Background: Hypophosphatasia (HPP) is a rare metabolic bone disease caused by loss-of-function mutations in the gene ALPL encoding the tissue nonspecific alkaline phosphatase. HPP is associated with significant morbidity and mortality in pediatric patients, with high rates as high as %100 in perinatal-onset HPP. Serum alkaline phosphatase (ALP) activity is markedly reduced, which leads to increased serum/urine phosphoethanolamine (PEA), pyridoxal-5phosphate (PLP). Asfotase alfa is the first-in-class, bone-targeted, enzyme-replacement therapy designed to reverse the skeletal mineralization defects in HPP.
Objective and hypotheses: We present here a male infant with perinatal lethal HPP.
Method: He was a full-term infant of a G6P1 mother who delivered by Cesarean section. After birth, he was promptly intubated and ventilated because of respiratory distress. Prenatally, bone deformities had been noticed. On physical examination his weight was 3020 g. His skull bones were not formed. Radiographs demonstrated thin ribs, poor ossification of the skull, and epiphysis of the long bones. Laboratory examinations revealed serum ALP was 0 U/l, serum phosphate was 7.3 mg/dl (range 2.54.5), serum calcium was 9.8 mg/dl. Parathyroid hormone and serum 25-hydroxy vitamin D levels were normal. Perinatal lethal HPP diagnosis was based on physical findings, laboratory investigations, and radiographic skeletal features. Urine PEA and plasma PLP levels were markedly elevated (1081 μmol/l (range 15341), 3942 μg/l (range 050) respectively).Asfotase alfa (Strensiq) therapy (2 mg/kg per day s.c three times per week) was started at 30 day of age.
Results: Serum calcium and phosphate levels were normal but ALP levels increased as high as 12,700 U/l during treatment. He died at the age of 65 days because of ventilator associated pneumonia.
Conclusion: Perinatal lethal hypophosphatasia is the most severe form of HPP. These severely affected babies often die at or soon after birth from respiratory insufficiency due to pulmonary hypoplasia, a consequence of poorly mineralized bones of the chest. Therefore early treatment is crucial for prognosis.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology