Phosphate matters when investigating hypercalcemia: a mutation in SLC34A3 causing HHRH

Area of Science:

• Endocrinology
• Genetics
• Nephrology

Background:

• Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder.
• It stems from mutations in the SLC34A3 gene, affecting phosphate reabsorption.
• HHRH can present with hypercalcemia, potentially masking hypophosphatemia.

Purpose of the Study:

• To present a case of HHRH diagnosed in adulthood.
• To emphasize the diagnostic significance of hypophosphatemia in complex electrolyte imbalances.
• To illustrate the genetic basis and clinical features of HHRH.

Main Methods:

• Case report of a 21-year-old female with a history of nephrocalcinosis and intermittent hypercalcemia.
• Review of patient's medical history, including childhood presentation and investigations.
• Genetic testing confirming a homozygous SLC34A3 mutation (c.1483G>A, p.G495R).

Main Results:

• The patient presented with short stature, nephrocalcinosis, and recurrent nephrolithiasis.
• Persistent hypophosphatemia with phosphaturia and high-normal calcitriol were noted.
• Genetic confirmation of HHRH due to SLC34A3 mutation.
• Oral phosphate replacement normalized serum phosphate, calcium, and urine calcium.

Conclusions:

• HHRH diagnosis requires careful evaluation of hypophosphatemia, even with hypercalcemia.
• SLC34A3 mutations cause phosphate wasting, leading to rickets and hypercalciuria.
• This case underscores the importance of genetic testing for HHRH and appropriate phosphate management.