Severe Hypophosphatemic Bone Disease Associated with Elevated Serum FGF23 Level in an Adult Patient with Epidermal Nevus Syndrome

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 376
Luciana Pinto Valadares*1, Daniel Rocha Carvalho2, Alessandra de La Rocque Ferreira2 and Adriana Lofrano-Porto3
1Hospital Sarah, Sarah Network of Rehabilitations Hospitals; University of Brasilia, Faculty of Health Sciences, Molecular Pharmacology Laboratory., Brasilia, Brazil, 2Hospital Sarah, Sarah Network of Rehabilitations Hospitals, Brasilia, Brazil, 3University of Brasilia, Brasilia, DF, Brazil
Background: Epidermal nevus syndrome (ENS) is a rare congenital disorder characterized by epidermal nevus and abnormalities in multiple systems. Hypophosphatemic rickets rarely occurs in ENS and is related to increased levels of FGF23, though the source of FGF23 overproduction is still debated. Its natural history is unknown, although it is reported that hypophosphatemia and osteomalacia tend to resolve or improve as the skeleton matures. We described an adult patient with ENS and longstanding hypophosphatemia and osteomalacia associated with an elevated serum FGF23 level. 

Clinical case: A 27 year-old man was referred to the Endocrinology Clinic after a diagnosis of hypophosphatemic rickets in early childhood, when he was treated with oral phosphorus and calcitriol, with suboptimal control. After puberty, he lost follow-up and remained untreated, with worsening of bone disease. He was the youngest of an offspring of twelve, born after an uneventful pregnancy of healthy non-consanguineous parents. Since birth, multiple right-side linear epidermal nevi along Blaschko’s lines were noted, which progressed lifelong. He also had right hemihypoplasia and dysplastic bone lesions on skeletal radiographs. He had no apparent neurologic abnormality, but was restricted to a wheelchair and developed severe restrictive lung disease consequent to thoracic deformity. He had an extremely low serum phosphorus level  (0.94mg/dL, normal range [NR] 2.5-4.8), associated with very low serum 25-alpha–hydroxi-vitamin D (6.39 ng/mL) and mild hypocalcemia (8.4mg/dL, NR 8.8-11.0).  PTH  and alkaline phosphatase were high (347.8pg/mL, NR 10-69 and 396U/L, NR53-128U/L, respectively). Phosphate tubular resorption fraction was 55%, indicating urinary phosphate loss. Serum FGF23 was elevated (169.7kRU/L, NR 34 - 96kRU/L). Skeletal X-ray revealed innumerous deformities and severe osteomalacia. Calcitriol and phosphorous replacement were re-introduced with partial biochemical improvement. A skin biopsy of a lesion in the trunk was consistent with epidermal nevus, with a positive immunostaining for FGF23. However, no expression of FGF23 mRNA was detected by qPCR, using GAPDH and B2M genes as control.

Conclusion:  This case illustrates the occurrence of FGF23 mediated–hypophosphatemia in ENS, which persisted during adulthood leading to severely disabling osteomalacia. Although expression of FGF23 in the skin lesion was not detected, positive immunostaining for FGF23 was shown. This finding may be associated with interactions of FGF23 and ubiquitously expressed  isoforms of FGF receptors in skin (1,2). Recently, somatic activating RAS mutations have been described in this syndrome (3). Further studies are needed to clarify the molecular defects underlying the phenotypic features of this case.

(1)Ramon I et al., Eur J Endocrinol 2010;162(1):1–10. (2)Yu X et al., Endocrinology 2005;146(11):4647–56. (3) Lim YH et al., Hum Mol Genet 2014; 23(2):397–407

Nothing to Disclose: LPV, DRC, ADLRF, AL

*Please take note of The Endocrine Society's News Embargo Policy at