Unexpected SLC34A3 rickets in a case of suspected distal myopathy

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH), caused by SLC34A3 gene mutations, is characterized by hypophosphatemia, hypercalciuria, and low PTH levels. While rickets and skeletal deformities are common, HHRH also poses a significant risk for chronic kidney disease (CKD) due to nephrocalcinosis and recurrent kidney stones. Here, we describe a patient with mild skeletal deformities, who was diagnosed with HHRH during adolescence after undergoing whole genome sequencing (WGS) for suspected myopathy. Despite hypophosphatemia and low PTH, the patient had normal calcium levels and no nephrocalcinosis or kidney stones. X-rays showed mild metaphyseal changes consistent with rickets. While muscle weakness and pain are noted in X-linked hypophosphatemic rickets, neurological symptoms in HHRH tend to be milder. We present a patient with an unexpected homozygous likely pathogenic variant in the SLC34A3 gene. This case underscores the importance of distinguishing between skeletal, nephrological, and neurological conditions for accurate diagnosis, effective treatment, and genetic counseling.