Elevated serum serotonin levels in patients with Osteoporosis-Pseudoglioma Syndrome [poster]

Abstract

Background: Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder characterized by congenital blindness and childhood osteoporosis, due to mutations in LRP5. Approximately 40 children with OPPG have been reported, 9 by our group(1). Studies in the mouse model of OPPG revealed elevated serum levels of gut-derived serotonin, normally inhibited by LRP5. Normalization of serum serotonin corrected the bone phenotype. Serum serotonin levels have been reported in only 4 humans with OPPG (one age 52 years(2), and three ages 23, 13 and 11 years(3)). The purpose of this study was to measure serum serotonin in patients with OPPG and to evaluate for correlations between age, bone turnover and BMD Z-score. Study Design: Fasting serum serotonin was measured in 6 OPPG patients, ranging in age from 29 days to 17 years, by Nichols (HPLC) in 2, and by Mayo Lab (LC/MS/MS) in 4. These patients are Old Order Mennonites, members of 2 related nuclear families. All OPPG patients were off bisphosphonates at the time of the study for 4-11 months; four of them had previously been treated with bisphosphonates, and one also with teriparatide. Urine N-telopeptide (NTX) was measured on a morning void. Results: Serum serotonin levels are shown for 6 OPPG patients bellow. There was no correlation between serotonin and NTX (p=0.23), or with Z-scores at the total hip or lumbar spine (p=0.89, p=0.95). There was a significant correlation between serotonin and age (p=0.03). Discussion: We found mild elevations in serum serotonin in 6 patients with OPPG, including 4 patients under age 10, the youngest levels reported to date. We found a positive correlation between age and serotonin levels, as found in the mouse model of OPPG. The degree of elevation that we found (1.01-2.46) was lower than that seen by Yadav (4.0-5.0)(3) and similar to Saarinem (2.27)(2). However, we did not have internal controls and used upper level of normal as a reference, which could account for this difference. We found no correlation between serotonin and NTX or DXA Z-scores; however, 4 of 6 patients had been treated with bisphosphonates, which lowered NTX and improved Z-scores. Studies are needed in OPPG to determine whether normalization of serum serotonin in humans would correct bone phenotype.