Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Biochemical, clinical and genetic characteristics in adults with persistent hypophosphatasaemia; Data from an endocrinological outpatient clinic in Denmark

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopy Vegfa overexpression

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The role of the P2X7 receptor on bone loss in a mouse model of inflammation-mediated osteoporosis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. One year of Football Fitness improves L1-L4 BMD, postural balance and muscle strength in women treated for breast cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Bone phenotype of P2X4 receptor knockout mice: implication of a P2X7 receptor mutation?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummer101101
TidsskriftBone Reports
Vol/bind15
ISSN2352-1872
DOI
StatusUdgivet - dec. 2021

ID: 66726129