Iatrogenic Vitamin D Deficiency in a Patient with Gorlin Syndrome: The Conundrum of Photoprotection

Abstract

Acute and chronic UV exposure is an important risk factor leading to photocarcinogenesis, photoimmuno suppression and photoaging (1, 2). Patients with Gorlin syndrome (GS) harbour a hereditary predisposition to develop basal cell carcinomas (BCC) and are, therefore, advised that effective sun protection is essential and can help reduce skin cancer risk (1-4). On the other hand, adherence to strict sunprotection habits can result in vitamin D deficiency, which has been demonstrated in many patients with GS (2, 3). Vitamin D deficiency is associated with an increased risk of osteomalacia, bone fractures, autoimmune diseases, cancer and cardiovas cular disease (1). CASE REPORTHere, we report a 54yearold man with GS who was admitted to our hospital for surgical treatment of multiple BCC (Fig. 1). Characteristic features of GS were present in the form of multiple BCC since youth, palmoplantar pits, an odontogenic cyst, calcification of the falx cerebri, and positive family history (5). DNA analysis by multi plex ligationdependent probe amplification revealed a novel heterozygous deletion of exons 11 and 12 within the PTCH1 gene, leading to a frame shift and premature termination codon. Moreover, the patient's medical his tory revealed that within the past decades, multiple bone fractures had occurred after minimal trauma, suggesting a bone calcification disorder. The patient reported of his strict photoprotection habits by daily textile and cosmetic sun protection measures as well as trying to avoid sun exposure. Laboratory workup including parameters of bone turnover and metabolism showed serum 25(OH)D levels of < 4 ng/ml, far below the normal range (30-70 ng/ml), elevated alkaline phosphatase and low serum phosphate concentrations. Serum calcium, parathyroid hormone and vitamin A, E and K concentrations were within normal ranges. Dualenergy Xray absorptiometry (DEXA) was consistent with severe osteoporosis ac cording to the WHO classification, with a mean T-score of -3.6 measured from the hip (Fig. 2). Based on these observations, we concluded that the patient suffered from a disorder of bone mineralisation caused by vitamin D deficiency. Substitution therapy was initiated with a single dose of intramuscularly administered vitamin D3 derivative (cholecalciferol 100,000 IU) followed by longterm daily oral substitution of 2,000 IU of vitamin D3. The 25(OH)D level was within the normal range 3 months after initiation of therapy.Vitamin D deficiency has been described in GS pa tients and is thought to be related to strict sun protection habits (1-3). The time of vitamin D measurement in our patient was spring (April), where probands usually have higher vitamin D levels than during winter (2), but they were still below the detection limit of the labora tory test. Normal serum levels of the other lipophilic vitamins (vitamins A, E, K) argue against an intestinal malabsorption disorder or an imbalanced overall nu tritional vitamin supply in our patient. There were no signs of renal or hepatic insufficiency which could have...

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Basal cell naevus syndrome: an update on genetics and treatment

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