Perinatal severe hypophosphatasia: a case report

Abstract

Abstract Objectives Hypophosphatasia is a rare, inherited metabolic disorder characterized by low serum alkaline phosphatase activity. It is caused by mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP) [1], [2], [3]. The degree of skeletal malformation varies, but the severe form carries a very poor prognosis. Case presentation This study reports a male neonate diagnosed with infantile hypophosphatasia (HPP). Genetic analysis showed two heterozygous missense variants at nucleotides c.977G>T (protein Gly326Val) and c.862+4A>G (IVS8+4A>G) (protein NA). The two mutations originated separately from the parents, consistent with autosomal recessive infantile HPP. The pathogenic variant was ALPL exon-9-heterozygous, and the other allele was ALPL IVS8-heterozygous, a variant of uncertain significance. Conclusions This case of infantile HPP was caused by two heterozygous mutations. One of those is a novel genetic mutation needed for further study. Genetic consultation is recommended for future offspring of affected parents.