Transient Hyperparathyroidism and Severe Intrauterine Osteopenia Linked to Novel Homozygous TRPV6 Deletion

Placental calcium (Ca²⁺) transport is essential for foetal bone mineralisation and development, as well as for Ca²⁺ homoeostasis. Rare mutations in transient receptor potential vanilloid (TRPV) 6 of the infant cause insufficient maternal-foetal Ca²⁺ transport through the placenta. Although there is a limited number of cases, phenotype analyses of these patients show skeletal deformities and hyperparathyroidism. In this study, we identified a case with a homozygous mutation in the TRPV6 channel that leads to the deletion of the Ca²⁺ pore.

The neonate was born with skeletal abnormalities, increased umbilical cord PTH levels (75 pmol/L) and normal total Ca²⁺ level (2.06 mmol/L). Skeletal abnormalities improved during the first months of life.

⁴⁵Ca²⁺ uptake assays demonstrated loss-of-function, and biotinylation assays demonstrated failure of the channel to reach the cell surface.

These findings indicate that the TRPV6-p.Arg492* mutation affects maternal-foetal Ca²⁺ transport and explains the observed phenotype.