Rare cause of life-threatening hypercalcemia in an infant: a case report. / Cause rare d'hypercalcémie gravissime chez l'enfant : cas clinique

Background: 25-Hydroxyvitamin D 24-hydroxylase (CYP24A1) deficiency is a rare cause of autosomal recessive infantile hypercalcemia due to vitamine D hypersensitivity. Case presentation: We report the case of a 2-year-old boy who presented with severe hypercalcemia-hypercalciuria and a bilateral nephrocalcinosis. Laboratory investigations detected a collapsed parathormone and a highly elevated 1α,25-dihydroxycholecalciferol along with an increased phosphate excretion (hypophosphatemia and hyperphosphaturia). An adapted management with two courses of palmidronic acid and an eviction of vitamin D and calcium allowed to stabilize him. A homozygous p.Leu409Ser pathogenic variant on CYP24A1 gene resulting in a collapsed 25-Hydroxyvitamin D24-hydroxylase activity was found. A normal development is possible with a meticulous clinical, biological and nutritional management and monitoring. Conclusions: Vitamin D hypersensitivity is challenging during childhood, especially due to the need to avoid vitamin D while requiring a close nutritional monitoring to maintain a normal growth. Biomarkers such as vitamin D metabolite ratio and 24,25(OH)2D3 along with ionized calcium and nutritional management can contribute to properly follow patients with vitamin D hypersensitivity.

Contexte: Le déficit en 25-hydroxyvitamine D 24-hydroxylase (CYP24A1) est une cause rare d'hypercalcémie infantile autosomique récessive due à une hypersensibilité à la vitamine D. Présentation du cas: Nous rapportons le cas d'un garçon de 2 ans qui a présenté une hypercalcémie-hypercalciurie sévère et une néphrocalcinose bilatérale. Les examens de laboratoire ont détecté une parathormone effondrée et un 1α,25-dihydroxycholécalciférol très élevé ainsi qu'une excrétion accrue de phosphate (hypophosphatémie et hyperphosphaturie). Une prise en charge adaptée avec deux cures d'acide palmidronique et une éviction de la vitamine D et du calcium a permis de le stabiliser. Un variant pathogène homozygote p.Leu409Ser sur le gène CYP24A1 entraînant un effondrement de l'activité de la 25-hydroxyvitamine D24-hydroxylase a été retrouvé. Un développement normal est possible avec une prise en charge et un suivi clinique, biologique et nutritionnel méticuleux. Conclusions: L'hypersensibilité à la vitamine D est un défi pendant l'enfance, notamment en raison de la nécessité d'éviter la vitamine D tout en exigeant un suivi nutritionnel étroit pour maintenir une croissance normale. Les biomarqueurs tels que le rapport des métabolites de la vitamine D et la 24,25(OH)2D3, ainsi que le calcium ionisé et la gestion nutritionnelle peuvent contribuer à un suivi adéquat des patients souffrant d'hypersensibilité à la vitamine D.

[Troponin T cardiac analysis: clinical cases of the limits of its cardiospecificity]. / Illustrations cliniques d'un manque de cardiospécificité du dosage de troponine T hypersensible.

INTRODUCTION: Myositis are systemic diseases, in which heart damage is possible. Cardiac troponin T is often found to be defective to detect cardiac involvement. OBSERVATION: We report cases of two patients with a myositis. Diagnosis was retained based on muscle pain, increase in serum creatinine kinase, and inflammatory muscle damage on MRI. Histology confirmed the diagnosis for one of the two patients. Cardiac troponin T was measured in both patients, to detect myocardial involvement. Despite a serum elevation of this marker, cardiological assessment remained negative (electrocardiogram, cardiac ultrasound, cardiac MRI). Cardiac troponin I was normal in serum because of the absence of correlation with peripheral muscle involvement. CONCLUSION: Cardiac troponin T is correlated with muscle involvement in patients with myositis. Cardiac troponin I should be preferred because of a better specificity.

Performance of a quick pregnancy test on whole blood in early pregnancy units: a prospective cohort study.

OBJECTIVE: To assess the diagnostic performance of the NG-Test human chorionic gonadotropin (hCG) WB, which is a new point-of-care (POC) hCG whole-blood test. MATERIALS AND METHODS: This prospective study included women consulted in early pregnancy units for vaginal bleeding and/or pelvic pain with unknown pregnancy status after medical consultation including a pelvic ultrasound scan. A new POC test (the NG-Test hCG WB) and the usual laboratory serum test (considered the gold standard) were performed in patients. The results were interpreted in a blinded manner. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the NG-Test hCG WB. RESULTS: During the study period, 200 patients were included. The pregnancy rate was 17%. For the laboratory test, with a 5 UI/l hCG positivity threshold, the sensitivity, specificity, PPV, NPV, and Youden index of the NG-Test hCG WB were 89.7, 100, 100, 97.9, and 0.90%, respectively. Considering a 10 UI/l hCG positivity threshold, test sensitivity, specificity, PPV, NPV, and Youden index were 96.3, 100, 100, 99.3, and 0.96%, respectively. False-negative cases were either extremely brief pregnancies or residual hCG after miscarriage. The result was obtained within 5 min with the NG-Test hCG WB versus 90±31 min with the laboratory test. It was easy to use. CONCLUSION: The NG-Test hCG WB showed a high sensitivity, specificity, PPV, and NPV. Its use as triage in the case of a negative pelvic ultrasound exam is a potential strategy to improve patient flow, with an average time saving of 85 min.

Serum hCG threshold to assess medical abortion success.

OBJECTIVES: The main aim of the study was to establish a threshold for serum human chorionic gonadotropin (hCG) level that ruled out ongoing pregnancy after induced medical abortion (MA). The secondary aim was to discover risk factors for the need for uterine aspiration. METHODS: This prospective study included women who underwent MA with mifepristone-misoprostol at ≤9 weeks of gestation between 2012 and 2014. Serum hCG levels were measured 14-21 days after MA. The main outcome measure, ongoing pregnancy, was defined as the presence of an embryo with cardiac activity on transvaginal ultrasonography after MA. The receiver operating characteristic curve was plotted to determine the optimal serum hCG threshold. Risk factors for the need for uterine aspiration were calculated using multivariate logistic regression and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The study included 814 women. Mean gestational age was 46.5 ± 7.4 days for ongoing pregnancies and 44.2 ± 4.8 days for MA success (p = .43). The ongoing pregnancy rate after MA was 0.9%. A serum hCG threshold ≥900 IU/l to diagnose ongoing pregnancy gave 100% sensitivity and 81.5% specificity, compared with 85.7% sensitivity and 83.5% specificity using a threshold ≥1000 IU/l. Independent risk factors for uterine aspiration requirement were: gravidity (OR 3.8; 95% CI 1.1, 13.2; p = .001), gestational age >6 weeks (OR 6.0; 95% CI 1.8, 6.0; p = .006) and previous surgical abortion (OR 2.4; 95% CI 1.1, 5.2; p < .001). CONCLUSION: Serum hCG measurement <900 IU/l, 14-21 days after MA, is an efficient strategy for excluding ongoing pregnancy after first trimester MA.

Outcome of children treated with haematopoietic-stem cell transplantations from donors expressing the rare C77G variant of the PTPRC (CD45) gene.

The uncommon C77G polymorphism of the Protein-Tyrosine Phosphatase (PTPRC) gene (PTPRC; previously termed CD45) could confer an increased risk of immunopathology. This study compared the outcome of children following human leucocyte antigen-matched unrelated haematopoïetic-stem cell transplantations (HSCT) from donors carrying (C77G cases: n = 8) or not (controls: n = 36) the PTPRC C77G polymorphism. Transmission of the PTPRC C77G polymorphism through the graft was suggested by unusual CD45RA phenotype in the donors and/or in the recipients after, but not before HSCT. Restriction-Fragment Length Polymorphism and sequencing confirmed the polymorphism. Overall survival rates were similar in C77G cases and controls (63% vs. 61%). Acute leukaemia relapse tended to be less frequent in C77G cases (0% vs. 32%; P = 0·09). Among recipients surviving ≥ 30 d, acute GVHD (aGVHD) ≥ grade 2 tended to be more frequent (100% vs. 58%; P = 0·07) and the rate of steroid-refractory or -dependant aGVHD higher (67% vs. 28%) in C77G cases. Finally, extensive chronic GVHD tended to occur more frequently (40% vs. 9%) in C77G cases. Recovery of lymphocyte subsets and virus-specific CD4 was similar in C77G cases and controls while interleukin 2 (IL2)-responses through CD3 stimulation were higher in C77G cases (P = 0·004). In conclusion, HSCT from PTPRC C77G donors could increase GVHD risk without compromising overall survival. Altered IL2-responses could be involved in this process.

Quantitative and qualitative CD4 T cell immune responses related to adenovirus DNAemia in hematopoietic stem cell transplantation.

The nature of adenovirus (AdV)-specific T cells that could best predict the capacity of immunocompromised host to fight AdV is unclear. To this aim, 47 pediatric patients were enrolled for at least 3 months either at allogeneic bone marrow transplantation (BMT) (23 genoidentical, 18 unrelated of which 9 were 10/10 and 9 were 9/10 HLA-matched) or at unrelated cord blood transplantation (n = 6). Enumeration of AdV-specific CD4 T cells secreting cytokines (flow cytometry) and proliferative responses to AdV ((3)HT-incorporation) were compared to AdV-DNAemia. A total of 44/47 patients did not evidence AdV-DNAemia. Thirty-two of 44 (73%) developed CD4-mediated interferon-gamma (IFN-γ) responses to AdV (median 0.36 CD4/µL of blood) since the first month post-HSCT (n = 11: 8 genoidentical and 3 unrelated) or the third month (n = 21 additional patients). At 3 months, both incidence and level intensities of AdV-specific CD4 appeared similar in genoidentical and unrelated BMT (70% and 80%; 0.36 and 0.21 CD4/µL, respectively) and not statistically different from age-matched controls (76%; 1.35 CD4/µL), whereas cord blood transplanted patients exhibited similar incidence but higher level intensities (67%; 1.49 CD4/µL). Polyfunctional (IL2 + IFN-γ) and proliferative responses appeared later, after the third month. Three of 4 9/10 HLA-matched unrelated HSCT that did not develop immunity to AdV presented chemotherapy-resistant AdV-DNAemia at 3 to 5 months post-hematopoietic stem cell transplantation (HSCT). Two were successfully treated with AdV-specific CTL infusion. Monitoring, since month 1 post-HSCT, of IFN-γ-secreting AdV-specific CD4 appears suitable for early detection of at-risk patients especially in 9/10 HLA-matched unrelated HSCT and preferable to monitoring of more delayed IL2- and proliferative responses.