Rationale: Hypophosphatasia (HPP) is a very rare metabolic bone disease caused by loss-of-function mutations in the ALPL gene encoding the tissue nonspecific alkaline phosphatase. The severe neonatal form is considered lethal but insights into manifestations of the disease can help to increase our knowledge of the natural history for an early initiation of treatment and improvement of survival.
Patient concerns: We report the case of a newborn in which his fetal imaging showed findings of skeletal dysplasia disorder, considering initially achondroplasia as a potential diagnosis.
Diagnosis: A definitive diagnosis compatible with perinatal lethal HPP was established in the 1st days due to the presentation at birth with thoracic and pulmonary hypoplasia, bone hypomineralization, and undetectable alkaline phosphatase. The genetic analysis identified a new heterozygous c.413G>C mutation and another 1 c.473-2G>C previously described in the ALPL gene.
Outcomes: The patient died on the 4th day by clinical course complicated without having started enzyme replacement therapy (ERT). Retrospectively, previous analyzes of the parents already showed both a decreased alkaline phosphatase.
Lessons: This report highlights the importance of prenatal differential diagnosis of bone dysplasia with the key biochemical marker of alkaline phosphatase in the parents. Substitutive ERT administered very soon after birth, seems to change the prognosis in these patients with neonatal HPP.