Charakterisierung von Patient:innen mit niedriger alkalischer Phosphatase

Ausprägung der klinischen Problematik und Zahl der Betroffenen mit Hypophosphatasie in einem ambulanten Kollektiv

Characterization of patients presenting with low serum alkaline phosphatase

Assessment of the clinical spectrum and prevalence of hypophosphatasia in an outpatient cohort

by Leonhard Sebastian Hummel
Doctoral thesis
Date of Examination:2025-06-18
Date of issue:2025-06-04
Advisor:Prof. Dr. Heide Siggelkow
Referee:Prof. Dr Arndt Schilling
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-11304

 

 

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Abstract

English

Patients with hypophosphatasia have limited health and quality of life. It is currently controversial whether patients with a heterozygous mutation actually have any significant clinical symptoms. On the other hand, the mild form of hypophosphatasia can resemble the clinical picture of osteoporosis and as such could be incorrectly treated with bisphosphonates, which is contraindicated in hypophosphatasia. The main task was to characterize those affected with a low alkaline phosphatase (AP) at the MVZ Endokrinologikum Göttingen between 2006 and 2020. It was of interest how many of the patients identified in this way were subsequently diagnosed with hypophosphatasia. With the help of the groups gained in this way (low AP with or without genetic evidence of hypophosphatasia) an attempt can be made to identify differences between the groups in terms of complaint burden and clinical expression of the disease. We examined 49 patients regarding age, gender, laboratory parameters (blood and urine samples, with special analysis regarding AP), functional Tests, incidence/types of fractures (also with regard to osteoporosis according to the DVO guidelines relevant fractures), bone density and quality as well as 10-year fracture risk (FRAX). The division into three groups was based on the genetic examination: those with a genetically proven mutation (21 patients), those without a genetically proven one mutation (13 patients) and those without genetic testing (17 patients). The three groups were then compared in terms of similarities and differences. The mutation c.571G>A (p.Glu191Lys) was the most common at 33%. Differences according to group division was reflected in the following parameters: There was an increased volume of fractures with 57% in the diseased group. The AP as well as bone-specific AP was lower in the sick group, while PLP was increased in the sick and non-sick people (due to the study design). The patients could not be distinguished by bone density or bone structure nor by the type of fracture. The groups did not differ in the fracture risk calculation, although the highest fracture risk according to BMD or TBS was always in the genetically diseased group.
Keywords: hypophosphatasia; alkaline phosphatase; osteoporosis
Schlagwörter: Hypophosphatasie; Alkalische Phosphatase; Osteoporose