Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark
Background: Hypophosphatasia (HPP) is an inborn disease caused by pathogenic variants in ALPL. Low levels of alkaline phosphatase (ALP) are a biochemical hallmark of the disease. Scarce knowledge about the prevalence of HPP in Scandinavia exists, and the variable clinical presentations make diagnost...
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Elsevier
2021-12-01
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| Series: | Bone Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352187221003570 |
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| author | Nicola Hepp Anja Lisbeth Frederiksen Morten Duno Jakob Præst Holm Niklas Rye Jørgensen Jens-Erik Beck Jensen |
| author_facet | Nicola Hepp Anja Lisbeth Frederiksen Morten Duno Jakob Præst Holm Niklas Rye Jørgensen Jens-Erik Beck Jensen |
| author_sort | Nicola Hepp |
| collection | DOAJ |
| description | Background: Hypophosphatasia (HPP) is an inborn disease caused by pathogenic variants in ALPL. Low levels of alkaline phosphatase (ALP) are a biochemical hallmark of the disease. Scarce knowledge about the prevalence of HPP in Scandinavia exists, and the variable clinical presentations make diagnostics challenging. The aim of this study was to investigate the prevalence of ALPL variants as well as the clinical and biochemical features among adults with endocrinological diagnoses and persistent hypophosphatasaemia. Methods: A biochemical database containing ALP measurements of 26,121 individuals was reviewed to identify adults above 18 years of age with persistently low levels of ALP beneath range (≤ 35 ± 2.7 U/L). ALPL genetic testing, biochemical evaluations and assessment of clinical features by a systematic questionnaire among included patients, were performed. Results: Among 24 participants, thirteen subjects (54.2%) revealed a disease-causing variant in ALPL and reported mild clinical features of HPP, of which musculoskeletal pain was the most frequently reported (n = 9). The variant c. 571G > A; p.(Glu191Lys) was identified in six subjects, and an unreported missense variant (c.1019A > C; p.(His340Pro)) as well as a deletion of exon 2 were detected by genetic screening. Biochemical analyses showed no significant differences in ALP (p = 0.059), the bone specific alkaline phosphatase (BALP) (p = 0.056) and pyridoxal-5′-phosphate (PLP) (p = 0.085) between patients with an ALPL variant and negative genetic screening. Patients with a variant in ALPL had significantly higher PLP levels than healthy controls (p = 0.002). We observed normal ALP activity in some patients classified as mild HPP, and slightly increased levels of PLP in two subjects with normal genetic screening and four healthy controls. Among 51 patients with persistent hypophosphatasaemia, fifteen subjects (29.4%) received antiresorptive treatment. Two patients with unrecognized HPP were treated with bisphosphonates and did not show complications due to the treatment. Conclusions: Pathogenic variants in ALPL are common among patients with endocrinological diagnoses and low ALP. Regarding diagnostics, genetic testing is necessary to identify mild HPP due to fluctuating biochemical findings. Antiresorptive treatment is a frequent reason for hypophosphatasaemia and effects of these agents in adults with a variant in ALPL and osteoporosis remain unclear and require further studies. |
| first_indexed | 2024-12-14T14:25:34Z |
| format | Article |
| id | doaj.art-4c3b9cdc0b7e4128b51268f4bf5e9186 |
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| issn | 2352-1872 |
| language | English |
| last_indexed | 2024-12-14T14:25:34Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Bone Reports |
| spelling | doaj.art-4c3b9cdc0b7e4128b51268f4bf5e91862022-12-21T22:57:57ZengElsevierBone Reports2352-18722021-12-0115101101Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in DenmarkNicola Hepp0Anja Lisbeth Frederiksen1Morten Duno2Jakob Præst Holm3Niklas Rye Jørgensen4Jens-Erik Beck Jensen5Dept. of Endocrinology, Hvidovre University Hospital Copenhagen, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Corresponding author.Dept. of Clinical Genetics, Aalborg University Hospital, Ladegaardsgade 5, 9000 Aalborg C, Denmark; Dept. of Clinical Research, Aalborg University, Fredrik Bajers Vej 7K, 9220 Aalborg Ø, DenmarkDept. of Clinical Genetics, University Hospital Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, DenmarkDepartment of Endocrinology, Copenhagen University Hospital Herlev, Borgmester Ib Juuls Vej 1, 2730 Herlev, DenmarkDept. of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 13, 2600 Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3 B, 2200 Copenhagen, DenmarkDept. of Endocrinology, Hvidovre University Hospital Copenhagen, Kettegaard Alle 30, 2650 Hvidovre, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3 B, 2200 Copenhagen, DenmarkBackground: Hypophosphatasia (HPP) is an inborn disease caused by pathogenic variants in ALPL. Low levels of alkaline phosphatase (ALP) are a biochemical hallmark of the disease. Scarce knowledge about the prevalence of HPP in Scandinavia exists, and the variable clinical presentations make diagnostics challenging. The aim of this study was to investigate the prevalence of ALPL variants as well as the clinical and biochemical features among adults with endocrinological diagnoses and persistent hypophosphatasaemia. Methods: A biochemical database containing ALP measurements of 26,121 individuals was reviewed to identify adults above 18 years of age with persistently low levels of ALP beneath range (≤ 35 ± 2.7 U/L). ALPL genetic testing, biochemical evaluations and assessment of clinical features by a systematic questionnaire among included patients, were performed. Results: Among 24 participants, thirteen subjects (54.2%) revealed a disease-causing variant in ALPL and reported mild clinical features of HPP, of which musculoskeletal pain was the most frequently reported (n = 9). The variant c. 571G > A; p.(Glu191Lys) was identified in six subjects, and an unreported missense variant (c.1019A > C; p.(His340Pro)) as well as a deletion of exon 2 were detected by genetic screening. Biochemical analyses showed no significant differences in ALP (p = 0.059), the bone specific alkaline phosphatase (BALP) (p = 0.056) and pyridoxal-5′-phosphate (PLP) (p = 0.085) between patients with an ALPL variant and negative genetic screening. Patients with a variant in ALPL had significantly higher PLP levels than healthy controls (p = 0.002). We observed normal ALP activity in some patients classified as mild HPP, and slightly increased levels of PLP in two subjects with normal genetic screening and four healthy controls. Among 51 patients with persistent hypophosphatasaemia, fifteen subjects (29.4%) received antiresorptive treatment. Two patients with unrecognized HPP were treated with bisphosphonates and did not show complications due to the treatment. Conclusions: Pathogenic variants in ALPL are common among patients with endocrinological diagnoses and low ALP. Regarding diagnostics, genetic testing is necessary to identify mild HPP due to fluctuating biochemical findings. Antiresorptive treatment is a frequent reason for hypophosphatasaemia and effects of these agents in adults with a variant in ALPL and osteoporosis remain unclear and require further studies.http://www.sciencedirect.com/science/article/pii/S2352187221003570Alkaline phosphataseALPLHypophosphatasiaOsteoporosisBisphosphonates |
| spellingShingle | Nicola Hepp Anja Lisbeth Frederiksen Morten Duno Jakob Præst Holm Niklas Rye Jørgensen Jens-Erik Beck Jensen Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark Bone Reports Alkaline phosphatase ALPL Hypophosphatasia Osteoporosis Bisphosphonates |
| title | Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark |
| title_full | Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark |
| title_fullStr | Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark |
| title_full_unstemmed | Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark |
| title_short | Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark |
| title_sort | biochemical clinical and genetic characteristics in adults with persistent hypophosphatasaemia data from an endocrinological outpatient clinic in denmark |
| topic | Alkaline phosphatase ALPL Hypophosphatasia Osteoporosis Bisphosphonates |
| url | http://www.sciencedirect.com/science/article/pii/S2352187221003570 |
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