Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation
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Ayfer Alikasifoglu
,
Yagmur Unsal
,
Elmas Nazli Gonc
Abstract
Objectives
Hereditary hypophosphatemic rickets (HR) is conventionally treated with phosphate and calcitriol. Exploring genotype and phenotypic spectrum of X-linked hypophosphatemic rickets (XLHR), focusing on short-term, long-term, and pubertal impact of conventional treatment was aimed.
Methods
Sixteen patients from 12 unrelated families with HR were analyzed for phosphate regulating endopeptidase homolog X-linked (PHEX) mutation. Initially Sanger sequencing analysis was performed. If PHEX mutation was not detected, multiplex ligation-dependent probe amplification (MLPA) was performed. If molecular defect was detected, first-degree relatives were analyzed. Thirteen patients (81%) and five first-degree relatives with XLHR were evaluated for genotype–phenotype or gender-phenotype correlation. Clinical characteristics and response to conventional treatment were determined retrospectively.
Results
Nine different PHEX mutations were identified; four splice-site, three point mutations, and two single exon deletions. Four were novel mutations. Despite conventional treatment, median adult height was lower than median height on admission (−3.8 and −2.3 SDS, respectively), metabolic and radiographic recovery were not achieved, adherence was low (30%). Although mean adult height was better in compliant patients than noncompliants (−2.6 vs. −3.7 SDS, respectively), they were still short. Correlation between phenotype and genotype or gender could not be shown. Median phosphate decreased significantly throughout puberty (p=0.014). Median pubertal height was lower than prepubertal height (−4.4 vs. −3.6 SDS; respectively), pubertal growth spurt was not observed. Among five patients with a follow-up longer than five years, three had nephrocalcinosis (60%), two had hyperparathyroidism (40%), 4/6 (33%) required correction osteotomy.
Conclusions
Conventional treatment appears to have limited effect on metabolic, clinical and radiographic recovery in XLHR. Metabolic control and growth worsened during puberty. Although, long-term adverse effects are yet to be seen, introduction of burosumab as first-line treatment may be an alternative after infancy.
Funding source: Pediatrik Endokrin Araştırma Derneği (PENAR)
Acknowledgments
We thank the participating patients and families and all staff at Pediatric Endocrinology and Developmental Pediatrics
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Research funding: This study was supported by “Pediatrik Endokrin Araştırma Derneği (PENAR)”.
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Author contributions: M.A. performed genetic analysis, Y.U. collected and analyzed the data. Y.U. drafted the initial manuscript and A.O., N.G., N.K., M.A. and A.A. gave relevant expert input and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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Competing interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The study was approved by local Non-invasive Clinical Research Ethics Committee (2019/05-20).
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© 2021 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review Article
- Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents
- Original Articles
- Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review
- Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study
- Growth hormone replacement therapy: is it safe to use in children with asymptomatic pituitary lesions?
- Comparing adolescent self staging of pubertal development with hormone biomarkers
- Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia
- The concordance between ultrasonographic stage of breast and Tanner stage of breast for overweight and obese girls: a school population-based study
- Cross-sectional analysis: clinical presentation of children with persistently low ALP levels
- The utility of continuous glucose monitoring systems in the management of children with persistent hypoglycaemia
- Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation
- Role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children living with type 1 diabetes mellitus
- Investigation of quality of life in obese adolescents: the effect of psychiatric symptoms of obese adolescent and/or mother on quality of life
- Predictive value of WHO vs. IAP BMI charts for identification of metabolic risk in Indian children and adolescents
- Case Reports
- COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1
- Aromatase deficiency in an Ontario Old Order Mennonite family
- A case of monogenic diabetes mellitus caused by a novel heterozygous RFX6 nonsense mutation in a 14-year-old girl
Articles in the same Issue
- Frontmatter
- Review Article
- Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents
- Original Articles
- Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review
- Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study
- Growth hormone replacement therapy: is it safe to use in children with asymptomatic pituitary lesions?
- Comparing adolescent self staging of pubertal development with hormone biomarkers
- Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia
- The concordance between ultrasonographic stage of breast and Tanner stage of breast for overweight and obese girls: a school population-based study
- Cross-sectional analysis: clinical presentation of children with persistently low ALP levels
- The utility of continuous glucose monitoring systems in the management of children with persistent hypoglycaemia
- Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation
- Role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children living with type 1 diabetes mellitus
- Investigation of quality of life in obese adolescents: the effect of psychiatric symptoms of obese adolescent and/or mother on quality of life
- Predictive value of WHO vs. IAP BMI charts for identification of metabolic risk in Indian children and adolescents
- Case Reports
- COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1
- Aromatase deficiency in an Ontario Old Order Mennonite family
- A case of monogenic diabetes mellitus caused by a novel heterozygous RFX6 nonsense mutation in a 14-year-old girl
