[Fatal nutrient deficiencies after gastric bypass]. / Syndrome multicarentiel catastrophique post bypass gastrique.

INTRODUCTION: Bariatric surgery is a very effective treatment for obesity. After gastric bypass, micronutrient deficiencies frequently occur which can have dramatic consequences. CASE REPORT: We report the case of a 55-year-old woman who was admitted for psychomotor retardation, bilateral leg pitting edema and psoriasis-like rash that had been ongoing for 3 months. Pancytopenia, encephalopathy and heart failure rapidly occurred leading to multiorgan dysfunction syndrome and death. We retrospectively identified severe selenium deficiency with possible secondary cardiomyopathy, niacin deficiency resulting in pellagrous encephalopathy with skin lesions and gelatinous transformation of bone marrow. CONCLUSION: Micronutrient deficiency should systematically be assessed when new symptoms occur in a patient with a history of bariatric surgery. Selenium deficiency should be considered in the presence of any heart failure in this context.

Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis.

OBJECTIVES: Differential time to positivity of cultures of blood drawn simultaneously from central venous catheter and peripheral sites is widely used to diagnose catheter-related bloodstream infections without removing the catheter. However, the accuracy of this technique for some pathogens, such as Staphylococcus aureus, is debated in routine practice. METHODS: In a 320-bed reference cancer centre, the charts of patients with at least one blood culture positive for S. aureus among paired blood cultures drawn over a six-year period were studied retrospectively. Microbiological data were extracted from the prospectively compiled database of the microbiology unit. Data concerning the 149 patients included were reviewed retrospectively by independent physicians blinded to the absolute and differential times to positivity, in order to establish or refute the diagnosis of catheter-related sepsis. Due to missing data, 48 charts were excluded, so 101 cases were actually analysed. The diagnosis was established in 62 cases, refuted in 15 cases and inconclusive in the remaining 24 cases. RESULTS: For the 64 patients with both central and peripheral positive blood cultures, the differential positivity time was significantly greater for patients with catheter-related bloodstream infections due to S. aureus (P<0.02). However, because of the high number of false-negative cases, the classic cut-off limit of 120 min showed 100% specificity but only 42% sensitivity for the diagnosis of catheter-related bloodstream infection due to S. aureus. CONCLUSIONS: These results strongly suggest that despite its high specificity, the differential time to positivity may not be reliable to rule out catheter-related bloodstream infection due to S. aureus.

Diagnostic strategy for oncology patients with acute respiratory failure.

Acute respiratory failure (ARF) is frequent and often fatal in patients with a malignancy. However, there is not one type of "oncology patient", and it's high time that both clinical management and further studies consider specific populations rather than the heterogeneous and artificial group of "cancer patients". This individual-based approach will allow a relevant use of the numerous non invasive diagnostic tools developed during the past years: high resolution tomodensitometry, echocardiography, urine or serum antigen assays, polymerase chain reaction, serum biomarkers etc. These non invasive tools have reduced but not weakened the value of fiberoptic bronchoscopy and bronchoalveolar lavage: some subsets of patients may always benefit from this technique, particularly when new protective strategies such as non invasive mechanical ventilation and target-controlled infusion of sedative drugs are used. The present review focuses on the personalised approach required in "oncology patients" with ARF, based on first identifying the pattern of immunodeficiency, then listing the most probable hypotheses in the light of clinical and radiological findings in order to, finally, select the most accurate diagnostic tools.

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.

[Primary distal renal tubular acidosis]. / Acidose tubulaire rénale distale primitive.

Renal tubular acidosis are forms of metabolic acidosis characterized by an impairment of urinary acidification due to a lack of urine excretion of protons or loss of bicarbonates. Primary distal renal acidosis (dRTA) is characterized by hyperchloremic metabolic acidosis due to failure in proton excretion, variably severe nephrocalcinosis and/or nephrolithiasis associated with hypercalciuria and hypocitraturia. When the metabolic acidosis is compensated, dRTA can be diagnosed by the failure of urinary acidification after oral ammonium chloride or furosemide administration. dRTA is inherited as either an autosomal dominant or autosomal recessive trait. An autosomal dominant form results from a SLC4A1 gene mutation leading to dysfunction of the anionic exchanger type 1 (AE1). Otherwise, recessive forms are due to mutations of ATP6V1B1 gene encoding the B1-subunit of H+-ATPase expressed in the apical membrane of the alpha intercalated cells in collecting duct and in the cochlea. Those mutations lead to dRTA accompanied by sensorineural deafness. Also, mutations in ATP6V0A4 gene encode the accessory subunit a4 of the H+ATPase, leading to recessive forms of dRTA with preserved hearing or delayed signs of deafness. Molecular approach can identify mutations which are responsible for this pathology. The medical treatment is simple and involves an alkali load which allows curing the metabolic acidosis. Long-term outcome is usually good unless the patient's compliance is low or alkalizing treatment is insufficient.

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.

[Characteristics of encrustation of ureteric stents in patients with urinary stones]. / Caractéristiques des incrustations des endoprothèses urétérales chez les patients lithiasiques.

INTRODUCTION: The goal of this prospective study was to characterize ureteral stents encrustation in stone formers. MATERIAL AND METHODS: We report the results of a study based on 658 double-J stents (412 men and 246 women) collected from patients with in situ urinary calculi. The mean age was 48.2+/-16.0 years without differences between genders. Ureteral stent encrustation was analysed by infrared spectroscopy. Results are expressed according to the main component. RESULTS: The mean indwelling time was 73.5+/-73.2 days. The main component in stent encrustations was calcium oxalate (43.8%), essentially the monohydrate form (27.1%), followed by proteins (27.4%), calcium phosphates (16.4% with 8.4% brushite), and uric acid (5.2%). Struvite, detected on 49 stents, was the main component in 2.4% of cases. Significant differences according to gender and age were found: calcium oxalate monohydrate, which represented 24.5% in 20 to 29 years old men class increased to 37.0% in 50 to 59 years class and then decreased in older patients. Calcium oxalate dihydrate increased with age up to 70 years in women while it felt dramatically in man beyond 50 years old. Brushite was more abundant in young men (20.4% in patients aged 20-29 years) and was decreasing beyond this age while it remained in stable proportion for all age classes in women. Increasing prevalence of uric acid encrustations with age was observed, especially in men beyond the age of 70 years. Mineral encrustations increased with the indwelling time, the part of mineral being preponderant after 15 days: 7,3% of the stents had become massively encrusted within 113 days mean period. The comparison between biomaterials showed that silicone stents were significantly less encrusted than polyurethane stents. CONCLUSION: Stent encrustation constitutes a serious complication of ureteral stent use in stone formers. Lithogenic factors should be considered for the prevention of stent encrustation in these patients.

[2,8-dihydroxyadenine nephrolithiasis: from diagnosis to therapy]. / Lithiase de 2,8-dihydroxyadénine: du diagnostic à la prise en charge thérapeutique.

Adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency is an enzymopathy of purine metabolism, which is inherited as an autosomal recessive trait. APRT is a salvage enzyme that normally catalyzes the conversion of adenine to adenosine monophosphate. APRT deficiency results in adenine accumulation with oxidation by xanthine dehydrogenase (XDH; EC 1.1.1.204) to 2,8-dihydroxyadenine (2,8-DHA) then excreted in urine. This compound is extremely insoluble and its crystallization can lead to stone formation and renal failure. The diagnosis of the disease is based on stone analysis by infrared spectroscopy or microscopic examination of urine, which may reveal typical 2,8-DHA crystals. The enzyme activity measurements in erythrocyte lysates will identify both homozygotes and heterozygotes for APRT deficiency. Molecular approach can identify mutations which are responsible of this inherited disease. Two types of deficit are commonly distinguished, depending on the level of residual APRT activity: type I, mainly observed in Caucasian subjects, in whom the enzyme activity is undetectable in homozygous patients and type II, found in Japanese patients who are able to form APRT but the enzyme activity is strikingly reduced because a low affinity for phosphoribosylpyrophosphate. The crystallization of 2,8-DHA and subsequent renal damages may be prevented with allopurinol therapy, a xanthine oxidase inhibitor. The role of the laboratory is crucial to detect APRT deficiency and to assess the efficacy of therapy, the objective being to avoid 2,8-DHA crystal formation.

[Cystinuria: from diagnosis to follow-up]. / Cystinurie : du diagnostic à la surveillance thérapeutique.

Cystinuria is an autosomal recessive disorder characterized by an impaired transport of cystine and dibasic aminoacids, lysine, arginine and ornithine in the proximal renal tubule and in the epithelial cells of the gastrointestinal tract. Recurrent cystine nephrolithiasis is the main clinical feature. Mutations in SLC3A1 and/or SLC7A9 genes, which are encoding respectively the rBAT and the b(0,+)AT proteins of the amino acid transport system, are responsible of this disorder thus inducing a high dibasic amino acid excretion. Diagnostic is based on stone analysis by infrared spectroscopy or microscopic examination of urine which may reveal typical cystine crystals. Quantitative cystine excretion, which may be assessed by aminoacid chromatography, is higher in cystinic patients. Molecular approach can identify mutations which are responsible of this pathology. Medical treatment is mainly based on hydratation and urine alkalinisation, with the addition of thiol derivative only in refractory cases. Follow-up based on pH and specific gravity determination in urine samples and cystine crystal volume measurement are used to optimally monitor the medical treatment of cystinuric patients. Even with medical management, long-term outcome is poor due to insufficient efficacy and low patient compliance. Many patients suffer from renal insufficiency as a result of recurrent stone formation and repeated surgical procedures.

[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.

[Myelodysplastic syndrome / acute myeloid leukemia with t(8; 21) and bundle of Auer rods in neutrophils: an unusual hemopathy]. / Syndrome myélodysplasique / leucémie aiguë avec t(8;21) et polynucléaires à corps d'Auer en fagot: une hémopathie rare de présentation inhabituelle.

We report the case of a 8-year-old girl diagnosed with myelodysplastic syndrome. This case was morphologically characterized by the presence of bundle of Auer rods in the neutrophils. The evolution of the disease was marked by a quick transformation in a acute myeloid leukaemia with t(8;21) refractory to treatment. We reviewed the literature for clinical, biological and therapeutic features of this rare childhood hemopathy.