Skip to Main Content


Markers of disease progression and response to therapy for HHRH

A recent survey of all known kindreds with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) identified a number of unmet therapeutic needs for individuals with this rare disorder (Dasgupta et al. 2014). For example, while the rachitic bone disease of HHRH responds well to oral phosphate supplementation, it is completely unknown whether adult height is affected and if enthesopathies can develop as they do in X-linked hypophosphatemia (XLH). It is also not clear if the renal phosphate-leak persists throughout life, whether therapy can be stopped just as is done in cases of autosomal dominant hypophosphatemic rickets (ADHR), and if HHRH predisposes individuals to accelerated bone loss during adulthood. In addition, no biomarkers exist for the myopathy often seen in individuals with severe hypophosphatemia, and renal calcifications observed with HHRH often delay therapy with oral phosphate supplements because, despite the benefit of improved hypercalciuria with therapy, the resulting phosphaturia may worsen this complication of HHRH. Given the clear need to carefully characterize HHRH, we are currently establishing disease progression, symptoms, biochemical and imaging biomarkers for HHRH, and adverse event information of standard therapies for HHRH. The lab’s long-term goal is to conduct trials for innovative therapies of hypophosphatemic rickets, osteomalacia and myopathy.

Recent Publications

Bergwitz C, Miyamoto K Hereditary Hypophosphatemic Rickets with Hypercalciuria Pathophysiology, Clinical Presentation, Diagnosis and Therapy, Pflugers Arch. 2018 Aug 14. doi: 10.1007/s00424-018-2184-2. [Epub ahead of print] Review. PMID: 30109410R12.

Dasgupta D, Wee MJ, Reyes M, Li Y, Simm PJ, Sharma A, Schlingmann K-P, Janner M, Biggin A, Lazier J, Gessner M, Chrysis D, Tuchman S, Baluarte HJ, Levine MA, Tiosano D, Insogna K, Hanley DA, Carpenter TO, Ichikawa S, Hoppe S, Konrad M, Sävendahl L, Munns CF, Lee H, Jüppner H and Bergwitz C Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis. JASN April 3, 2014, doi: 10.1681/ASN.201310108

Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Jüppner H. SLC34A3 Mutations in Patients with Hereditary Hypophosphatemic Rickets with Hypercalciuria Predict a Key Role for the Sodium-Phosphate Cotransporter NaPi- IIc in Maintaining Phosphate Homeostasis. Am J Hum Genet. 2006;78(2):179-92.