TRPV6 Gene Mutation in a Dizygous Twin With Transient Neonatal Hyperparathyroidism

Maternal-fetal transport of calcium (Ca²⁺) is important for bone mineralization in fetal development. Insufficient Ca²⁺ transport causes transient neonatal hyperparathyroidism (TNHP). Transient receptor potential cation channel, subfamily V, member 6 (TRPV6), has been found to play an important role in the active transport of Ca²⁺ through the placenta. Recently, TRPV6 gene was found to be the gene responsible for TNHP with severe skeletal undermineralization. To date, only seven cases of TNHP caused by TRPV6 recessive mutations have been reported. We present a case of TNHP caused by TRPV6 gene mutations. A female newborn was hospitalized because of respiratory distress. Marked undermineralization of the skeleton was observed in X-ray imaging. Laboratory examination revealed markedly high PTH and absence of hypercalcemia along with vitamin D deficiency. Her twin brother presented with almost no symptoms. Maternal laboratory findings indicated normocalcemia, but vitamin D deficiency with a high PTH level for the lactation period was observed. We initially diagnosed the patient as having secondary hyperparathyroidism because of maternal vitamin D deficiency. Nevertheless, the reasons underlying the discordant clinical manifestations between the twin siblings remained unclear. Our analysis of TRPV6 gene clarified that the patient had compound heterozygote mutations, which were reported previously (p.Ile223Thr and p.Gly428Arg). Pathologic mutations in TRPV6 gene were not detected in the other sibling. The clinical symptoms in the patient were transient: they resolved during infancy. TNHP caused by TRPV6 gene mutations is a unique disease in terms of its transient pathology in utero and relief after birth.