Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study

Hepp, Nicola; Frederiksen, Anja Lisbeth; Dunø, Morten; Jørgensen, Niklas Rye; Jensen, Jens–Erik Beck

doi:10.1007/s00198-022-06536-2

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…In terms of bone frailty, vertebral fractures were numerically less frequent in patients with persistent hypophosphatasaemia without identified cause. In the study by Hepp et al , 30 none of the HPP patients had vertebral fractures. The study by Genest et al found a significant correlation between low ALP levels and high spine BMD in a cohort of HPP patients.…”

Section: Discussionmentioning

confidence: 87%

Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years

Larid,

Vix,

Preuss

et al. 2024

RMD Open

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IntroductionHypophosphatasia (HPP) is a rare genetic disease caused by loss-of-function mutations in the ALPL gene encoding the tissue non-specific alkaline phosphatase (ALP). Mild HPP is usually misdiagnosed in adult age. While an elevated serum ALP value draws more attention than a low value, low serum ALP should be better recognised and may lead to HPP detection.MethodsPatients were selected from the records of the biochemistry department of six University Hospitals in France. Patients were hospitalised in the departments of rheumatology and internal medicine between 2007 and 2017.Results56 321 hospitalised patients had at least 2 serum ALP dosages and 664 of these patients had at least 2 low serum ALP≤35 UI/L. Among these 664 patients, 482 (72.6%) had fluctuating low values (mean age 62.9 years; 60% of women) and 182 patients (27.4%) had persistent low values below 35 IU/L (mean age 53.4 years; 67% of women). Among patients with persistent hypophosphatasaemia treated with bisphosphonates, 70.8% never had ALP measurement before treatment and 20.8% were treated despite an abnormal decrease of ALP. Genetic testing was performed in 18 patients and was positive in 11. Genetic diagnosis of HPP was at least 6.0% in persistent hypophosphatasaemia and at least 15.9% in patients with at least three symptoms suggestive of HPP.ConclusionIn this 10-year retrospective study, 0.32% of adult patients hospitalised in the rheumatology and internal medicine departments had persistently low serum ALP, and among them, 6% had genetically proven HPP. Reported hypophosphatasaemia represented only 3.6% of hospitalised patients.

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Section: Discussionmentioning

confidence: 87%

Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years

Larid,

Vix,

Preuss

et al. 2024

RMD Open

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“…In the Danish cohort of 40 adult HPP patients, the serum levels of ALP, bone-specific alkaline phosphatase, and PLP were significantly decreased, but the levels of PTH, OC, and β-CTX were comparable to those in the age-matched control cohort [ 35 ]. The concentration of N-terminal pro-peptide of type 1 procollagen in HPP patients decreased significantly (44.2 ± 1.4 vs. 53.7 ± 1.4 µg/L, p = 0.006), indicating that bone turnover was inhibited; the phosphate level of patients in this cohort was higher than that in the control group, but it was still within the normal reference range (1.16 (1.04–1.29) vs. 1.01 (0.92–1.15) mmol/L, p = 0.002), and the calcium level between the groups was similar [ 35 ]. In our study, two patients (PT-4 and PT5) had mild hyperphosphatemia, indicating impaired bone mineralization.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Adults

Ren

Wang

et al. 2023

Genes

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Hypophosphatasia (HPP) is an inherited disease caused by ALPL mutation, resulting in decreased alkaline phosphatase (ALP) activity and damage to bone and tooth mineralization. The clinical symptoms of adult HPP are variable, making diagnosis challenging. This study aims to clarify the clinical and genetic characteristics of HPP in Chinese adults. There were 19 patients, including 1 with childhood-onset and 18 with adult-onset HPP. The median age was 62 (32–74) years and 16 female patients were involved. Common symptoms included musculoskeletal symptoms (12/19), dental problems (8/19), fractures (7/19), and fatigue (6/19). Nine patients (47.4%) were misdiagnosed with osteoporosis and six received anti-resorptive treatment. The average serum ALP level was 29.1 (14–53) U/L and 94.7% (18/19) of patients had ALP levels below 40 U/L. Genetic analysis found 14 ALPL mutations, including three novel mutations—c.511C>G (p.His171Ala), c.782C>A (p.Pro261Gln), and 1399A>G (p.Met467Val). The symptoms of two patients with compound heterozygous mutations were more severe than those with heterozygous mutations. Our study summarized the clinical characteristics of adult HPP patients in the Chinese population, expanded the spectrum of pathogenic mutations, and deepened clinicians’ understanding of this neglected disease.

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Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know

Busse,

Lee,

Nagamani

2024

Curr Osteoporos Rep

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Biochemical and clinical manifestations in adults with hypophosphatasia: a national cross-sectional study

Cited by 5 publications

References 40 publications

Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years

Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years

Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Adults

Genetic Evaluation for Monogenic Disorders of Low Bone Mass and Increased Bone Fragility: What Clinicians Need to Know

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