E-Poster Presentation ESA-SRB-ANZBMS 2021

A young woman with childhood onset bone pain and late diagnosis of Hereditary Hypophosphatemic Rickets with Hypercalciuria (#337)

Divya Namboodiri 1 , Varun Manoharan 1 2 , Namson Lau 1 2
  1. Liverpool Hospital, NSW, Australia
  2. South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive condition. Implicated genes produce missense mutations which disrupt sodium-phosphate co-transport, resulting in renal phosphate wasting1 2. Clinically HHRH causes nephrolithiasis /calcinosis, bone pain, rickets, lower extremity deformities and short stature1.

 

We report on a 43-year-old lady with symptoms from childhood, with complex osteomalacia, limb deformities & rickets.  Through to young adulthood, she had multiple bilateral femoral shaft osteotomies and surgeries. She migrated to Australia in her late 20s and was referred to endocrinology with initial management of intravenous bisphosphonates for chronic vertebral insufficiency fractures seen on imaging. Prior to the correct diagnosis, biochemistry serially showed low to normal phosphate, normal to mildly suppressed PTH, markedly elevated 1,25 hydroxyvitamin D levels(1,25(OH)2D), bone turnover markers in the upper range of normal to mild elevation; 24-hour urine tests showed intermittent hypercalciuria and hyperphosphaturia. Serum fibroblast growth factor 23 (FGF23) levels were low on both measurements. 

Estimated prevalence of HHRH is 1:250,0002. Unlike the more common X-linked hypophosphatemia, it is a FGF23-independent disorder2. HHRH is marked by renal phosphate wasting and appropriately elevated 1,25(OH)2D levels, which in turn increase intestinal calcium absorption and reduce PTH-dependent calcium-reabsorption in the distal renal tubules. Clinically this causes hypercalciuria and other manifestations.

Our index patient is one of eight children of consanguineous Iraqi & Syrian parents, but the only member affected.  Due to clinical suspicion of a hereditary bone syndrome, she was referred to clinical genetics and a homozygous (pathological) variant within the SLC34A3 gene with missense mutation on both alleles eventually confirmed.

HHRH is rare, so underrecognized with diagnosis often delayed2. Current treatment recommendation is long-term phosphate supplements2.  Active vitamin D metabolites are contraindicated, as it worsens hypercalciuria2. For our patient, high dose phosphate supplementation alleviated all her residual bone symptoms.

 

 

  1. 1. Bergwitz C, Miyamoto KI. Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy. Pflugers Arch 2019;471(1):149-63. doi: 10.1007/s00424-018-2184-2 [published Online First: 2018/08/16]
  2. 2. Colazo JM, Reasoner SA, Holt G, et al. Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) Presenting with Genu Valgum Deformity: Treatment with Phosphate Supplementation and Surgical Correction. Case Rep Endocrinol 2020;2020:1047327. doi: 10.1155/2020/1047327 [published Online First: 2020/07/23]