When to suspect infantile hypercalcemia-1?

Area of Science:

• Endocrinology
• Genetics
• Biochemistry

Background:

• Infantile hypercalcemia-1 (HCINF1) diagnosis relies on mass spectroscopy (MS) measuring the 25(OH)D3/24,25(OH)2D3 ratio, with ratios > 80 prompting genetic analysis.
• The limited availability of MS and genetic testing leads to underdiagnosis of HCINF1.
• There is a need for accessible screening methods to identify potential HCINF1 cases.

Purpose of the Study:

• To establish serum calcium and parathyroid hormone (PTH) cut-off values for suspecting HCINF1.
• To evaluate the utility of these cut-offs in identifying HCINF1 patients, including adults.

Main Methods:

• Compared serum calcium and PTH levels in 6 HCINF1 patients with pathogenic CYP24A1 variants against three control groups (wild-type, age/sex-matched, vitamin D-matched).
• Validated identified cut-offs by assessing their ability to detect previously reported adult HCINF1 cases.
• Utilized mass spectroscopy (MS) for initial screening and genetic analysis for gold-standard diagnosis.

Main Results:

• Serum calcium > 9.6 mg/dL demonstrated 100% sensitivity and 91% specificity for distinguishing HCINF1 patients from wild-type subjects.
• A PTH index < 0.315 showed 100% sensitivity and 83.3% specificity.
• The calcium cut-off identified all adult HCINF1 cases, while the PTH cut-off identified 89.8%.

Conclusions:

• Serum calcium levels > 9.6 mg/dL and a PTH index < 0.315 are strong indicators for suspecting HCINF1.
• These biochemical markers can facilitate earlier identification of HCINF1 patients.
• Mass spectroscopy and genetic analysis remain crucial for definitive HCINF1 diagnosis.