Cross-sectional analysis: clinical presentation of children with persistently low ALP levels

Objectives: Low activity of serum alkaline phosphatase (ALP) is a hallmark of hypophosphatasia (HPP), but low readings of ALP are not always recognized in clinical routine. Understanding the clinical presentations associ-ated with low ALP may contribute to a timelier diagnosis of HPP. Methods: Data from paediatric patients with low ALP, excluding patients in intensive care and with oncological/ haematological disorders, were analysed. Most recent ALP values, previous diagnoses, medication and relevant symptoms were extracted from patient records at nine specialised centres and analysed descriptively. A rela-tionship between body height and ALP values was scruti-nised by linear regression. Results: Of 370 children, 15 (4.1%) had a diagnosis of HPP. In the subgroup without a diagnosis of HPP, 241(67.9%) out of 355 patients had one or more medical conditions known to be associated with low serum ALP. Of those, hypothyroid-ism, malnutrition and steroid administration were most frequent. Characteristic symptoms, particularly, short stat-ure, muscle weakness and delay of motor development were more frequent and ALP values were lower in patients with documented HPP diagnosis compared to patients without diagnosis of HPP (Oz-scores: -2.52) (interquartile range [IQR] = 0.20) vs. -1.96 (IQR = 0.87). A weak positive linear relationship between z-scores of ALP and body height was identified (p