Autosomal Dominant Hypophosphatemic Rickets (ADHR) Presenting in an Adult Patient without Growth Restriction or Skeletal Deformities

Program: Abstracts - Orals, Poster Previews, and Posters
Session: FRI 368-390-Metabolic Bone Disease Case Reports (posters)
Friday, April 1, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board FRI 370
Su Ah Bae*1 and Abid Yaqub2
1University of Cincinnati College of Medicine, Cincinnati, OH, 2University of Cincinnati, Cincinnati, OH
Background: Autosomal-dominant hypophosphatemic rickets (ADHR) results from missense mutations in gene encoding FGF-23 resulting in impaired cleavage of FGF-23 molecule and associated with renal phosphate wasting. ADHR has variable penetrance and age onset. 

Clinical case: A 22 -year old female was referred to our Endocrine clinic with a two year history of gradually progressive proximal muscle pain and weakness involving both upper and lower extremities. She had normal childhood and pubertal growth with no dental or skeletal abnormalities on exam or radiological studies. There was no reported family history of rickets or osteomalacia. Further laboratory work-up revealed normal Calcium 9.1 mg/dL (8.6-10.3 ),low serum phosphorus 1.4mg/dL(2.5-5.0), normal PTH 47.9 pg/mL (7.5-53.5 ), increased alkaline phosphatase 243 U/L (34-104 ), low 25 OH Vitamin D 16.7ng/mL(30.0-100 ), normal 1, 25 hydroxy Vitamin D 39 pg/ml (18-78) and elevated FGF-23 580 RU/mL (44 - 215  ). Urine phosphate excretion was found to be increased confirming renal phosphate wasting.  MRI of pelvis showed insufficiency fractures involving the medial aspect of bilateral femoral necks and right ischium. Due to low serum phosphorus, high urinary phosphate excretion and increased FGF-23 level with no skeletal or radiological bone deformities and absence of pertinent family history, a provisional diagnosis of tumor induced osteomalacia (TIO) was favored. However an extensive search for a primary mesenchymal tumor including cross sectional imaging studies,  Octreotide scan with SPECT imaging, and F-18 FDG PET/CT scan failed to reveal any  focal tumor. Her lower extremity pain progressed. She underwent bilateral femoral neck pinning to decrease fracture risk . After almost one year of follow up with us, the patient told us that she just found out from her paternal grandmother, who she does not see often, that she had some paternal relatives with rickets. We sent for genetic testing which showed that she had a FGF-23 mutation. Testing for PHEX and DMP-1 were negative. The results are consistent with diagnosis of ADHRs.  Patient’s symptoms improved significantly on Calcitriol and oral phosphorus replacement therapy with normalization of phosphorus level. 

Conclusion: ADHR has variable penetrance and age of onset. Diagnosis of ADHR should be considered even in adults without any skeletal deformities or obvious family history of the disease.

(1) Econs MJ. Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder. J Clin Endocrinol Metab. 1997 Feb;82(2):674-81.(2) Goldsweig BK, Carpenter TO. Hypophosphatemic Rickets: Lessons from Disrupted FGF23 Control of Phosphorus Homeostasis. Curr Osteoporos Rep (2015) 13:88–97

Nothing to Disclose: SAB, AY

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