Top

Journal of Endocrinological Investigation

Published in:

01-07-2022 | Hypophosphatemic Rickets | Original Article

Growth in height and body proportion from birth to adulthood in hereditary hypophosphatemic rickets: a retrospective cohort study

Authors: M. del Pino, G. L. Viterbo, M. A. Arenas, N. Perez Garrido, P. Ramirez, R. Marino, A. Belgorosky, V. Fano

Published in: Journal of Endocrinological Investigation | Issue 7/2022

Abstract

Purpose

Patients with hereditary hypophosphatemic rickets are short and disproportionate and very little information is available on segmental growth, but the body disproportion at adulthood leads us to think that the growth velocity of legs is slower.

Methods

A total of 96 children were included and molecular testing was carried out in 42. Children who reached adult height were classified into two groups according to their compliance to conventional treatment (phosphate supplement and calcitriol). Individual growth records of height and sitting height/height were plotted using Argentine reference data in 96 children and growth curves were estimated by fitting Preece-Baines Model 1 in 19 of the children.

Results

Molecular testing revealed sequence deleterious alterations or large deletions in 36/42 patients. During childhood, 76% of children grew below − 1.88 standard deviation score (SDS) and 97% had body disproportion. During adolescence, the mean peak height velocity for the good and poor compliance to treatment groups was 7.8 (0.6) and 5.4 (0.4) cm/year in boys and 7.0 (0.7) and 5.2 (0.8) cm/year in girls, respectively. At adulthood, the median sitting height/height ratio was 2.32 and 6.21 SDS for the good and poor compliance to treatment groups, respectively. The mean pubertal growth spurt of the trunk was –0.8 (1.4) SDS, with a short pubertal growth spurt of − 1.8 (0.4) SDS for limbs in the good compliance group. Median adult height in 13/29 males and 30/67 females was –4.56 and –3.16 SDS, respectively.

Conclusion

For all patients the growth spurt was slower, secondary to a short growth spurt of limbs, reaching a short adult height with body disproportion that was more prominent in the poor compliance group.

Capelli S, Donghi V, Maruca K, Vezzoli G, Corbetta S, Brandi ML, Mora S, Weber G (2015) Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets. Bone 79(143–149):12. https://doi.org/10.1016/j.bone.2015.05.040CrossRef

Razali NN, Hwu TT, Thilakavathy K (2015) Phosphate homeostasis and genetic mutations of familial hypophosphatemic rickets. J Pediatr Endocrinol Metab JPEM 28(9–10):1009–1017. https://doi.org/10.1515/jpem-2014-0366CrossRefPubMed

Bastepe M, Jüppner H (2008) Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord 9(2):171–180. https://doi.org/10.1007/s11154-008-9075-3CrossRefPubMed

Glorieux FH, Pettifor JM, Jüppner H (2012) Pediatric Bone. Biology and diseases. Academic Press, USA

Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL (2011) A clinician’s guide to X-linked hypophosphatemia. J Bone Min Res Off J Am Soc Bone Min Res 26(7):1381–1388. https://doi.org/10.1002/jbmr.340CrossRef

Linglart A, Biosse-Duplan M, Briot K, Chaussain C, Esterle L, Guillaume-Czitrom S, Kamenicky P, Nevoux J, Prié D, Rothenbuhler A, Wicart P, Harvengt P (2014) Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect 3(1):R13–R30. https://doi.org/10.1530/EC-13-0103CrossRefPubMedPubMedCentral

Imel EA, Carpenter TO (2015) A practical clinical approach to paediatric phosphate disorders. Endocr Dev 28:134–161. https://doi.org/10.1159/000381036CrossRefPubMed

Rafaelsen S, Johansson S, Ræder H, Bjerknes R (2016) Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. Eur J Endocrinol 174(2):125–136. https://doi.org/10.1530/EJE-15-0515CrossRefPubMed

Courbebaisse M, Lanske B (2018) Biology of fibroblast growth factor 23: from physiology to pathology. Cold Spring Harb Perspect Med 8(5):a031260. https://doi.org/10.1101/cshperspect.a031260CrossRefPubMedPubMedCentral

10.

- Arenas, Maria; Jaimovich, Sebastian; Perez Garrido, Natalia; del Pino, Mariana; Viterbo, Gisela; Marino, Roxana;and Fano, Virginia; Hereditary Hypophosphatemic Rickets and Craniosynostosis https://doi.org/10.1515/jpem-2021-0042

11.

Carpenter TO, Whyte MP, Imel EA, Boot AM, Högler W, Linglart A, Padidela R, Van’t Hoff W, Mao M, Chen CY, Skrinar A, Kakkis E, San Martin J, Portale AA (2018) Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med 378(21):1987–1998. https://doi.org/10.1056/NEJMoa1714641CrossRefPubMed

12.

Imel EA, Glorieux FH, Whyte MP et al (2019) Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet (London, England) 393(10189):2416–2427. https://doi.org/10.1016/S0140-6736(19)30654-3CrossRef

13.

Mao M, Carpenter TO, Whyte MP, Skrinar A, Chen CY, San Martin J, Rogol AD (2020) Growth curves for children with X-linked hypophosphatemia. J Clin Endocrinol Metab 105(10):495. https://doi.org/10.1210/clinem/dgaa495CrossRef

14.

Fano V, del Pino M, Caletti MG, Delgado A, Turconi A, Mendilaharzu H, Lejarraga H (2008) Crecimiento a largo plazo de pacientes con raquitismo hipofosfatémico familiar (RHF). Med Infantil XV:243–247

15.

Santos F, Fuente R, Mejia N, Mantecon L, Gil-Peña H, Ordoñez FA (2013) Hypophosphatemia and growth. Pediatr Nephrol (Berl, Germany) 28(4):595–603. https://doi.org/10.1007/s00467-012-2364-9CrossRef

16.

Zivičnjak M, Schnabel D, Billing H, Staude H, Filler G, Querfeld U, Schumacher M, Pyper A, Schröder C, Brämswig J, Haffner D (2011) Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets. Pediatr Nephrol (Berl, Germany) 26(2):223–231. https://doi.org/10.1007/s00467-010-1705-9CrossRef

17.

Beck-Nielsen SS, Brusgaard K, Rasmussen LM, Brixen K, Brock-Jacobsen B, Poulsen MR, Vestergaard P, Ralston SH, Albagha OM, Poulsen S, Haubek D, Gjørup H, Hintze H, Andersen MG, Heickendorff L, Hjelmborg J, Gram J (2010) Phenotype presentation of hypophosphatemic rickets in adults. Calcif Tissue Int 87(2):108–119. https://doi.org/10.1007/s00223-010-9373-0CrossRefPubMed

18.

Steendijk R, Herweijer TJ (1984) Height, sitting height and leg length in patients with hypophosphataemic rickets. Acta Paediatr Scand 73(2):181–184. https://doi.org/10.1111/j.1651-2227.1984.tb09925.xCrossRefPubMed

19.

Steendijk R, Hauspie RC (1992) The pattern of growth and growth retardation of patients with hypophosphataemic vitamin D-resistant rickets: a longitudinal study. Eur J Pediatr 151(6):422–427. https://doi.org/10.1007/BF01959355CrossRefPubMed

20.

Mäkitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E (2003) Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 88(8):3591–3597. https://doi.org/10.1210/jc.2003-030036CrossRefPubMed

21.

Morey M, Castro-Feijóo L, Barreiro J, Cabanas P, Pombo M, Gil M, Bernabeu I, Díaz-Grande JM, Rey-Cordo L, Ariceta G, Rica I, Nieto J, Vilalta R, Martorell L, Vila-Cots J, Aleixandre F, Fontalba A, Soriano-Guillén L, García- Sagredo JM, García-Miñaur S, Loidi L (2011) Genetic diagnosis of X-linked dominant Hypophosphatemic Rickets in a cohort study: tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type. BMC Med Genet 12:116. https://doi.org/10.1186/1471-2350-12-116CrossRefPubMedPubMedCentral

22.

Holm IA, Nelson AE, Robinson BG, Mason RS, Marsh DJ, Cowell CT, Carpenter TO (2001) Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 86(8):3889–3899. https://doi.org/10.1210/jcem.86.8.7761CrossRefPubMed

23.

del Pino M, Viterbo GL, Fano V (2017) GAP2017 Manejo de Niños con Raquitismo Hipofosfatémico Familiar. http://garrahan.gov.ar/images/intranet/guias_atencion/GAP_2017_-_MANEJO_RAQUITISMO.pdf. Accessed 26 Dec 2020

24.

Lejarraga H, Heinrich JJ, Rodríguez A (1975) Normas y técnicas de mediciones antropométricas. Rev del Hosp de Niños 17:165–171

25.

Caíno S, Adamo P, Kelmansky D, Lejarraga H (2002) Impacto del entrenamiento sobre el error de mediciones antropométricas. Arch Arg Ped 100:110–113

26.

Lejarraga H, del Pino M, Fano V, Caino S, Cole TJ (2009) Referencias de peso y estatura desde el nacimiento hasta la madurez para niñas y niños argentinos: Incorporación de datos de la OMS de 0 a 2 años, recálculo de percentilos para obtención de valores LMS [Growth references for weight and height for Argentinian girls and boys from birth to maturity: incorporation of data from the World Health Organization from birth to 2 years and calculation of new percentiles and LMS values]. Arch Argent de Pediatr 107(2):126–133. https://doi.org/10.1590/S0325-00752009000200006CrossRef

27.

del Pino M, Orden AB, Arenas MA, Fano V (2017) Argentine references for the assessment of body proportions from birth to 17 years of age Referencias argentinas para la evaluación de proporciones corporales desde el nacimiento hasta los 17 años. Arch Argent de Pediatr 115(3):234–240. https://doi.org/10.5546/aap.2017.eng.234CrossRef

28.

Thacher TD, Fischer PR, Pettifor JM, Lawson JO, Manaster BJ, Reading JC (2000) Radiographic scoring method for the assessment of the severity of nutritional rickets. J Trop Pediatr 46(3):132–139. https://doi.org/10.1093/tropej/46.3.132CrossRefPubMed

29.

Preece MA, Baines MJ (1978) A new family of mathematical models describing the human growth curve. Ann Hum Biol 5(1):1–24. https://doi.org/10.1080/03014467800002601CrossRefPubMed

30.

Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45(239):13–23. https://doi.org/10.1136/adc.45.239.13CrossRefPubMedPubMedCentral

31.

Tanner JM (1973) Growth at adolescence. Blackwell Scientific Publications, Oxford

32.

Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235):291–303. https://doi.org/10.1136/adc.44.235.291CrossRefPubMedPubMedCentral

33.

Rowe PS, Oudet CL, Francis F, Sinding C, Pannetier S, Econs MJ, Strom TM, Meitinger T, Garabedian M, David A, Macher MA, Questiaux E, Popowska E, Pronicka E, Read AP, Mokrzycki A, Glorieux FH, Drezner MK, Hanauer A, Lehrach H, O’Riordan JL (1997) Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP). Hum Mol Genet 6(4):539–549. https://doi.org/10.1093/hmg/6.4.539CrossRefPubMed

34.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Laboratory Quality Assurance Committee ACMG (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med Off J Am Coll Med Genet 17(5):405–424. https://doi.org/10.1038/gim.2015.30CrossRef

35.

Hauspie RC, Cameron N, Molinari L (2004) Methods in human growth research. University Press, United KingdomCrossRef

36.

Lejarraga H, Cusminsky M, Castro EP (1976) Age of onset of puberty in urban Argentinian children. Ann Hum Biol 3(4):379–381. https://doi.org/10.1080/03014467600001601CrossRefPubMed

37.

Orden AB, Vericat A, Apezteguía MC (2011) Age at menarche in urban Argentinian girls: association with biological and socioeconomic factors. Nthropologischer Anzeiger Bericht uber die biologisch anthropologische Literatur 68(3):309–322. https://doi.org/10.1127/0003-5548/2011/0109CrossRef

38.

Tanner JM, Whitehouse RH, Marubini E, Resele LF (1976) The adolescent growth spurt of boys and girls of the Harpenden Growth Study. Ann Hum Biol 3(2):109–126. https://doi.org/10.1080/03014467600001231CrossRefPubMed

39.

del Pino M, Orden AB, Arenas MA, Caíno S, Fano V (2016) Referencias argentinas de estatura sentada y longitud de miembros inferiores de 0 a 18 años. Med Infant XXXIII(4):279–286

40.

Kinoshita Y, Saito T, Shimizu Y, Hori M, Taguchi M, Igarashi T, Fukumoto S, Fujita T (2012) Mutational analysis of patients with FGF23-related hypophosphatemic rickets. Eur J Endocrinol 167(2):165–172. https://doi.org/10.1530/EJE-12-0071CrossRefPubMed

Title: Growth in height and body proportion from birth to adulthood in hereditary hypophosphatemic rickets: a retrospective cohort study
Authors: M. del Pino
G. L. Viterbo
M. A. Arenas
N. Perez Garrido
P. Ramirez
R. Marino
A. Belgorosky
V. Fano
Publication date: 01-07-2022
Publisher: Springer International Publishing
Keyword: Hypophosphatemic Rickets
Published in: Journal of Endocrinological Investigation / Issue 7/2022
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-022-01768-9

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2022

Potential biomarkers in the fibrosis progression of nonalcoholic steatohepatitis (NASH)

DOCK4 regulates ghrelin production in gastric X/A-like cells

Teprotumumab for Graves’ orbitopathy and ototoxicity: moving problems from eyes to ears?

Chronic urticaria and thyroid autoimmunity: a meta-analysis of case–control studies

An unusual case report of polycystic ovary syndrome

Autofluorescence of parathyroid glands during endocrine surgery with minimally invasive technique

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials