One patient with perinatal hypophosphatasia due to mutations in the tissue-nonspecific alkaline phosphatase gene

Objective To explore the clinical and genetic characteristics of a Chinese baby with perinatal hypophosphatasia (HPP) and his parents for better understanding of the disease. Methods The clinical data of the patient with HPP was carefully collected. The laboratory and radiographic examination data were taken for this baby patient. Sequencing for all the twelve tissue-nonspecific alkaline phosphatase(ALPL) exons and the flanking exon-intron junctions were performed in the proband and his parents with their genomic DNA from peripheral blood. Results The blood level of alkaline phosphatase was decreased in this patient while serum calcium level was increased. His bone revealed chondrodysplasia-like change. Compound heterozygous mutations were found in the proband, with c. 346G>A(p.A116T) in exon 5 and c. 1171C>T(p.R391C) in exon 10. His father and mother were without clinical manifestation while respectively carried c. 346G>A(p.A116T and c. 1171C>T(p.R391C) missense mutations, suggesting an autosomal recessive inheritance in this family. Conclusion Perinatal HPP has a high mortality rate. Skeletal deformities, hypercalcemia, and low level of ALP are important in the differential diagnosis of perinatal HPP. Key words: Mutation; Hypophosphatasia; Alkaline phosphatase gene