# Clinical features of low serum alkaline phosphatase levels in children: A retrospective study

## TL;DR

This study highlights the clinical features of low alkaline phosphatase levels in children and emphasizes the need for early diagnosis of conditions like hypophosphatasia.

## Contribution

The study identifies age-specific clinical features associated with low ALP levels in children, aiding in early diagnosis of HPP.

## Key findings

- Neonates with low ALP levels often have preterm birth or low birth weight and infections.
- School-age children with low ALP levels frequently have a history of corticosteroid use.
- Adolescents with low ALP levels often show signs of malnutrition or chronic diarrhea.

## Abstract

Serum alkaline phosphatase (ALP), a biomarker of bone and liver metabolism, is often elevated in children; however, the lower reference limit is rarely considered. Hypophosphatasia (HPP) is characterized by low ALP levels and impaired mineralization of bone and teeth. Although enzyme replacement therapy is available, mild forms are diagnosed late owing to subtle symptoms and ALP levels falling within the adult reference range. In Japan, ALP analysis methods were updated in 2020 and now require value conversion. Pediatricians unfamiliar with these standards may overlook low ALP levels. We investigated whether the disease distribution varies by age and identified key features critical for diagnosis.

We analyzed serum ALP levels of patients aged <18 years who visited three Nippon Medical School hospitals between January 2020 and December 2022. The inclusion criteria were ALP levels within the adult reference range but below age‐ and sex‐specific pediatric norms. Patient age, sex, and medical history were recorded.

Among 16,125 ALP measurements from 5513 individuals, 239 cases (132 males and 107 females) met the inclusion criteria. In neonates, preterm birth or low birth weight was common, and 55.6% of the infants had infections. School‐age children frequently present with a history of corticosteroid use, while adolescents often exhibit signs of malnutrition or chronic diarrhea. One patient had a prior HPP diagnosis, and two were newly diagnosed.

Our findings underscore the importance of recognizing low ALP levels in pediatric patients and maintaining a high index of suspicion for HPP and other treatable conditions.