Antenatal presentation and early postnatal treatment of infantile hypercalcemia type 2

Area of Science:

• Genetics
• Pediatrics
• Endocrinology

Background:

• Infantile hypercalcemia (IH) is a rare genetic disorder presenting in early infancy.
• It is characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis.
• IH types 1 and 2 are caused by biallelic variants in CYP24A1 and SLC34A1, respectively.

Observation:

• A newborn was diagnosed antenatally with IH type 2 (IH2) based on echogenic kidneys.
• Trio whole-exome sequencing initially identified a heterozygous pathogenic variant in SLC34A1.
• Re-analysis revealed a second pathogenic variant in trans, initially overlooked due to high allele frequency.

Findings:

• The diagnosis of IH2 was confirmed through comprehensive genetic analysis.
• Postnatal screening detected hypercalcemia at week 1, enabling prompt treatment.
• Treatment involved phosphate supplementation and avoidance of vitamin D.

Implications:

• Early diagnosis and intervention are crucial for managing infantile hypercalcemia.
• This case highlights the importance of re-evaluating exome data when clinical suspicion persists.
• Timely treatment normalized biochemical parameters and prevented severe complications, underscoring the efficacy of current management strategies.