Sirs, Linear nevus sebaceous syndrome (LNSS) is a neuroectodermal disorder, which may be associated with hypophosphatemic rickets in childhood. The pathogenesis of hypophosphatemia is unclear and has been attributed to increased levels of fibroblast growth factor-23 (FGF-23)[1]. We report a patient with LNSS, hypophosphatemic rickets; and high blood levels of FGF-23, immunoglobulin (Ig) E, and parathormone (PTH). A 5-year-old boy, son a non-consanguineous marriage, was referred for increasing skin lesions on face and arms since birth and lower limb deformities. The child was developmentally normal for age. He had clinical and radiological features of rickets and multiple, linear, hyperpigmented plaques following the morphological pattern of Blaschko lines over the right side of his scalp, face, ear, and arms. Investigations showed normal blood levels of creatinine, calcium, and 25-hydroxyvitamin D; low phosphate (1.8–2.0 mg/dl); and raised alkaline phosphatase and parathormone (PTH). There was evidence of phosphate wasting, with low tubular maximum for phosphate reabsorption per glomerular filtration rate (TmP/GFR)(Table 1). Contrast-enhanced computed tomography (CT) of the head was normal. Following a diagnosis of LNSS with hypophosphatemic rickets, he was treated with phosphate supplements at a dose of 750–1,000 mg and alpha calcidiol 0.25 µg every day. The patient reported recently with poor compliance with medications, increasing bony deformities, and enlarging cutaneous nevi. Investigations showed similar blood findings, with low levels of phosphate and TmP/GFR and markedly raised PTH (Table 1). Serum IgE level was 179 IU/ml (normal< 60 IU/ml), and FGF-23 was 1,265 pg/ml (normal 10–60 pg/ml). Skeletal survey showed features of osteopenia with rickets and multiple radiolucent cysts over the left third metacarpal, ulna, and femur, as well as bilateral radii. Biopsy of the nevus showed epidermal papillomatous sebaceous gland hyperplasia with clusters of primordial hair follicles, suggesting LNSS. Immunohistochemistry for FGF-23 was negative (courtesy Dr. Fukumoto, University of Tokyo). Ultrasonography of the neck and Tc99m sestamibi scan for parathyroid glands showed no evidence of adenoma. Whole-body positron emission tomography for tumors was negative. The patient is receiving phosphate supplements (1.5 g/day) and alpha calcidiol (0.5 µg/day); phosphate levels range between 2.6–2.8 mg/dl.

This patient with LNSS is interesting because we found hypophosphatemia but markedly high levels of PTH and FGF-23, an association that is rarely reported. Aschinberg et al. reported the association between rickets and LNSS, with improvement of musculoskeletal symptoms and hypophosphatemia after excision of the nevus [3]. Infusion of extract from the nevus resulted in reduced renal tubular reabsorption of phosphate in animals [3]. The putative phosphatonin was FGF-23 based on demonstration of its elevated blood levels in a patient with LNSS [1]. Hoffman et al. also showed that treatment with octreotide and