Background/aim X-linked hypophosphatemia (XLH) is a rare disease characterized by low phosphate levels. Scientific evidence points to a link between hypophosphatemia and obesity in general ...population. The aim of our longitudinal observational study was to investigate the prevalence of obesity and associated factors in a large cohort of children with XLH. Patients/methods We studied 172 XLH-children 5–20 years of age (113 girls/59 boys). Anthropometric parameters (weight, height, and BMI) were collected at birth and during follow-up at mean ages of 5.3, 8.2, 11.3, and 15.9 years (groups 1, 2, 3, and 4, respectively). In each group, subjects were classified based on International Obesity Taskforce (IOTF) cut off values of BMI for age and sex as overweight or obese (IOTF 25–30 or ≥30 kg/m2, respectively). Results In each age-group, almost 1/3 of XLH-patients were classified as overweight or obese (29.4, 28.7, 27.5, and 36.7% in groups 1, 2, 3, and 4, respectively). Children without a XLH-family history had higher BMI-IOTF at every point of follow-up, compared to those with positive XLH-family history. Similarly, higher BMI-IOTF was significantly associated with treatment duration (23.3 ± 4.4 vs 23.8 ± 3.8 vs 25.2 ± 4.5 kg/m2, for subjects with treatment duration of <5, 5–10 and >10 years, respectively, P for trend = 0.025). Multiple regression analysis confirmed an association of treatment duration and lack of XLH-family history with higher BMI-IOTF. Conclusion One out of three of XLH-children have phenotypically unfavourable metabolic profile expressed as increased prevalence of overweight or obesity in comparison to general population. Both the lack of XLH family history and the duration of treatment increase the risk of higher BMI-IOTF. BMI should be carefully monitored in children, and later in adults, with XLH.
Methods A convenience retrospective study analysed 10 female and 4 male patients with EoE being treated according to dietary therapy recommendations, during the phase of progressive reintroduction of ...eliminated foods following the 6-food elimination diet period.
To investigate whether low-dose mitotane (up to 2 g/day) could be a temporary therapeutic alternative to transsphenoidal surgery (TSS) in pediatric Cushing’s disease (CD). Twenty-eight patients with ...CD aged 12.2 years (± 2.2) were referred to our center. We compared nine patients treated with mitotane alone for at least 6 months to 13 patients cured after surgery. Primary outcomes were changes in growth velocity, BMI and pubertal development. The following results were obtained: (1) Mitotane improved growth velocity z-scores (−3.8 (±0.3) vs −0.2 (±0.6)), BMI z-scores (2.1 (±0.5) vs 1.2 (±0.5) s.d.) and pubertal development. After 1 year on mitotane, the mean BMI z-score was not significantly different in both groups of patients. (2) Control of cortisol secretion was delayed and inconsistent with mitotane used as monotherapy. (3) Side effects were similar to those previously reported, reversible and dose dependent: unspecific digestive symptoms, concentration or memory problems, physical exhaustion, adrenal insufficiency and hepatitis. (4) In one patient, progressive growth of a pituitary adenoma was observed over 40 months of mitotane treatment, allowing selective adenomectomy by TSS. In conclusions, low-dose mitotane can restore growth velocity and pubertal development and decrease BMI in children with CD, even without optimal control of cortisol secretion. It may promote pituitary tumor growth thus facilitating second-line TSS. However, given its possibly life-threatening side effects (transient adrenal insufficiency and hepatitis), and in the absence of any reliable follow-up procedures, this therapy may be difficult to manage and should always be initiated and monitored by specialized teams.
Objective To assess the growth promoting effect of a recombinant growth hormone (rGH) treatment protocol adjusted on insulin-like growth factor 1 (IGF-1) dosing in children affected by the most ...severe forms of FGFR3 N540K-mutated hypochondroplasia. Study design Midterm results of an open-label, single-center, nonrandomized, 2003-2020 pilot trial to final stature, including 6 children (mean age, 2.6 ± 0.7 years; mean height SDS, −3.0 ± 0.5) with the N540K mutation of FGFR3 gene who received an rGH dosage titrated to an IGF-1 level close to 1.5 SDS of the normal range. rGH therapy was interrupted 1 day per week, 1 month per year, and 6 months every 2 years. Results The mean height SDS increased by 1.9 during the 6.1 ± 0.9-year study period, reaching −0.8 to −1.3 at age 8.7 ± 1 years. The mean ± SDS baseline IGF-1 value was −1.6 ± 0.5 before rGH treatment and 1.4 ± 0.3 during the last year of observation. The average cumulative rGH dose was 0.075 ± 0.018 mg/kg/day (range, 0.059-0.100 mg/kg/day). Trunk/leg disproportion was improved. Conclusion IGF-1–dosing rGH treatment durably improves growth and reduces body disproportion in children with severe forms of hypochondroplasia.
Background: Hypocalcemia carries a risk of cardiac conduction incidents and death. Hypocalcemia is a frequent adverse effect of pamidronate.
Objective: The objective of this study was to investigate ...whether pamidronate infusion lengthens the ventricular repolarization in children.
Design and Methods: Thirty-four children with cerebral palsy and severe osteoporosis were treated for approximately 1 yr with pamidronate (three times per year). Calcemia and corrected QT interval (QTc) (in which the QT interval is a measure between the Q and T waves in the electrical cycle of the heart) were measured before and after each cycle of intravenous infusions.
Results: Pamidronate decreased calcemia in all patients from 2.40 to 2.21 mm (P < 0.0001) and increased QTc from 390 to 403 ms (P < 0.0001), with 7.4% of postinfusion QTc becoming longer than 440 ms. QTc at baseline was significantly correlated to final QTc (P < 0.0001; r2 = 0.27).
Conclusions: Because we observed a lengthening in QTc after bisphosphonate infusion, we recommend that children treated with pamidronate should receive attention as to other possible risk factors of prolonged QT and have a preinfusion and postinfusion measurement of their QTc.
It is recommended that children treated with pamidronate should receive attention as to other possible risk factors of prolonged QT and have a pre- and post-infusion measurement of their QTc.
Objective To evaluate bone mineral density (BMD) in children with Cushing disease before and after transphenoidal surgery (TSS). Study design Hologic dual-energy x-ray absorptiometry (DXA) scans of ...35 children with Cushing disease were analyzed retrospectively. Sixteen of the 35 patients had follow-up DXA scans performed 13 to 18 months after TSS. BMD and bone mineral apparent density (BMAD) for lumbar spine (LS) L1 to L4 and femoral neck (FN) were calculated. Results Preoperatively, 38% and 23% of patients had osteopenia of the LS and FN, respectively. Both BMD and BMAD Z-scores of the LS were worse than those for the FN (–1.60 ± 1.37 versus –1.04 ± 1.19, P = .003), and (–1.90 ± 1.49 versus –0.06 ± 1.90, P < .001); postoperative improvement in BMD and BMAD were more pronounced in LS than in the FN (0.84 ± 0.88 versus 0.15 ± 0.62, P <.001; and 0.73 ± 1.13 versus –0.26 ± 1.21, P = .015). Pubertal stage, cortisol levels, and length of disease had no effect on BMD. Conclusions In children with Cushing disease, vertebral BMD was more severely affected than femoral BMD and this effect was independent of degree or duration of hypercortisolism. BMD for the LS improved significantly after TSS; osteopenia in this group may be reversible.
Early diagnosis, optimal therapeutic management and regular follow up of children with X-linked hypophosphatemia (XLH) determine their long term outcomes and future quality of life. Biochemical ...screening of potentially affected newborns in familial cases and improving physician's knowledge on clinical signs, symptoms and biochemical characteristics of XLH for de novo cases should lead to earlier diagnosis and treatment initiation. The follow-up of children with XLH includes clinical, biochemical and radiological monitoring of treatment (efficacy and complications) and screening for XLH-related dental, neurosurgical, rheumatological, cardiovascular, renal and ENT complications. In 2018, the European Union approved the use of burosumab, a humanized monoclonal anti-FGF23 antibody, as an alternative therapy to conventional therapy (active vitamin D analogues and phosphate supplements) in growing children with XLH and insufficiently controlled disease.
Diagnostic criteria of XLH and the principles of disease management with conventional treatment or with burosumab are reviewed in this paper.
Si La vitamine D est connue depuis près d’un siècle pour son action antirachitique, depuis quelques années de nombreux travaux mettent en évidence l’implication de la vitamine D dans le développement ...des maladies auto-immunes (psoriasis, asthme, diabète de type 1...), sensibilité au virus (tuberculose, grippe, bronchiolite...) ou de cancers. La forme active de la vitamine D, la 1,25-(OH)2D joue un rôle immunomodulateur complexe associant : (1) une activation des systèmes non spécifiques de défense immunitaire, en favorisant la différenciation et les activités cytotoxiques des monocytes-macrophages; et (2) une inhibition des systèmes de défense immunitaire antigènes-spécifiques, en diminuant la fonction de présentation des antigènes des monocytes, en modulant la prolifération et les activités des lymphocytes T et B, et en favorisant le maintien ou la restauration de la fonction immunosuppressive des lymphocytes. Ces actions permettent d’expliquer les effets préventifs de la 1,25-(OH)2D sur le développement des maladies auto-immunes ou le rejet des hétérogreffes chez l’animal. La synthèse d’analogues ayant les mêmes activités immunomodulatrices que la 1,25-(OH)2D, tout en étant moins hypercalcémiants, ouvre des perspectives intéressantes pour cette prévention en clinique humaine. La question qui reste ouverte porte sur les niveaux de vitamine D à recommander car les niveaux de vitamine D (25(OH)D) nécessaire pour observer ce rôle protecteur sont beaucoup plus élevés que les niveaux pour maintenir une santé osseuse optimale. Il faudrait largement augmenter les supplémentations. Toute la difficulté réside dans le fait que ces supplémentations élevées peuvent s’associer à des signes d’hypercalcémie. L’autre question est « qui supplémenter » : à quel âge, à quelle dose ?
Adults with X-linked hypophosphatemia (XLH) may suffer from skeletal symptoms leading to functional disability. No data on their quality of life (QoL) have been reported so far. Our objectives were ...to evaluate the QoL and its determinants in XLH adults.
We conducted a prospective study in XLH adults, who consulted for musculoskeletal symptoms between 2013 and 2014. We assessed their QoL using HAQ, RAPID3 and SF36, and analysed the variables associated with low QoL. We compared their QoL to that of patients affected with axial spondyloarthritis (ax-SpA) (paired on age and gender), a rheumatologic disorder with a known low QoL.
Fifty-two XLH adults (37 women (71.1%); mean age 41.8±13.3 years) were included; 44 (84.6%) patients had an altered QoL. Increased age and presence of structural lesions were significantly associated with worse QoL (HAQ, RAPID3) (P<0.05). Presence of enthesopathies was significantly associated with worse RAPID3 (OR=4.45 (1.09-18.29), P=0.038). Treatment with phosphate supplements and vitamin D in XLH adults were significantly associated with a better SF36-mental component score (OR=0.14 (0.03-0.57), P=0.007 and OR=0.26 (0.07-0.98), P=0.047 respectively). QoL was significantly worse in XLH than in ax-SpA adults (VAS pain, SF36-PCS, RAPID3) (P<0.05).
Our study showed i) QoL of XLH adults is altered and significantly worse than that of ax-SpA patients (VAS pain, SF36-PCS and RAPID3), ii) structural lesions and especially enthesopathies are associated with a worse QoL and iii) treatment using phosphate supplements and/or vitamin D is associated with a better mental health score.
Context: Twin and family studies indicate that genetic factors contribute to the variability of age at menarche (AAM), a multifactorial trait of major importance to human reproductive success. ...Individual variability of premenarcheal fatness is known to be an important determinant of AAM.
Objective: The objective of the study was mapping quantitative trait loci (QTLs) for AAM.
Design and Methods: AAM was assessed in 98 sister pairs of recent European ancestry whose growth charts were available. There was a negative correlation between menarcheal body weight sd score (SDS) and AAM (r = 0.47, P < 0.0001). We designed a genome scan approach and used the variance components model implemented in Merlin for quantitative traits to evaluate linkage of AAM and AAM adjusted for menarcheal weight SDS to 418 genome-wide microsatellites.
Results: Multipoint linkage analysis for AAM revealed nominal QTLs defined by LOD scores between 1.06 and 1.69 on chromosomes 1p, 1q, 7p, 8q, 16p, 19q, and 20q. The genome scan for AAM adjusted for menarcheal weight SDS revealed several QTLs with strongly suggestive LOD scores in 16q21 (LOD = 3.33), 16q12 (LOD = 3.12), and 8p12 (LOD = 2.18) and a number of other nominally significant QTLs yet viewed as hypothetical.
Conclusions: We found several regions that may contain determinants of AAM, but there is still a long series of steps to confirm these QTLs and identify the genomic polymorphisms implicated in AAM variability.
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