Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

Adult Alkaline Phosphatase / genetics Cross-Sectional Studies Humans Hypophosphatasia / diagnosis
ALPL Alkaline phosphatase Hypophosphatasaemia Hypophosphatasia Metabolic bone diseases

Journal

Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602

Informations de publication

Date de publication:
17 02 2020
Historique:
received: 31 08 2019
accepted: 24 01 2020
entrez: 19 2 2020
pubmed: 19 2 2020
medline: 22 6 2021
Statut: epublish

Résumé

Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

Sections du résumé

BACKGROUND
Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants.
RESULTS
Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively.
CONCLUSIONS
In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

Identifiants

DOI: 10.1186/s13023-020-1315-y PMID: 32066479 PMC: PMC7026995
pubmed: 32066479
doi: 10.1186/s13023-020-1315-y
pii: 10.1186/s13023-020-1315-y
pmc: PMC7026995
doi:

Substances chimiques

ALPL protein, human EC 3.1.3.1
Alkaline Phosphatase EC 3.1.3.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

51

Références

Am J Med Genet A. 2017 Mar;173(3):601-610
pubmed: 28127875
Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9924-8
pubmed: 1409720
Eur J Hum Genet. 1998 Jul-Aug;6(4):308-14
pubmed: 9781036
Mol Genet Metab. 2002 Feb;75(2):143-53
pubmed: 11855933
J Clin Endocrinol Metab. 1996 Dec;81(12):4458-61
pubmed: 8954059
Hum Mutat. 2000 Mar;15(3):293
pubmed: 10679946
Osteoporos Int. 2017 Aug;28(8):2343-2348
pubmed: 28401263
Ann N Y Acad Sci. 2010 Mar;1192:190-200
pubmed: 20392236
Calcif Tissue Int. 2016 Apr;98(4):398-416
pubmed: 26590809
Eur J Hum Genet. 2014 Oct;22(10):1160-4
pubmed: 24569605
Eur J Intern Med. 2016 Apr;29:40-5
pubmed: 26783040
Mol Genet Metab. 2015 Nov;116(3):215-20
pubmed: 26432670
Hum Mutat. 2003 Jul;22(1):105-6
pubmed: 12815606
Hum Mol Genet. 1994 Sep;3(9):1683-4
pubmed: 7833929
Hum Mutat. 2001;18(1):83-4
pubmed: 11438998
Osteoporos Int. 2017 Sep;28(9):2653-2662
pubmed: 28547134
J Bone Miner Res. 2014 Apr;29(4):929-34
pubmed: 24123110
J Bone Miner Res. 2012 May;27(5):987-94
pubmed: 22322541
BMC Musculoskelet Disord. 2019 Feb 14;20(1):80
pubmed: 30764793
Nat Rev Endocrinol. 2016 Apr;12(4):233-46
pubmed: 26893260
J Bone Miner Res. 2014 Jul;29(7):1651-60
pubmed: 24443354
J Bone Miner Res. 2017 Oct;32(10):1977-1980
pubmed: 28731215
J Biol Chem. 2014 Aug 29;289(35):24168-79
pubmed: 25023282
J Bone Miner Res. 2015 Sep;30(9):1726-37
pubmed: 25736332
Metabolism. 2016 Oct;65(10):1522-30
pubmed: 27621187
Hum Mutat. 1999;13(2):171-2
pubmed: 10094560
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Bone Rep. 2016 Aug 26;5:228-232
pubmed: 28580391
Bone. 2015 Jun;75:229-39
pubmed: 25731960
Osteoporos Int. 2016 Mar;27(3):1251-1254
pubmed: 26446772
Ann Hum Genet. 2011 May;75(3):439-45
pubmed: 21488855
Bone. 2013 May;54(1):21-7
pubmed: 23352924
Bone. 2017 Sep;102:15-25
pubmed: 28238808
Genomics. 1997 Jun 1;42(2):364-6
pubmed: 9192863

Auteurs

C Tornero (C)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain. carolina.tornero@salud.madrid.org.

V Navarro-Compán (V)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain.

J A Tenorio (JA)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), ISCIII, Madrid, Spain.

S García-Carazo (S)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain.

A Buño (A)

Department of Clinical Biochemistry, La Paz University Hospital, Madrid, Spain.

I Monjo (I)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain.

C Plasencia-Rodriguez (C)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain.

J M Iturzaeta (JM)

Department of Clinical Biochemistry, La Paz University Hospital, Madrid, Spain.

P Lapunzina (P)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), ISCIII, Madrid, Spain.

K E Heath (KE)

Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, IdiPAZ, Universidad Autónoma de Madrid, Madrid, Spain.
CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), ISCIII, Madrid, Spain.
Skeletal dysplasia multidisciplinary Unit (UMDE), La Paz University Hospital, Madrid, Spain.

A Balsa (A)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain.

P Aguado (P)

Department of Rheumatology, La Paz University Hospital, IdiPAZ, Paseo de la Castellana, 261, 28046, Madrid, Spain.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Can we identify individuals with an ALPL...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Phosphoric monoester hydrolases › Phosphatase alcaline › Can we identify individuals with an ALPL...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études transversales › Can we identify individuals with an ALPL...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Can we identify individuals with an ALPL...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Erreurs innées du métabolisme › Erreurs innées du métabolisme des métaux › Hypophosphatasie › Can we identify individuals with an ALPL...