Prospective phenotyping of long-term survivors of generalized arterial calcification of infancy (GACI).
ABCC6 deficiency
ENPP1 deficiency
autosomal recessive hypophosphatemic rickets type 2
generalized arterial calcification of infancy
pseudoxanthoma elasticum
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
06
07
2020
accepted:
18
09
2020
revised:
15
09
2020
pubmed:
3
10
2020
medline:
4
6
2021
entrez:
2
10
2020
Statut:
ppublish
Résumé
Generalized arterial calcification of infancy (GACI), characterized by vascular calcifications that are often fatal shortly after birth, is usually caused by deficiency of ENPP1. A small fraction of GACI cases result from deficiency of ABCC6, a membrane transporter. The natural history of GACI survivors has not been established in a prospective fashion. We performed deep phenotyping of 20 GACI survivors. Sixteen of 20 subjects presented with arterial calcifications, but only 5 had residual involvement at the time of evaluation. Individuals with ENPP1 deficiency either had hypophosphatemic rickets or were predicted to develop it by 14 years of age; 14/16 had elevated intact FGF23 levels (iFGF23). Blood phosphate levels correlated inversely with iFGF23. For ENPP1-deficient individuals, the lifetime risk of cervical spine fusion was 25%, that of hearing loss was 75%, and the main morbidity in adults was related to enthesis calcification. Four ENPP1-deficient individuals manifested classic skin or retinal findings of PXE. We estimated the minimal incidence of ENPP1 deficiency at ~1 in 200,000 pregnancies. GACI appears to be more common than previously thought, with an expanding spectrum of overlapping phenotypes. The relationships among decreased ENPP1, increased iFGF23, and rickets could inform future therapies.
Identifiants
pubmed: 33005041
doi: 10.1038/s41436-020-00983-0
pii: S1098-3600(21)02543-0
pmc: PMC7867608
mid: NIHMS1634645
doi:
Substances chimiques
FGF23 protein, human
0
Fibroblast Growth Factor-23
7Q7P4S7RRE
Phosphoric Diester Hydrolases
EC 3.1.4.-
Pyrophosphatases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
396-407Subventions
Organisme : Intramural NIH HHS
ID : Z99 HG999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HG200407
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
Rutsch F, Böyer P, Nitschke Y, et al. Hypophosphatemia, hyperphosphaturia, and bisphosphonate treatment are associated with survival beyond infancy in generalized arterial calcification of infancy. Circ Cardiovasc Genet. 2008;1:133–140.
doi: 10.1161/CIRCGENETICS.108.797704
Chong CR, Hutchins GM. Idiopathic infantile arterial calcification: the spectrum of clinical presentations. Pediatr Dev Pathol. 2008;11:405–415.
doi: 10.2350/07-06-0297.1
Nitschke Y, Baujat G, Botschen U, et al. generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. Am J Hum Genet. 2012;90:25–39.
doi: 10.1016/j.ajhg.2011.11.020
Jansen RS, Küçükosmanoglu A, de Haas M, et al. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013;110:20206–20211.
doi: 10.1073/pnas.1319582110
Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc Natl Acad Sci U S A. 2000;97:6001–6006.
doi: 10.1073/pnas.100041297
Jansen RS, Duijst S, Mahakena S, et al. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014;34:1985–1989.
doi: 10.1161/ATVBAHA.114.304017
Lorenz-Depiereux B, Schnabel D, Tiosano D, Häusler G, Strom TM. Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet. 2010;86:267–272.
doi: 10.1016/j.ajhg.2010.01.006
Levy-Litan V, Hershkovitz E, Avizov L, et al. Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. Am J Hum Genet. 2010;86:273–278.
doi: 10.1016/j.ajhg.2010.01.010
Brachet C, Mansbach AL, Clerckx A, Deltenre P, Heinrichs C. Hearing loss is part of the clinical picture of ENPP1 loss of function mutation. Horm Res Paediatr. 2014;81:63–66.
doi: 10.1159/000354661
Le Boulanger G, Labrèze C, Croué A, et al. An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. Am J Med Genet A. 2010;152A:118–123.
doi: 10.1002/ajmg.a.33162
Gopalakrishnan S, Shah S, Apuya JS, Martin T. Anesthetic management of a patient with idiopathic arterial calcification of infancy and fused cervical spine. Paediatr Anaesth. 2008;18:1006–1007.
doi: 10.1111/j.1460-9592.2008.02585.x
Lockitch G, Halstead AC, Albersheim S, MacCallum C, Quigley G. Age- and sex-specific pediatric reference intervals for biochemistry analytes as measured with the Ektachem-700 analyzer. Clin Chem. 1988;34:1622–1625.
doi: 10.1093/clinchem/34.8.1622
Lek M, Karczewski KJ, Minikel EV, et al. Analysis of protein-coding genetic variation in 60,706 humans. Nature. 2016;536:285–291.
doi: 10.1038/nature19057
Chourabi M, Liew MS, Lim S, et al. ENPP1 mutation causes recessive Cole disease by altering melanogenesis. J Invest Dermatol. 2018;138:291–300.
doi: 10.1016/j.jid.2017.08.045
Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–249.
doi: 10.1038/nmeth0410-248
Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009;4:1073–1081.
doi: 10.1038/nprot.2009.86
Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46:310–315.
doi: 10.1038/ng.2892
Estey MP, Cohen AH, Colantonio DA, et al. CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort. Clin Biochem. 2013;46:1197–1219.
doi: 10.1016/j.clinbiochem.2013.04.001
Stark H, Eisenstein B, Tieder M, Rachmel A, Alpert G. Direct measurement of TP/GFR: a simple and reliable parameter of renal phosphate handling. Nephron. 1986;44:125–128.
doi: 10.1159/000184216
Legrand A, Cornez L, Samkari W, et al. Mutation spectrum in the ABCC6 gene and genotype–phenotype correlations in a French cohort with pseudoxanthoma elasticum. Genet Med. 2017;19:909–917.
doi: 10.1038/gim.2016.213
Erben RG. Physiological actions of fibroblast growth factor-23. Front Endocrinol (Lausanne). 2018;9:267.
doi: 10.3389/fendo.2018.00267
Bashiri A, Borick JL. Recurrent pregnancy loss: definitions, epidemiology, and prognosis. In: Bashiri A, Harlev A, Agarwal A, editors. Recurrent pregnancy loss: evidence-based evaluation, diagnosis and treatment. Heidelberg: Springer; 2016. p. 3–18.
Høst A, Halken S. A prospective study of cow milk allergy in Danish infants during the first 3 years of life. Clinical course in relation to clinical and immunological type of hypersensitivity reaction. Allergy. 1990;45:587–596.
doi: 10.1111/j.1398-9995.1990.tb00944.x
Kotwal A, Ferrer A, Kumar R, et al. Clinical and biochemical phenotypes in a family with ENPP1 mutations. J Bone Miner Res. 2020;35:662–670.
doi: 10.1002/jbmr.3938
Chen J, Song D, Wang X, Shen X, Li Y, Yuan W. Is ossification of posterior longitudinal ligament an enthesopathy? Int Orthop. 2011;35:1511–1516.
doi: 10.1007/s00264-010-1163-9
Polisson RP, Martinez S, Khoury M, et al. Calcification of entheses associated with X-linked hypophosphatemic osteomalacia. N Engl J Med. 1985;313:1–6.
doi: 10.1056/NEJM198507043130101
Che H, Roux C, Etcheto A, et al. Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol. 2016;174:325–333.
doi: 10.1530/EJE-15-0661
Karaplis AC, Bai X, Falet J-P, Macica CM. Mineralizing enthesopathy is a common feature of renal phosphate-wasting disorders attributed to FGF23 and is exacerbated by standard therapy in hyp mice. Endocrinology. 2012;153:5906–5917.
doi: 10.1210/en.2012-1551
Chen A, Ro H, Mundra VRR, et al. Description of 5 novel SLC34A3/NPT2c mutations causing hereditary hypophosphatemic rickets with hypercalciuria. Kidney Int Rep. 2019;4:1179–1186.
doi: 10.1016/j.ekir.2019.05.004
Zhang J, Dyment NA, Rowe DW, et al. Ectopic mineralization of cartilage and collagen-rich tendons and ligaments in Enpp1asj-2J mice. Oncotarget. 2016;7:12000–12009.
doi: 10.18632/oncotarget.7455
Tian C, Harris BS, Johnson KR. Ectopic mineralization and conductive hearing loss in Enpp1asj mutant mice, a new model for otitis media and tympanosclerosis. PLoS One. 2016;11:e0168159.
doi: 10.1371/journal.pone.0168159
Whyte MP, Landt M, Ryan LM, et al. Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5’-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. J Clin Invest. 1995;95:1440–1445.
doi: 10.1172/JCI117814
Bistarakis L, Voskaki I, Lambadaridis J, Sereti H, Sbyrakis S. Renal handling of phosphate in the first six months of life. Arch Dis Child. 1986;61:677–681.
doi: 10.1136/adc.61.7.677
Stöhr R, Schuh A, Heine GH, Brandenburg V. FGF23 in cardiovascular disease: innocent bystander or active mediator? Front Endocrinol (Lausanne). 2018;9:351.
doi: 10.3389/fendo.2018.00351
Connor J, Olear EA, Insogna KL, et al. Conventional therapy in adults with X-linked hypophosphatemia: effects on enthesopathy and dental disease. J Clin Endocrinol Metab. 2015;100:3625–3632.
doi: 10.1210/JC.2015-2199
Schmitt CP, Mehls O. The enigma of hyperparathyroidism in hypophosphatemic rickets. Pediatr Nephrol. 2004;19:473–477.
doi: 10.1007/s00467-004-1443-y
Verge CF, Lam A, Simpson JM, Cowell CT, Howard NJ, Silink M. Effects of therapy in X-linked hypophosphatemic rickets. N Engl J Med. 1991;325:1843–1848.
doi: 10.1056/NEJM199112263252604
Ferreira CR, Ziegler SG, Gupta A, Groden C, Hsu KS, Gahl WA. Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification. Am J Med Genet A. 2016;170A:1308–1311.
doi: 10.1002/ajmg.a.37574
Ziegler SG, Ferreira CR, MacFarlane EG, et al. Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase. Sci Transl Med. 2017;9:eaal1669.
doi: 10.1126/scitranslmed.aal1669
Nitschke Y, Yan Y, Buers I, Kintziger K, Askew K, Rutsch F. ENPP1-Fc prevents neointima formation in generalized arterial calcification of infancy through the generation of AMP. Exp Mol Med. 2018;50:139.
doi: 10.1038/s12276-018-0163-5