ESPE Abstracts (2019) 92 P2-32

Pediatric Patients with Heterozygous ALPL Mutation show a Broad Clinical Phenotype

Corinna Melanie Brichta1, Michael Wurm2, Andreas Krebs1, Ekkehart Lausch1, Natascha Van der Werf-Grohmann1, Karl Otfried Schwab1


1Faculty of Medicine, University of Freiburg, Department of Pediatrics and Adolescence Medicine, Freiburg, Germany. 2University Children´s Hospital Regensburg, Clinic St. Hedwig, Regensburg, Germany


Introduction: Hypophosphatasia (HPP) is a congenital disorder of the bone and mineral metabolism. It is based on mutations in the ALPL gene, which codes for tissue-unspecific alkaline phosphatase (TNSAP). Methods:

The casuistic of 3 children with heterozygous ALPL mutation are presented. The patients were identified by laboratory data screening for reduced AP activity at the Children's Hospital of the University Hospital Freiburg.

Case Reports: Patient 1: 11-year-old boy with family dwarfism. Dental problems on the father's side are known. The boy had no complaints at the time of the study. The activity of alkaline phosphatase was reduced (AP 126 IU/l [152-369]), pyridoxalphosphate (PLP) was clearly elevated (> 100 µg/l, note: intake of vitamin preparation with vitamin B6) and phosphoethanolamine (PEA) in the urine was borderline increased (14.4 µmol/l). The mutation analysis revealed a heterozygous mutation in the ALPL gene (c.145[T>G]; [T=]), which has a function-reducing effect on the protein.

Patient 2: 12-year-old boy without positive family history for HPP-specific symptoms and without symptoms at the time of the study. The activity of alkaline phosphatase was slightly decreased (AP 139 IU/l [159-405]), PLP was increased (62 µg/l) and PEA in urine was also increased (23.8 µmol/l). The mutation analysis revealed a heterozygous mutation in the ALPL gene (c.1204delC;[C=]), which had a diminishing effect.

Patient 3: 13-year-old girl with chronic pain syndrome. The family anamnesis is bland. The patient suffers from recurrent severe muscular-skeletal pain and abdominal pain. The activity of alkaline phosphatase was slightly decreased (AP 80 IU/L [104-385]), PLP was significantly increased (> 100 µg/l) and PEA in urine was marginally increased (14.4 µmol/l). The mutation analysis revealed a heterozygous mutation in the ALPL gene (c.147[G>A]; [G=]), which has a function-reducing effect on the protein.

Conclusion: Children with heterozygous ALPL mutation show suggestive laboratory findings with reduced alkaline phosphatase activity and increased concentrations of substrates PLP and PEA. The clinical phenotype is highly variable, from asymptomatic carrier status to clinical manifestations with small stature or chronic muscular-skeletal pain. The indication for enzyme replacement therapy should be decided individually.

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