Anya Rothenbuhler - Profile on Academia.edu (original) (raw)

Papers by Anya Rothenbuhler

Annals of the Rheumatic Diseases, Jun 1, 2015

Objectives: We investigated whether the RDW could be a differential marker for adult onset still'... more Objectives: We investigated whether the RDW could be a differential marker for adult onset still's disease (AOSD) from sepsis in the early phase. Methods: We retrospectively reviewed the medical records of 12 patients with AOSD, 28 patients with sepsis and 30 healthy controls. Laboratory data of patients were collected on the first day of hospitalization. All subjects in patient groups performed microbial tests to confirm or exclude sepsis. And data of healthy controls were collected one time at medical check-up visit. Results: The RDWs of patients with AOSD and sepsis were elevated than controls. There were no significant differences in white blood cell counts, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between AOSD and sepsis group. However, the RDW of sepsis group was significantly elevated than that of AOSD group by Mann-Whitney's U analysis (p=0.042) as shown in Figure . Proportion of patients with abnormal RDW level (above 14.5%) in sepsis group (15/28 (53.5%)) was higher than in AOSD group (3/12 (25.0%)). However, the RDW was not a significant independent factor for discriminating sepsis from AOSD in the multivariate regression analysis. Conclusions: The RDW was elevated in patients with AOSD and with sepsis. And it was elevated significantly higher in sepsis than in AOSD. So we suggest that the RDW might be a differential marker between AOSD and sepsis. [1] Dabbah S, Hammerman H, Markiewicz W, et al. Relation between red cell distribution width and clinical outcomes after acute myocardial infarction. Am

Cranial synostosis and Chiari 1 malformation in X-linked hypophosphatemic rickets

Bone Abstracts, Jul 11, 2017

Determinants of Final Height in Patients Born Small for Gestational Age Treated with Recombinant Growth Hormone

Hormone Research in Paediatrics, 2021

Introduction: About 8% of children born small for gestational age (SGA) do not reach a final heig... more Introduction: About 8% of children born small for gestational age (SGA) do not reach a final height within the normal range. Recombinant human growth hormone (rhGH) has been shown to be effective in increasing the final height in children born SGA. Our objective was to identify predictive factors of final height in children born SGA treated with rhGH. Materials and Methods: In this retrospective study, conducted in a tertiary pediatric endocrinology referral center, we recruited all patients born SGA (defined as birth length or weight <10th percentile) treated with rhGH for more than 12 months for whom final height data were available. Some patients had received gonadotropin-releasing hormone (GnRH) analog therapy. Results: We included 252 patients with an average birth length of −2.0 ± 0.7 SD and birth weight of −1.7 ± 1.0 SD. After 4.6 ± 2.8 years of rhGH treatment, their height increased from −2.2 ± 0.9 SD to −1.5 ± 0.9 SD. In multivariate analysis, we identified 8 factors that predict 46% of the final height, namely, cause of SGA (p < 0.0001), GnRH analog therapy >2 years (p = 0.006), birth length (p < 0.02), height at the start of rhGH (p < 0.0001), IGF-1 level at the start of rhGH (p = 0.0002), growth velocity during the 1st year of treatment (p = 0.0002), and age and height at the onset of puberty (p < 0.0001, p = 0.0007, respectively). Conclusion: In this large cohort of SGA patients who had reached their final height, we were able to confirm that growth hormone increases final height in short SGA children. In addition, we identified several factors associated with a better response to growth hormone treatment.

Clinical picture of early infancy PTH-resistance syndromes: is it time to improve diagnostic criteria?

Endocrine Abstracts, May 2, 2023

European Journal of Orthodontics, Nov 7, 2019

Background: Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3-1/... more Background: Pseudohypoparathyroidism (PHP, OMIM #103580) is a very rare disease (incidence 0.3-1/100,000). Heterozygous inactivating mutations involving the maternal GNAS exons 1-13 that encodes the alpha subunit of the stimulatory G protein (Gsα) cause inactivating parathyroid hormone (PTH)/PTHrP signalling disorder type 2 (iPPSD2 or PHP type 1A), which is characterized by Albright hereditary osteodystrophy and resistance to multiple hormones that act through the Gsα signalling pathway (including PTH, thyroid-stimulating hormone, and α-melanocyte-stimulating hormone). To date, little information is available on craniofacial features in patients with PHP. The small number of patients studied in previous reports as well as the lack of molecular characterization of the patients may have precluded the detection of specific orofacial manifestations in the different PHP subtypes. Materials/Methods: We conducted a systematic analysis of dental and craniofacial features in 19 patients with iPPSD2 and maternal GNAS inactivating mutations to assess the frequency and specificity of the anomalies. Results: Facial examinations showed reduced vertical, sagittal, and transverse development of the mid-facial structures. Intraoral and radiographic examinations revealed that 89 per cent of the patients had at least one dental anomaly, including tooth submergence leading to severe infraocclusion in 83 per cent of cases. Craniofacial analysis of lateral cephalometric radiographs also showed a significant alteration in the development of the cranial base and maxillary and mandibular structures in these patients. Conclusions: Patients with iPPSD2 and maternal GNAS mutations had specific craniofacial alterations and dental abnormalities. These specific defects should be assessed in order to provide appropriate dental and orthodontic care to these patients. (clinical trial registration: 1920371 v 0, French Nationale Data Processing and Liberties Commission -CNIL).

Decrease in clinical hypoglycemia in young children with type 1 diabetes treated with free-mixed aspart and detemir insulin: an open labeled randomized trial

Pediatric Diabetes, Aug 1, 2015

To compare the effectiveness of a free-mix of aspart (A) and detemir (D) insulins (ADIM) with a c... more To compare the effectiveness of a free-mix of aspart (A) and detemir (D) insulins (ADIM) with a commonly used premixed fixed-ratio aspart and neutral protamine Hagedorn (NPH) insulin mixture (ANIM) in young children with type 1 diabetes (T1D) treated with twice-daily injections. The trial thus compares not only D vs. NPH, but also flexible, personalized insulin preparations vs. a fixed premixed preparation. This single-center, open-label, randomized trial included 82 children with T1D. Patients stayed on ANIM for 1 yr of optimization of disease management, then were randomized to either ANIM (N = 41) or ADIM (N = 41) for another year. Frequency of severe or symptomatic episodes, glycated hemoglobin A1c (HbA1c), and blood glucose (BG) values. Compared with ANIM, ADIM decreases symptomatic hypoglycemia by approximately 2 fold (p < 0.001) and severe hypoglycemia by 7-10 fold (p = 0.04). ADIM somewhat reduced BG variation. Mean HbA1c was comparable on ADIM (7.9 ± 0.8 %; 63 ± 9 mmol/mol) and ANIM (8.2 ± 0.7 %; 66 ± 8 mmol/mol). Using a free-mixing preparation of aspart and detemir insulin decreases hypoglycemia in young children with type 1 diabetes.

Hormone Research in Paediatrics, 2017

Objective: X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets... more Objective: X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Study Design: Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. Results: On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal <1.5), being >1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. Conclusions: MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity.

Facteurs associés à l’apparition d’enthésopathies au cours de l’hypophosphatémie liée à l’X

Revue du Rhumatisme, Dec 1, 2021

Development of spinal enthesopathies in adults with X-linked hypophosphatemia

The Journal of Clinical Endocrinology and Metabolism, Jun 30, 2023

Context Musculoskeletal complications are the main manifestations in adults with X-linked hypopho... more Context Musculoskeletal complications are the main manifestations in adults with X-linked hypophosphatemia (XLH). Enthesopathy significantly impairs quality of life. Objective To identify the risk factors associated with the development and progression of spinal enthesopathies in adults with XLH. Design and setting We conducted a retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism. Patients Adults XLH patients with 2 EOS® imaging performed at least 2 years apart at the same center between June 2011 and March 2022. The progression of enthesopathies was defined as a new enthesopathy at least 1 intervertebral level in patients with or without presence of enthesopathy at baseline. Main outcome measures Demographic, treatment, PHEX mutation with the progression of enthesopathies. Results Fifty-one patients (66.7% of women, mean age 42.1 ± 13.4 years) underwent 2 EOS imaging with an average interval of 5.7 (± 2.31) years. Progression of spinal enthesopathies was observed in 27 (52.9%) patients. In univariate analysis, patients with a progression of spinal enthesopathies were significantly older (P < .0005), were significantly older at treatment initiation (P = .02), presented with dental complications (P = .03), received less frequently treatment during childhood with phosphate and/or vitamin D analogs (P = .06), and presented more frequently with hip osteoarthritis (P = .002) at baseline. In multivariate analysis, none of these factors was associated with a progression of spinal enthesopathies. Conclusion This study confirms the high proportion of patients with a progression of spinal enthesopathies. Age seems to be the main factor associated with progression.

The Journal of Clinical Endocrinology and Metabolism, Apr 25, 2023

Background: Pseudohypoparathyroidism (PHP) and related disorders newly referred to as inactivatin... more Background: Pseudohypoparathyroidism (PHP) and related disorders newly referred to as inactivating PTH/PTHrP signaling disorders (iPPSD) are rare endocrine diseases. Many clinical features including obesity, neurocognitive impairment, brachydactyly, short stature, parathyroid hormone (PTH) resistance, and resistance to other hormones such as thyroid-stimulating hormone (TSH) have been well described, yet they refer mainly to the full development of the disease during late childhood and adulthood. Objective: A significant delay in diagnosis has been reported; therefore, our objective is to increase awareness on neonatal and early infancy presentation of the diseases. To do so, we analyzed a large cohort of iPPSD/PHP patients. We included 136 patients diagnosed with iPPSD/PHP. We retrospectively collected data on birth and investigated the rate of neonatal complications occurring in each iPPSD/PHP category within the first month of life. Results: Overall 36% of patients presented at least one neonatal complication, far more than the general population; when considering only the patients with iPPSD2/PHP1A, it reached 47% of the patients. Neonatal hypoglycemia and transient respiratory distress appeared significantly frequent in this latter group, ie, 10.5% and 18.4%, respectively. The presence of neonatal features was associated with earlier resistance to TSH (P < 0.001) and with the development of neurocognitive impairment (P = 0.02) or constipation (P = 0.04) later in life. Our findings suggest that iPPSD/PHP and especially iPPSD2/PHP1A newborns require specific care at birth because of an increased risk of neonatal complications. These complications may predict a more severe course of the disease; however, they are unspecific which likely explains the diagnostic delay.

X-linked hypophosphatemia, obesity and arterial hypertension: data from the XLH21 study

Pediatric Nephrology, Jun 27, 2022

Patients with mutations in PHEX or FGF23 share FGF23 excess but present distinct bone and mineral metabolism features

Bone Abstracts, Jun 1, 2013

Growth patterns and outcomes of growth hormone therapy in patients with acrodysostosis

Journal of Endocrinological Investigation, Feb 7, 2023

Burosumab and Dental Abscesses in Children With X‐Linked Hypophosphatemia

JBMR plus, Sep 20, 2022

ABSTRACTX‐linked hypophosphatemia (XLH) is a rare genetic disorder that disrupts skeletal and den... more ABSTRACTX‐linked hypophosphatemia (XLH) is a rare genetic disorder that disrupts skeletal and dental mineralization. In addition to rickets in children, XLH patients also have frequent spontaneous dental abscesses that increase the risk of tooth loss and may lead to facial cellulitis. Hypomineralized and hypoplastic dentin is the main driver of these infections. Conventional treatment (CT) of XLH improves this tissue defect and reduces the occurrence of dental abscesses. Burosumab is a recent treatment for XLH that targets excess circulating fibroblast growth factor 23 (FGF23), and its benefits on rickets have been demonstrated. It is not yet known whether burosumab improves dental manifestations of XLH. The main objective of our study was to compare the incidence of dental abscesses with XLH treated with either CT or burosumab. In this monocentric retrospective study, we measured and compared the incidence of dental abscess in children with XLH treated with either CT or burosumab, followed at our dental center for at least 1 year. The primary endpoint was the number of dental abscesses per month of dental follow‐up. A total of 71 children were included in the study, with a mean ± standard deviation (SD) age at the start of dental follow‐up of 7.86 ± 3.76. Thirty‐eight children were treated with CT (53.5%) and 33 with burosumab (46.5%). All children treated with burosumab had previously been treated with CT. The mean number of dental abscesses per month of dental follow‐up was significantly reduced in the burosumab group compared with the CT group (0.01 versus 0.04; p = 0.04). Burosumab treatment appears to be associated with a reduction in the number of dental abscesses in XLH children, compared with CT. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Calcified Tissue International, Jul 31, 2017

Several FGF23 immunoassays are available. However, they are reserved for research purposes as non... more Several FGF23 immunoassays are available. However, they are reserved for research purposes as none have been approved for clinical use. We evaluated the performances of a new automated assay for intact FGF23 on the DiaSorin Liaison platform which is approved for clinical use. We established reference values in 908 healthy French subjects aged 18-89 years, and measured iFGF23 in patients with disorders of phosphate metabolism and in patients with chronic kidney disease (CKD). Intra-assay CV was 1.04-2.86% and inter-assay CV was 4.01-6.3%. The limit of quantification was \10 ng/L. Serum iFGF23 concentrations were considerably lower than EDTA values highlighting the importance of using exclusively EDTA plasma. Liaison iFGF23 values were approximately 25% higher than Immutopics values. In the 908 healthy subjects, distribution of the Liaison iFGF23 values was Gaussian with a mean ± 2SD interval of 22.7-93.1 ng/L. Men had a slightly higher level than women (60.3 ± 17.6 and 55.2 ± 17.2 ng/L, respectively). Plasma iFGF23 concentration in 11 patients with tumour-induced osteomalacia, 8 patients with X-linked hypophosphatemic rickets, 43 stage 3a, 43 stage 3b, 43 stage 4, 44 stage 5 CKD patients, and 44 dialysis patients were 217.2 ± 144.0, 150.9

Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypophosphatemia

Journal of Dental Research, Nov 13, 2016

X-linked hypophosphatemia (XLH) is a rare genetic skeletal disease where increased phosphate wast... more X-linked hypophosphatemia (XLH) is a rare genetic skeletal disease where increased phosphate wasting in the kidney leads to hypophosphatemia and prevents normal mineralization of bone and dentin. Here, we examined the periodontal status of 34 adults with XLH and separated them according to the treatment they received for hypophosphatemia. We observed that periodontitis frequency and severity were increased in adults with XLH and that the severity varied according to the hypophosphatemia treatment. Patients who benefited from an early and continuous vitamin D and phosphate supplementation during their childhood presented less periodontal attachment loss than patients with late or incomplete supplementation. Continued hypophosphatemia treatment during adulthood further improved the periodontal health. Extracted teeth from patients with late or incomplete supplementation showed a strong acellular cementum hypoplasia when compared with age-matched healthy controls. These results show that XLH disturbs not only bone and dentin formation but also cementum and that the constitutional defect of the attachment apparatus is associated with attachment loss.

Hormone Research in Paediatrics, 2020

Tujuan Untuk mengidentifi kasi faktor-faktor prediksi dan biomarker dalam perkembangan lesi praka... more Tujuan Untuk mengidentifi kasi faktor-faktor prediksi dan biomarker dalam perkembangan lesi prakanker leher rahim atau neoplasia serviks intraepitel (CIN).

Joint Bone Spine, Nov 1, 2019

X-linked hypophosphatemia (XLH), due to a PHEX gene mutation, is the most common genetic form of ... more X-linked hypophosphatemia (XLH), due to a PHEX gene mutation, is the most common genetic form of rickets and osteomalacia. Manifestations in children consist of rickets, lower-limb bone deformities, bone pain, failure to thrive, dental abscesses, and/or craniostenosis. Adults may present with persistent bone pain, early osteoarthritis, hairline fractures and Looser zones, enthesopathy, and/or periodontitis. Regardless of whether the patient is an infant, child, adolescent or adult, an early diagnosis followed by optimal treatment is crucial to control the clinical manifestations, prevent complications, and improve quality of life. Treatment options include active vitamin D analogs and phosphate supplementation to correct the 1,25(OH) 2 vitamin D deficiency and to compensate for the renal phosphate wasting, respectively. The recently introduced FGF23 antagonist burosumab is designed to restore renal phosphate reabsorption by the proximal tubule and to stimulate endogenous calcitriol production. In Europe, burosumab is licensed for use in pediatric patients older than 1 year who have XLH. This review discusses the diagnosis and treatment of XLH and describes the indications of the various available treatments.

Imaging patterns in pediatric hypophosphatasia

Pediatric Radiology, Dec 2, 2021

Hypophosphatasia is a rare genetic disorder of calcium and phosphate metabolism due to ALPL gene ... more Hypophosphatasia is a rare genetic disorder of calcium and phosphate metabolism due to ALPL gene mutations, which leads to abnormal mineralization of the bones and teeth. Hypophosphatasia is characterized by low serum alkaline phosphatase activity and a number of clinical signs, including failure to thrive, bone pain and dental issues. The diagnosis is suspected based on clinical, laboratory and imaging findings and confirmed by genetic testing. Diagnosis in children is often delayed due to a lack of disease awareness, despite specific imaging findings that are a cornerstone of the diagnosis. The recent approval of enzyme replacement therapy (bone-targeted recombinant tissue nonspecific alkaline phosphatase) has given imaging an important role in monitoring treatment efficacy. The aim of this pictorial essay is to review the imaging features of hypophosphatasia at diagnosis and during follow-up, including whole-body magnetic resonance imaging patterns.