening before and after exercise (e. g., 148.7 ± 67.05 vs. 195 ± 74.6 and 191.6 ± 79.52 vs. 263.6 ± 96.06 IU.L (- 1), respectively, for creatine kinase; both p<0.001). Antioxidant parameters increased after the Wingate test but only resting values were significantly higher in the morning (e. g., 1.33 ± 0.19 vs. 1.19 ± 0.14 µmol.L (- 1) for total antioxidant status; p<0.05). The results indicate that muscle injury and antioxidant activity after the Wingate test were higher in the evening, suggesting a possible link between the biochemical measures and the diurnal fluctuation of anaerobic performance. However, repetition of this study after prescribed rather than self-selected exercise intensity is recommended.

Mucopolysaccharidosis IVA within Tunisian patients: Confirmation of the two novel GALNS gene mutations.

UNLABELLED: Mucopolysaccharidosis type IVA or Morquio A disease is an autosomal recessive disease resulting from a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate-sulfatase, which hydrolyses N-acetylgalactosamine-6-sulfate and galactose-6-sulfate in glycosaminoglycans. Phenotypes in Morquio A disease vary from the classical form with severe bone dysplasia, heart valve involvement, corneal opacity, short trunk dwarfism and a life span of 20 to 30 years, to attenuated forms with normal life span, mild bone involvement and mild visceral organ involvement. Unlike the other forms of mucopolysaccharidoses, Morquio A disease is characterized by normal intelligence. AIM OF THE STUDY: The aims of this study were to determine if the novel GALNS anomalies IVS1+1G-A and G66R identified in Tunisia are mutations or polymorphisms. PATIENTS AND METHODS: This study was carried out on six Morquio A patients recruited from many regions of Tunisia. We have used SCCP, sequencing and enzymatic digestion. RESULTS: IVS1+1G-A and G66R were two deleterious mutations and not polymorphisms. CONCLUSION: Screening of mutations and polymorphisms in GALNS gene provide useful information on genotype/phenotype correlations. It should also facilitate more accurate genetic counselling of newly diagnosed cases and their family members.

Molecular characterization of MPS IIIA, MPS IIIB and MPS IIIC in Tunisian patients.

Sanfilippo syndrome (mucopolysaccharidosis type III, MPS III) is a progressive disorder in which patients are characterized by severe central nervous system degeneration together with mild somatic disease. MPS III results from a deficiency in one of the four enzymes involved in the heparan sulfate degradation, with sulfamidase (SGSH), α-N-acetylglucosaminidase (NAGLU), acetyl-coenzyme A: α-glucosaminide N-acetyltransferase (HGSNAT), and N-acetylglucosamine-6-sulfatase (GNS) being deficient respectively in MPS IIIA, MPS IIIB, MPS IIIC and MPS IIID. Mutation screening using PCR reaction/sequencing analysis on genomic DNA fragments was performed in seven Tunisian index cases with MPS IIIA, three with MPS IIIB and two with MPS IIIC. QMPSF (Quantitative Multiplex PCR of Short fluorescent Fragments) analysis was developed for the detection of genomic deletions and duplications in the SGSH gene. These approaches allowed the identification of 11 mutations, 8 of them were novel including a mutation involving the start codon (p.Met1?), one small duplication (p.Leu11AlafsX22), one small deletion (p.Val361SerfsX52) and a large deletion of exon 1 to exon 5 in the SGSH gene, one missense mutation (p.Pro604Leu) and one nonsense mutation (p.Tyr558X) in the NAGLU gene and, finally, one missense mutation (p.Trp627Cys) and one nonsense mutation (p.Trp403X) in the HGSNAT gene.

[Study of the intronic polymorphism of the angiotensin 1 converting enzyme among coronary Tunisians]. / Étude du polymorphisme intronique de l'enzyme de conversion de l'angiotensine I chez des coronariens tunisiens.

BACKGROUND: The acute coronary syndromes (ACS) are classified among the major causes of mortality in the industrialized countries. The increased angiotensin I converting enzyme (ACEI) activity related to a genetic polymorphism constitutes a hereditary predisposition to these syndromes. AIM: Evaluate the ACEI activity in Tunisian patients with coronary heart disease, and investigate the association between this activity and an intronic deletion of 287 pb on the intron 16 of the ACEI gene. PATIENTS AND METHODS: Seventy-two coronary patients and 34 control subjects are recruited for our study. ACEI activity was measured by kinetic method. The intronic deletion was identified by PCR technique. RESULTS: An increased activity of ACEI was observed in patients compared with control subjects (84.38 ± 33.83 UI/L vs 59.06 ± 18.2 UI/L, P=10(-5)). The molecular study showed a raised relative frequency of D/D genotype (51.4%) among patients, whereas among the witnesses, I/I genotype prevailed (62%). D/D genotype is always associated with highest ACEI activity for the patients and the control subjects. CONCLUSION: The molecular studies and the biochemical investigations of the various parameters of cardiovascular risk (including the ACEI) direct towards a better treatment.

[Tumor Marker CA125: biochemical and molecular properties]. / L'antigène carbohydrate CA125: propriétés biochimiques et moléculaires.

Antigen carbohydrate CA125 is a tumor marker used in the monitoring of epithelial ovarian cancers. It is a transmembranaire glycoprotein with a high molecular weight. It is a mucin with a carbohydrate content estimated to be 24-28%. CA125 is encoded by the gene MUC16 which is rich of tandem repeats. Different hypothesis were suggested concerning the mechanism of secretion of CA125 that could be soluble or attached to the cellular surface. This last form of CA125 has many molecular interactions such as with mesothelin and galectin. These interactions play a key role in the stimulation and the dissemination of ovarian cancer via the tumor marker CA125.

Mucopolysaccharidoses type I and IVA: clinical features and consanguinity in Tunisia.

UNLABELLED: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by the deficiency of specific enzymes which leads to the lysosomal accumulation of glycosaminoglycanes. Mucopolysaccharidosis type I or Hurler disease is characterized by the deficiency of alpha-l-iduronidase enzyme. Mucopolysaccharidosis type IVA or Morquio A disease is due to the lack of N-acetylgalactosamine-6-sulfate-sulfatase. Theses deficiencies result in a progressive accumulation of the substrates: dermatan and heparan sulfates for Mucopolysaccharidosis type I and keratan sulfate for MPS type IVA. This process leads to progressive and chronic course for visceral attacks of the affected organs such as lungs and heart. In the Hurler disease, the nervous system is particularly affected while in Morquio a disease, a skeletal dysplasia and a normal intelligence are characteristic. AIM OF THE STUDY: This study was carried out on MPS type I and MPS type IVA unrelated families recruited from many regions of Tunisia in order to determine the relation between consanguinity and these types of disorders. PATIENTS AND METHODS: Clinical and molecular analyses confirmed the diagnosis for four MPS type I and five MPS type IVA studied families. RESULTS: First cousins unions characterize all families except one Hurler family and one Morquio A family where the consanguinity is third cousin degree. CONCLUSION: MPS type I and type IVA seems to be associated with consanguinity in Tunisia.

[Platelet-leukocyte aggregates as a marker for platelet activation in platelet concentrates]. / Complexes leucoplaquettaires en tant que marqueur d'activation dans les concentrés plaquettaires standards.

OBJECTIVES: Several in vitro laboratory tests to assess the quality control of platelet concentrates (PC) are available. Some of them have a good correlation with the platelet recovery index. To assess the quality control of standard PC prepared in our blood bank, we measured the blood gas and the degree of platelet activation. MATERIALS AND METHODS: SPC were prepared by the PRP method. Fifty-five SPC (45 SPC at day one of storage and 20 SPC at day five of storage) were analysed. Blood gas (pH, PO(2), PCO(2) and bicarbonate concentration) in the SPC were measured by blood gas automate. Platelet activation profile were determined by measuring the percentage of platelet expressing the CD62p (% CD62) and the percentage of platelet-leukocyte aggregate (% PLA). RESULTS: The pH values of all studied SPC were comprised between 7.0 and 7.6. SPC at day 1 of storage have a significantly higher pH than those at day 5 of storage (7.5+/-0.05 versus 7.3+/-0.14; p<0.001). The % CD62p were higher in SPC at day five compared to the SCP at day one without reaching a statistical significance (28.4+/-15% versus 24.3+/-9.7%, p=0.052). The percentage of PLA were higher in SPC at day one compared to SCP at day five although this difference is not statistically significant (22.2+/-7.5% versus 17.9+/-8.0%; p=0.23). CONCLUSION: Preparation and storage procedure adopted in our centre did not significantly affect the quality SPC. Our study is the first to assess the PLA in PC. Studies assessing the PLA are warranted to appreciate the clinical impact of this parameter.

[Oxidant stress and cardiovascular absolute risk in Tunisian type 2 diabetes]. / Stress oxydant et risque cardiovasculaire absolu chez des diabétiques de type 2 du centre tunisien.

INTRODUCTION: cardiovascular diseases constitute the most hefty complications in diabetes. Absolute cardiovascular risk (ACVR) can be estimated by many equations that are continuously criticised. The aim is, in one hand, to evaluate ACVR in type 2 diabetes and, in the other hand, is to establish correlations between ACVR and oxidant-antioxidant status. MATERIAL AND METHODS: 183 type 2 diabetes and 200 controls were admitted. ACVR assessment was calculated following Laurier equation. Oxidant status was evaluated by the measure of homocysteine, hydrogen peroxide (H2O2) and LDL thiobarbituric reactive oxygen substances (LDL-TBARS). Antioxidant status was evaluated by the measure of superoxide dismutase (SOD) activity, glutathione peroxidase (GPx), total antioxidant status (TAS) vitamins A, E and zinc. Glycated haemoglobin (HbA1c) and microalbuminuria were assessed by turbidimetry. RESULTS: ninety percent of diabetes belonged to moderate and high ACVR groups. In diabetic men ACVR was doubled each elevation of 4 micromol/L homocysteine, of 50 micromol/L of H2O2 and of 20 mg/L of microalbuminuria. High risk ACVR group showed the lowest SOD activity, zincemia and the highest HbA1c. No significant difference was found in LDL-TBARS, TAS, GPx, vitamins A, E between the different ACVR groups. The strong relation between homocysteine and ACVR confirms homocysteine atherosclerotic role. Homocysteine auto-oxidation produces H2O2 leading to LDL-TBARS increase. Microalbuminuria-ACVR association verifies its vasculopathy predictor role. Urinary albumin leakage may be consequent to the hyperhomocysteinemia found in diabetes. CONCLUSION: homocysteine introduction in ACVR assessment equation may ameliorate this estimation.

[Molecular analysis of the p.Asn 370 Ser mutation in Gaucher disease]. / Analyse moléculaire de la mutation p.Asn 370 Ser dans la maladie de Gaucher.

Gaucher disease is one of the most prevalent lysosomal disorders. In this present study, we report a diagnostic strategy of type 1 Gaucher disease. The application of combined methods in molecular biology allowed us to analyse the p.Asn 370 Ser mutation. The affected individual activity is very low. First, we have to used the enzymatic digestion method. Then, we have to identified the mutation by the refractory mutation system technique using specific primers for the p.Asn 370 Ser mutation. These analyses are supplemented by the direct sequencing in order to seek and confirm this mutation. Finally, the absence of the 55 pb deletion in exon 9 among corroborated the presence of the homozygous genotype of this p.Asn 370 Ser in the patient DNA.

[Biochemical and molecular diagnosis of Gaucher disease in Tunisia]. / Diagnostic biochimique et moléculaire de la maladie de Gaucher en Tunisie.

Our study was carried out at a family from the Sahel (Tunisia). The father (index case) and his two children (son and daughter). The father beta-glucocerebrosidase (GCB) activity showing a deficit. These biochemical analyses are supplemented by molecular studies: enzymatic digestion and the direct sequencing. Two mutations were analysed, the p.Asn 370 Ser and the p.Leu 444 Pro. The DNA sequencing confirmed the presence of the homozygous genotype of this p.Asn 370 Ser in the father DNA and the heterozygous one in the two children DNA. It has no detection of the 55 pb deletion in exon 9 among all the specimens of DNA treated. The mutation p.Asn 370 Ser is associated with Gaucher disease type 1 correlated of a total absence of neurological involvements.

[Diagnostic strategy of mucopolysaccharidosis type I in Tunisia]. / La mucopolysaccharidose de type I: stratégie diagnostique en Tunisie.

A Tunisian patient affected by mucopolysaccharidosis (MPS) was investigated for a biological analysis (quantitative and qualitative glycosaminoglycans (GAG) screening). We have also done an enzymatic determination of alpha-L-iduronidase activity (IDUA). The most common mutation (p.Gln 70 X, p.Trp 402X and p.Pro 533 Arg) were researched by an enzymatic restriction and sequencing of the IDUA gene. Enzymatic and urinary diagnostics suggested a MPS I phenotype. The patient investigated had the mutation p.Pro 533 Arg in the homozygous status, whereas his parents were heterozygous for this mutation.

[Mucopolysaccharidosis IVA (Morquio A syndrome): clinical, biological and therapeutic aspects]. / La mucopolysaccharidose IVA (syndrome de Morquio A): aspects clinique, biologique et thérapeutique.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is an autosomal recessive lysosomal storage disorder caused by a genetic deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS; E.C.3.1.6.4). GALNS is required to degrade keratan sulfate (KS) and chondroitine-6-sulfate (C6S). The accumulation of undegraded substrates in lysosomes of the affected tissues leads to a systemic bone dysplasia. Total urine glycosaminoglycans (GAG) in patients with MPS IVA are close to the normal range so it is difficult to distinguish this disease based on urine GAG excretion. Another potential disease marker could be KS levels in urine and plasma. Although the enzymatic diagnosis of affected patients with MPS IVA can be made, the detection of obligate heterozygotes by enzymatic measurement is less reliable because of a marked overlap of GALNS in fibroblasts or leucocytes from affected phenotype and normal controls. The genetic heterozygoty of MPS IVA has been facilitated by the isolation and characterization of the full lengh cDNA encoding human GALNS. Conventional therapy is symptomatic and limited to palliative procedures, which have virtually no impact upon mortality. To date, there is still no general consensus about the effectiveness of bone marrow transplantation. In the future, gene therapy could represent a great therapeutic improvement.

[Clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients]. / Etude de la maladie de Morquio A dans une famille tunisienne présentant deux enfants atteints.

Mucopolysaccharidosis type IV A (MPS IV A) is an autosomal recessive disorder resulting from the deficient activity of the lysosomal enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS) and the progressive lysosomal accumulation of keratane sulfate. Clinically, the MPS IV A differs from the other MPS by the localisation of the keratane sulfate in skelet and in eyes associated to the conservation of a normal intelligence. To date, the characterization and purification of the GALNS gene made a research for pathogenic mutations in patients with MPS IV A easier. These mutations are responsible of severe, intermediate or mild phenotype. The aim for this work was the research of clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients who were offsprings of consanguineous mating. Enzymatic and urinary diagnostics suggested a MPS IV A phenotype. A novel homozygous mutation IVS1+1G-A was identified by direct sequencing in the GALNS gene of the two patients. Identification of GALNS mutations provide genotype/phenotype correlations and permit the precision of anomalies responsible of Morquio A phenotype in concerned families.

Modulation of adipokines and cytokines in gestational diabetes and macrosomia.

CONTEXT/OBJECTIVE: Not much is known about the implication of adipokines and different cytokines in gestational diabetes mellitus (GDM) and macrosomia. The purpose of this study was to assess the profile of these hormones and cytokines in macrosomic babies, born to gestational diabetic women. DESIGN/SUBJECTS: A total of 59 women (age, 19-42 yr) suffering from GDM with their macrosomic babies (4.35 +/- 0.06 kg) and 60 healthy age-matched pregnant women and their newborns (3.22 +/- 0.08 kg) were selected. METHODS: Serum adipokines (adiponectin and leptin) were quantified using an obesity-related multiple ELISA microarray kit. The concentrations of serum cytokines were determined by ELISA. RESULTS: Serum adiponectin levels were decreased, whereas the concentrations of leptin, inflammatory cytokines, such as IL-6 and TNF-alpha, were significantly increased in gestational diabetic mothers compared with control women. The levels of these adipocytokines were diminished in macrosomic babies in comparison with their age-matched control newborns. Serum concentrations of T helper type 1 (Th1) cytokines (IL-2 and interferon-gamma) were decreased, whereas IL-10 levels were significantly enhanced in gestational diabetic mothers compared with control women. Macrosomic children exhibited high levels of Th1 cytokines and low levels of IL-10 compared with control infants. Serum IL-4 levels were not altered between gestational diabetic mothers and control mothers or the macrosomic babies and newborn control babies. CONCLUSIONS: GDM is linked to the down-regulation of adiponectin along with Th1 cytokines and up-regulation of leptin and inflammatory cytokines. Macrosomia was associated with the up-regulation of Th1 cytokines and the down-regulation of the obesity-related agents (IL-6 and TNF-alpha, leptin, and adiponectin).

Mucopolysaccharidosis type IV: N-acetylgalactosamine-6-sulfatase mutations in Tunisian patients.

Mucopolysaccharidosis type IVA (MPS IVA; OMIM #253000) or Morquio A syndrome is an autosomal recessive inborn error resulting from the deficient activity of the lysosomal enzyme, N-acetylgalactosamine-6-sulfatase (GALNS), and the progressive lysosomal accumulation of sulfated glycosaminoglycans. Clinically, the severe form of this lysosomal storage disease is characterized by a characteristic severe bone dysplasia and normal intelligence. To date, a variety of mutations have been associated with the severe MPS IVA phenotype. Here, we report the GALNS mutations in six severe MPS IVA patients from four unrelated Tunisian families. For mutation detection, each of the 14 exons and adjacent intron-exon junctions of the GALNS gene were sequenced after PCR-amplification from genomic DNA. Two novel mutations were identified: a G to A transition in the conserved 5' donor splice site of intron 1 (GACgt-->GACat: designated IVS1(+1g-->a)) and a G to C transversion in codon 66 of exon 2 predicting a glycine to arginine substitution (G66R). The IVS1(+1g-->a) mutation was homozygous in five similarly affected patients from three presumably unrelated families, but haplotype analysis suggested a common ancestor. The affected patient in the fourth family was homozygous for the G66R mutation. These are the first GALNS mutations causing severe MPS IVA disease identified in Tunisia. These molecular findings provide genotype/phenotype correlations, and permit accurate carrier detection, prenatal diagnosis, and counseling for MPS IVA disease in Tunisia where first cousin consanguineous mating remains frequent.

Mucopolysaccharidosis I: Alpha-L-Iduronidase mutations in three Tunisian families.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease resulting from the defective activity of the enzyme alpha-L-iduronidase (IDUA). The disease has severe and milder phenotypic subtypes. The IDUA mutations in five MPS I patients from three unrelated families from central and southern Tunisia were determined by amplifying and sequencing each of the IDUA exons and intron-exon junctions. Two novel IDUA mutations, c.1805delTinsGAACA in exon 13 and I270S in exon 7, and two previously reported mutations, P533R and R628X, were detected. The two patients in family 1 who had the Hurler phenotype were homoallelic for the novel deletion-insertion mutation. The patient in family 2 who also had the Hurler phenotype was heteroallelic for the novel missense mutation I270S and the previously reported nonsense mutation R628X. The two patients in family 3 who had the Hurler-Scheie phenotype were homoallelic for P533R. In addition, six known IDUA polymorphisms were identified. These are the first Tunisian MPS I patients to be genotyped. The identification of these mutations and their genotype-phenotype correlations should facilitate prenatal diagnosis and counselling for MPS I in Tunisia, where a very high rate of consanguinity exists.