The diagnosis of hypophosphatasia in children as a multidisciplinary effort: an expert opinion.
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
26 Sep 2023
26 Sep 2023
Historique:
received:
28
07
2023
accepted:
12
09
2023
medline:
27
9
2023
pubmed:
27
9
2023
entrez:
26
9
2023
Statut:
aheadofprint
Résumé
Hypophosphatasia (HPP) is a rare genetic disorder in which pathogenic variants of the ALPL gene lead to a marked decrease of tissue non-specific alkaline phosphatase (TNSALP) activity. Although HPP is a systemic disorder, its clinical manifestations are more evident on bones, teeth, muscle and central nervous system. The clinical spectrum ranges from severe forms with extreme skeletal deformities, respiratory impairment, seizures, to very mild forms with onset in late adulthood and few clinical signs. The diagnosis can be suspected by measurement of TNSALP activity, but the insufficient awareness among health professionals and the lack of official guidelines are responsible for delayed diagnosis in children with HPP. The purpose of the current document is to provide an expert opinion directed at optimizing the diagnostic pathway of pediatric HPP. From April to December 2022, a multidisciplinary working group of 6 experts including two pediatric endocrinologists, a pediatric neurologist, a pediatric odontologist, a clinical geneticist, and a molecular biologist gathered in a series of periodic meetings to discuss the main issues related to the diagnosis of HPP in children and formalize an Expert Opinion statement. The experts agreed on a diagnostic trail that begins with the recognition of specific clinical signs, leading to biochemical analyses of TNSALP activity and vitamin B6 serum concentration. Very important are the neurological and dental manifestation of the disease that should be thoroughly investigated. The evaluation of TNSALP activity must consider sex and age variability and low activity must be persistent. Repeated blood measurements are thus necessary. The molecular analysis is then mandatory to confirm the diagnosis and for genetic counseling.
Identifiants
pubmed: 37752373
doi: 10.1007/s40618-023-02199-w
pii: 10.1007/s40618-023-02199-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s).
Références
Whyte MP (2017) Hypophosphatasia: An overview For 2017. Bone 102:15–25
pubmed: 28238808
doi: 10.1016/j.bone.2017.02.011
Riancho-Zarrabeitia L, García-Unzueta M, Tenorio JA, Gómez-Gerique JA, Ruiz Pérez VL, Heath KE, Lapunzina P, Riancho JA (2016) Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults. Eur J Intern Med 29:40–45
pubmed: 26783040
doi: 10.1016/j.ejim.2015.12.019
Whyte MP (2010) Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci 1192:190–200
pubmed: 20392236
doi: 10.1111/j.1749-6632.2010.05387.x
Addison WN, Azari F, Sørensen ES, Kaartinen MT, McKee MD (2007) Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, upregulating osteopontin, and inhibiting alkaline phosphatase activity. J Biol Chem 282:15872–15883
pubmed: 17383965
doi: 10.1074/jbc.M701116200
Millan JL, Whyte MP (2016) Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int 98:398–416
pubmed: 26590809
doi: 10.1007/s00223-015-0079-1
Aniadasi A, Bertoldi M, Contestabile R, Bettati S, Cellini B, Di Salvo ML, Borri-Voltattorni C, Bossa F, Mozzarelli A (2007) Pyridoxal 5’-phosphate enzymes as target for therapeutic agents. Curr Med Chem 14:1291–1324
doi: 10.2174/092986707780597899
Waymire KG, Mahuren JD, Jaje JM, Guilarte SR (1995) Mice lacking tissue non-specific die from seizures due to defective metabolism of vitamin B-6. Nat Genet 11:45–51
pubmed: 7550313
doi: 10.1038/ng0995-45
Narisawa S, Wennberg C, Millán JL (2000) Abnormal vitamin B6 metabolism in alkaline phosphatase knock-out mice causes multiple abnoralities, but not impaired mineralization. J Pathol 193:125–133
doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH722>3.0.CO;2-Y
Michigami T, Ohata Y, Fujiwara M, Mochizuki H, Adachi M, Kitaoka T, Kubota T, Sawai H, Namba N, Hasegawa K, Fujiwara I, Ozono K (2020) Clinical practice guidelines for hypophosphatasia. Clin Pediatr Endocrinol 29:9–24
pubmed: 32029969
pmcid: 6958520
doi: 10.1297/cpe.29.9
Mornet E, Taillandier A, Domingues C, Dufour A, Benaloun E, Lavaud N, Wallon F, Rousseau N, Charle C, Guberto M, Muti C, Simon-Bouy B (2021) Hypophosphatasia: a genetic-based nosology and new insight in genotype-phenotype correlation. Eur J Hum Genet 29:289–299
pubmed: 32973344
doi: 10.1038/s41431-020-00732-6
Mornet E, Yvard A, Taillandier A, Fauvert D, Simon-Bouy B (2011) A molecular-based estimation of the prevalence of hypophosphatasia in the European population. Ann Hum Genet 75:439–445
pubmed: 21488855
doi: 10.1111/j.1469-1809.2011.00642.x
Whyte MP, Zhang F, Wenkert D, McAlister WH, Mack KE, Benigno MC, Coburn SP, Wagy S, Griffin DM, Ericson KL, Mumm S (2015) Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients. Bone 75:229–239
pubmed: 25731960
doi: 10.1016/j.bone.2015.02.022
Hogler W, Langman C, Gomes da Silva H, Fang S, Linglart A, Ozono K, Petryk A, Rockman-Greenberg C, Seefried L, Kishnani PS (2019) Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskel Dis 20:80
doi: 10.1186/s12891-019-2420-8
Whyte MP, Leung E, Wilcox W, Liese J, Argente J, Martos-Moreno GA, Reeves A, Fujita KP, Moseley S, Hofmann C, Study 011-10 Investigators (2019) Natural history of perinatal and infantile hypophosphatasia: a retrospective study. J Pediatr 209:116–24.e4
pubmed: 30979546
doi: 10.1016/j.jpeds.2019.01.049
Whyte MP, Wenkert D, Zhang F (2016) Hypophosphatasia: Natural history study of 101 affected children investigated at one research center. Bone 93:125–138
pubmed: 27576207
doi: 10.1016/j.bone.2016.08.019
Millán JL, Narisawa S, Lemire I, Loisel TP, Boileau G, Leonarol P, Gramatikova S, Terkeltaub R, Pleshko Camacho N, McKee MD, Crine P, Whyte MP (2008) Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res 23:777–787
pubmed: 18086009
doi: 10.1359/jbmr.071213
Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millán JL, Skrinar AM, Crine P, Landy H (2012) Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med 366:904–913
pubmed: 22397652
doi: 10.1056/NEJMoa1106173
Whyte MP, Simmons JH, Moseley S, Fujita KP, Bishop N, Salman NJ, Taylor J, Phillips D, McGinn M, McAlister WH (2019) Asfotase alfa for infants and young children with hypophosphatasia: 7 year outcomes of a single-arm, open-label, phase 2 extension trial. Lancet Diabetes Endocrinol 7:93–105
pubmed: 30558909
doi: 10.1016/S2213-8587(18)30307-3
Kishnani PS, Rockman-Greenberg C, Rauch F, Bhatti NT, Moseley S, Denker AE, Watsky E, Whyte MP (2019) Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia. Bone 121:149–162
pubmed: 30576866
doi: 10.1016/j.bone.2018.12.011
Hofmann CE, Harmatz P, Vockley J, Högler W, Nakayama H, Bishop N, Martos-Moreno GÁ, Moseley S, Fujita KP, Liese J, Rockman-Greenberg C, ENB-010-10 Study Group (2019) Efficacy and safety of asfotase alfa in infants and young children with hypophosphatasia: a phase 2 open-label study. J Clin Endocrinol Metab 104:2735–2747
pubmed: 30811537
pmcid: 6530655
doi: 10.1210/jc.2018-02335
Stürznickel J, Schmidt FN, von Vopelius E, Delsmann MM, Schmidt C, Jandl NM, Oheim R, Barvencik F (2021) Bone healing and reactivation of remodeling under asfotase alfa therapy in adult patients with pediatric-onset hypophosphatasia. Bone 143:115794
pubmed: 33301963
doi: 10.1016/j.bone.2020.115794
Sugiyama Y, Watanabe T, Tajika M, Matsuhashi T, Shimura M, Fushimi T, Ichimoto K, Matsunaga A, Ebihara T, Tsuruoka T, Akiiyama T, Murayama K (2022) A Japanese single-center experience of the efficacy and safety of asfotase alfa in pediatric-onset hypophosphatasia. Orphanet J Rare Dis 17:78
pubmed: 35197081
pmcid: 8867653
doi: 10.1186/s13023-022-02230-y
Kim I, Noh E-S, Kim M-S, Jang J-H, Jeon TY, Choi HW, Cho SY (2023) Six-year clinical outcomes of enzyme replacement therapy for perinatal lethal and infantile hypophosphatasia in Korea: Two case reports. Medicine (Baltimore) 102:e32800d
doi: 10.1097/MD.0000000000032800
Braga F, Frusciante E, Infusino I, Aloisio E, Guerra E, Ceriotti F, Panteghini M (2017) Evaluation of the trueness of serum alkaline phosphatase measurement in a group of Italian laboratories. Clin Chem Lab Med 55:e47–e50
pubmed: 27718481
doi: 10.1515/cclm-2016-0605
Ridefelt P, Gustafsson J, Aldrimer M, Hellberg D (2014) Alkaline phosphatase in healthy children: reference intervals and prevalence of elevated levels. Horm Res Paediatr 82:399–404
pubmed: 25531333
doi: 10.1159/000369205
Adeli K, Higgins V, Seccombe D, Collier CP, Balion CM, Cembrowski G, Venner AA, Shaw J, CSCC reference interval harmonization (hRI) working group (2017) National survey of adult and pediatric reference intervals in clinical laboratories across Canada: a report of the CSCC working group on reference interval harmonization. Clin Biochem 50:925–935
pubmed: 28647526
doi: 10.1016/j.clinbiochem.2017.06.006
Wanjian G, Jie H, Liang G, Cheng W, Tian X, Jianjiang S, Chunni Z (2017) Establishment of reference interval for alkaline phosphatase in healthy children of various ethnicities, aged 0–12 years. Lab Med 48:166–171
pubmed: 28340217
doi: 10.1093/labmed/lmx017
Zierk J, Arzideh F, Haeckel R, Cario H, Frühwald MC, Groß HJ, Gscheidmeier T, Hoffmann R, Krebs A, Lichtinghagen R, Neumann M, Ruf HG, Steigerwald U, Streichert T, Rascher W, Metzler M, Rauh M (2017) Pediatric reference intervals for alkaline phosphatase. Clin Chem Lab Med 55:102–110
pubmed: 27505090
doi: 10.1515/cclm-2016-0318
Turan S, Topcu B, Gökçe İ, Güran T, Atay Z, Omar A, Akçay T, Bereket A (2011) Serum alkaline phosphatase levels in healthy children and evaluation of alkaline phosphatase z-scores in different types of rickets. J Clin Res Pediatr Endocrinol 3:7–11
pubmed: 21448327
pmcid: 3065317
doi: 10.4274/jcrpe.v3i1.02
Lü KL, Xie SS, Liu E, Yu XM, Wang L, Yang ZY, Xiong Q, Luo XG, Yang W, Liao W, Zhang YP (2020) Age-wise trends in alkaline phosphatase activity in 167,625 Chinese children aged 0–18 years. Clin Biochem 79:34–40
pubmed: 32142736
doi: 10.1016/j.clinbiochem.2020.03.001
Mora S, Cafarelli L, Erba P, Puzzovio M, Zamproni I, Giacomet V, Viganò A (2009) Differential effect of age, gender and puberty on bone formation rate assessed by measurement of bone-specific alkaline phosphatase in healthy Italian children and adolescents. J Bone Miner Metab 27:721–726
pubmed: 19455384
doi: 10.1007/s00774-009-0092-4
Schmidt T, Schmidt C, Amling M, Kramer J, Barvencik F (2021) Prevalence of low alkaline phosphatase activity in laboratory assessment: is hypophosphatasia an underdiagnosed disease? Orphanet J Rare Dis 16:452
pubmed: 34711245
pmcid: 8555173
doi: 10.1186/s13023-021-02084-w
Whyte MP, Zhang F, Wenkert D, Mack KE, Bijanki VN, Ericson KL, Coburn SP (2022) Hypophosphatasia: vitamin B6 status of affected children and adults. Bone 154:116204
pubmed: 34547524
doi: 10.1016/j.bone.2021.116204
Panton KK, Farup PG, Sagen E, Sirum UF, Asberg A (2013) Vitamin B6—sample stability and reference limits. Scand J Clin Lab Investig 73:476–479
doi: 10.3109/00365513.2013.803234
González-Gross M, Benser J, Breidenassel C, Albers U, Huybrechts I, Valtueña J, Spinneker A, Segoviano M, Widhalm K, Molnar D, Moreno LA, Stehle P, Pietrzik K, HELENA Study group (2012) Gender and age influence blood folate, vitamin B12, vitamin B6 and homocysteine levels in European adolescents: the Helena Study. Nutr Res Rev 32:817–826
doi: 10.1016/j.nutres.2012.09.016
Taketani T (2015) Neurological simptoms of hypophosphatasia. Subcell Biochem 76:309–322
pubmed: 26219717
doi: 10.1007/978-94-017-7197-9_14
Eastman JR, Bixler D (1980) Urinary phosphoetanolamine: normal values by age. Clin Chem 26:12
doi: 10.1093/clinchem/26.12.1757
Imbard A, Alberti C, Armoogum-Boizeau P, Ottolenghi C, Josserand E, Rigal O, Benoist JF (2012) Phosphoetanolamine normal range in pediatric urines for hypophosphatasia screening. Clin Chem Lab Med 50:2231–2233
pubmed: 23093084
doi: 10.1515/cclm-2012-0266
Sebastián-Serrano Á, Engel T, de Diego-García L, Olivos-Oré LA, Arribas-Blázquez M, Martínez-Frailes C, Pérez-Díaz C, Millán JL, Artalejo AR, Miras-Portugal MT, Henshall DC, Díaz-Hernández M (2016) Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation. Hum Mol Genet 25:4143–4156
pubmed: 27466191
pmcid: 5291194
doi: 10.1093/hmg/ddw248
Pierpont EI, Simmons JH, Spurlock KJ, Shanley R, Sarafoglou KM (2021) Impact of pediatric hypophosphatasia on behavioral health and quality of life. Orphanet J Rare Dis 16:80
pubmed: 33579333
pmcid: 7881480
doi: 10.1186/s13023-021-01722-7
Colazo JM, Hu JR, Dahir KM, Simmons JH (2019) Neurological symptoms in hypophosphatasia. Osteoporos Int 30:469–480
pubmed: 30215116
doi: 10.1007/s00198-018-4691-6
Okawa R, Nakano K, Matsumoto M, Kawabata K, Ooshima T (2012) Oral manifestations of patients with hypophosphatasia. Ped Dent J 22:155–162
doi: 10.1016/S0917-2394(12)70266-5
Beumer J III, Trowbridge HO, Silverman S Jr, Eisenberg E (1973) Childhood hypophosphatasia and the premature loss of teeth. A clinical and laboratory study of seven cases. Oral Surg Oral Med Oral Pathol 35:631–640
pubmed: 4512507
doi: 10.1016/0030-4220(73)90028-5
Feeney C, Stanford N, Lee S, Barry S (2018) Hypophosphatasia and the importance of the general dental practitioner—a case series and discussion of upcoming treatments. Br Dent J 224:937–943
pubmed: 29999027
doi: 10.1038/sj.bdj.2018.441
Baab DA, Page RC, Morton T (1985) Studies of a family manifesting premature exfoliation of deciduous teeth. J Periodontol 56:403–409
pubmed: 3860637
doi: 10.1902/jop.1985.56.7.403
Okawa R, Kadota T, Matayoshi S, Nakano K (2020) Dental manifestations leading to the diagnosis of hypophosphatasia in two children. J Dent Child (Chic) 87:179–183
pubmed: 33349304
Van den Bos T, Handoko G, Niehof A, Ryan L, Coburn SP, Whyte MP, Beertsen W (2005) Cementum and dentin in hypophosphatasia. J Dent Res 84:1021–1025
pubmed: 16246934
doi: 10.1177/154405910508401110
Okawa R, Miura J, Kokomoto K, Kubota T, Kitaoka T, Ozono K, Nakano K (2017) Early exfoliation of permanent tooth in patient with HPP. Ped Dent J 27:173–178
doi: 10.1016/j.pdj.2017.08.005
Bloch-Zupan A (2016) Hypophosphatasia: diagnosis and clinical signs—a dental surgeon perspective. Int J Paediatr Dent 26:426–438
pubmed: 27030892
doi: 10.1111/ipd.12232
Kramer K, Chavez MB, Tran AT, Farah F, Tan MH, Kolli TN, Dos Santos EJL, Wimer HF, Millán JL, Suva LJ, Gaddy D, Foster BL (2021) Dental defects in the primary dentition associated with hypophosphatasia from biallelic ALPL mutations. Bone 143:115732
pubmed: 33160095
doi: 10.1016/j.bone.2020.115732
Reibel A, Manière M-C, Clauss F, Droz D, Alembik Y, Mornet E, Bloch-Zupan A (2009) Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. Orphanet J Rare Dis 4:6
pubmed: 19232125
pmcid: 2654544
doi: 10.1186/1750-1172-4-6
Tournis S, Yavropoulou MP, Polyzos SA, Doulgeraki A (2021) Hypophosphatasia. J. Clin Med 10:5676
Sperelakis-Beedham B, Taillandier A, Domingues C, Guberto M, Colin E, Porquet-Bordes V, Rothenbuhler A, Salles JP, Wenkert D, Zankl A, Muti C, Bacrot S, Simon-Bouy B, Mornet E (2021) Utility of genetic testing for prenatal presentations of hypophosphatasia. Mol Genet Metab 132:198–203
pubmed: 33549410
doi: 10.1016/j.ymgme.2021.01.009
Huggins E, Ong R, Rockman-Greenberg C, Flueckinger LB, Dahir KM, Kishnani PS (2020) Multigenerational case examples of hypophasphatasia: challenges in genetic counseling and disease management. Mol Genet Metab Rep 25:100661
pubmed: 33101980
pmcid: 7578550
doi: 10.1016/j.ymgmr.2020.100661
Chodirker BN, Coburn SP, Seargeant LE, Whyte MP, Greenberg CR (1990) Increased plasma pyridoxal-5′-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia. J Inherit Metab Dis 13:891–896
pubmed: 2079838
doi: 10.1007/BF01800216
Simon-Bouy B, Taillandier A, Fauvert D, Brun-Heath I, Serre JL, Armengod CG, Bialer MG, Mathieu M, Cousin J, Chitayat D, Liebelt J, Feldman B, Gérard-Blanluet M, Körtge-Jung S, King C, Laivuori H, Le Merrer M, Mehta S, Jern C, Sharif S, Prieur F, Gillessen-Kaesbach G, Zankl A, Mornet E (2008) Hypophosphatasia: molecular testing of 19 prenatal cases and discussion about genetic counseling. Prenat Diagn 28:993–998
pubmed: 18925618
doi: 10.1002/pd.2088
Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 30:473–483
pubmed: 1593914
doi: 10.1097/00005650-199206000-00002
Michielsen HJ, De Vries J, Van Heck GL (2003) Psychometric qualities of a brief self-rated fatigue measure the fatigue assessment scale. J Psychosom Res 54:345–352
pubmed: 12670612
doi: 10.1016/S0022-3999(02)00392-6
Lovibond SH, Lovibond PF (1995) Manual for the depression anxiety stress scales, 2nd edn. Psychology Foundation, Sydney
Randolph C, Tierney MC, Mohr E, Chase TN (1998) The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol 20:310–319
pubmed: 9845158
doi: 10.1076/jcen.20.3.310.823
Hayes MHS, Patterson DG (1921) Experimental development of the graphic rating method. Psychol Bull 18:98–99