HCS should be recognized as a distinct thalassemia syndrome with a high risk of life-threatening anemia during febrile illnesses. HbH was not associated with an increased rate of severe anemia with infections and was managed without blood transfusions. Many patients with these disorders had mixed ethnic backgrounds, which highlights the need for extended newborn screening in populations that are traditionally considered to be at low risk for hemoglobin H disease.

No abstract

Increasing knowledge about thalassemia and its management among healthcare providers can improve patient outcomes and quality of life.

Many patients with beta-thalassemia major have depressed circulating levels of essential micronutrients. These nutritional deficiencies may be caused by an elevated requirement for these nutrients, increased excretion and/or because of inadequate dietary intake. However, the relationship between dietary intake and circulating levels of key nutrients has not been explored. Therefore, the aim of this prospective, cross-sectional study was to quantitate intake using gold standard dietary assessment techniques, as well as to assess circulating levels of key micronutrients in the fasted state in a contemporary sample of subjects with transfusion-dependent thalassemia (age >5 years). Dietary intake was determined with the Block©2005 3-day semi-quantitative food frequency questionnaire (NutritionQuest, Berkeley, CA) completed within 3 months of a pre-transfusion blood sample. Dietary intake (mg/day) was calculated relative to the Institute of Medicine recommendations for age and gender. Intake was then compared to circulating levels of vitamin C, 25-OH vitamin D, alpha & gamma-tocopherol, zinc, copper and selenium. The usage of nutritional supplements was documented. All results were analyzed using STATA (v 9.3, College Station, TX). Forty-one patients (20 male, mean age 28.3 ± 10.7 years) with an average BMI of 22.1 ± 5.2 kg/cm2 and pre-transfusion hemoglobin of 10.9 ± 1.5 g/dL were enrolled. The mean liver iron concentration (LIC) measured by Ferritometer was 13.5 ± 11.3 mg/g dry liver-weight. As has been observed previously, 14 to 30% of patients had low circulating levels of Zn, Cu, 25-OHD, vitamin C and alpha-tocopherol. No deficiencies were observed for selenium. Patients consumed on average 1555 ± 835 kcal/d (80% of estimated energy requirement) and 1.3 ± 0.9 g/kg protein. Average dietary intake was inadequate (less than estimated average requirement) for Ca, Zn, Cu, and vitamins C, D, and E. Among patients with low circulating micronutrient levels, 86% of those with low serum zinc also had low dietary zinc intake; similarly, 88% of those with low circulating copper also had low copper intake. Significant inverse correlations were observed between LIC and blood concentrations of the antioxidants vitamin C (r = -0.62), alpha-tocopherol (r = -0.37) and zinc (r = -0.35). The relationship between iron overload and vitamin C was further explored in a retrospective sample of 49 patients where simultaneous values of both measures were available (228 samples). Vitamin C level progressively decreased with increasing iron burden. The mean vitamin C level was 0.57 ± 0.47 mg/dL with LIC >15 mg/g compared with 1.06 ± 0.45 mg/dL when LIC was <7 mg/g (P <0.001). Serum ferritin levels were not associated with vitamin C deficiency (plasma concentration <0.4 mg/dL) at mild to moderate degrees of liver iron overload. However, with extreme iron overload (LIC >25 mg/g), ferritin levels were significantly greater in the presence of vitamin C deficiency (6545 ± 2597 ng/mL versus 4720 ± 1915 ng/mL, p=0.045). These data suggest that iron overload negatively influences blood levels of several micronutrients. Moreover, dietary intake is insufficient to support circulating levels of nutrients in optimally transfused thalassemia patients. Nutritional adequacy is essential for optimal health, and vitamin C status can impact chelation efficiency. Future research should consider nutritional supplementation and health outcomes in patients with transfusion-dependent thalassemia. Disclosures No relevant conflicts of interest to declare.

3198 Low bone mass has been described in as many as 60% of patients with thalassemia (Thal) and sickle cell disease (SCD). Bone pain is also frequently reported in each disorder, however few have explored the relationship between low bone mass and bone pain. The objectives of this study were to determine the prevalence of vertebral height abnormalities in patients with Thal and SCD at the Children's Hospital & Research Center, Oakland (CHRCO). The secondary objective was to evaluate the relationship between vertebral height abnormalities and low bone mass and patient assessed bodily pain. Methods: Data for this analysis were collected from two sources: the Thalassemia Clinical Research Network Pain Survey study and the CHRCO Clinical Bone Density database. The TCRN Pain study used a validated pain survey to collect data on 45 patients from CHRCO at multiple time points. Pain data was then analyzed along with bone mineral density (BMD) scans if performed within 6 months. BMD Z-scores were abstracted from the CHRCO database along with patient demographics. Full lateral spine scans conducted at the time of BMD scan were re-analyzed by one observer using the Vertebral Fracture Analysis (VFA) software (Hologic v12.6.1.), and scored according to Genant for vertebral abnormalities (crush, wedge, biconcavity, Grades 1 to 3). Results: A total of 254 VFA scans were re-analyzed from 93 patients with Thal (21.5 ± 10.7 yrs, 55% female), 45 SCD (38.1 ± 12.7 yrs, 61% Female) and 11 healthy control subjects (29.9 ± 10.2 yrs, 64% female). The patients with Thal were primarily Asian (78%), with 68.8% B-thal, 24%E-Bthal and 12.1% Hb H; while 98% of the SCD patients were Black, all HbSS. Patients with Thal were more likely to have low bone mass (any BMD Z-score ≧ −2.0) compared to those with SCD (73% vs. 33%, p<0.01). Of the patients with Thal who had VFA scans, 25 (26.9%) had at least one vertebral abnormality, compared to 16 (34.8 %) of the 45 patients with SCD (p=NS). SCD patients had significantly more vertebral abnormalities compared to healthy controls (p=0.04). However, a similar percentage of Thal patients had substantial vertebral height deficits (Grade 2 or 3; 15.1%) compared to those with SCD (13.3%). The average number of vertebrae with abnormalities within an individal scan was lower in Thal (1.6±0.2) compared to SCD (2.8 ± 0.4; p=0.003). Thal were more likely to have wedge-type deformities in the lumbar region, while SCD had biconcavity-type deformed vertebrae in the thoracic region. Of the patients with multiple VFA scans, 12 progressed toward vertebral abnormality during a 7 year period, all with Thal. The presence of a vertebral abnormality was positively related to age in Thal but not SCD (24.2 ± 1.2 vs. 20.6 ± 0.8 yrs, p=0.029) with a trend towards a relationship to low bone mass (p=0.12). Abnormal VFA was unrelated to gender and vitamin D level. In a sub-set of the Thal subjects who participated in the TCRN pain study, two-thirds reported significant pain within the past month, 16% severe and 27% reported pain localized in the lower back. However in the patients for which both VFA scans and pain studies were performed (n=32), bodily pain was not related to vertebral abnormalities. Discussion: A surprisingly high percentage of both SCD and Thal patients had significant vertebral abnormalities. In many cases the etiology of the observed abnormal morphology unclear but appears to be more developmental in SCD whereas in Thal a consequence of collapse secondary to inherent bone fragility and/or trauma. It is also yet to be determined if this phenomenon results from skeletal effects of the underlying disease or the various treatments (i.e., chelation toxicity). The prevalence of vertebral abnormality observed in this cohort of Thal patients (27%) is twice that previously reported from the TCRN (12%). The prevalence of vertebral abnormality by DXA scan has never before been reported in SCD. It is conceivable that the high rate of lower back pain in Thal is related to the observed abnormal vertebrae, however we were unable to explore this thoroughly given the small sample size. This study was limited by the absence of multiple VFA scans for all subjects and the discordance of a temporal relationship between the pain studies and VFA scans. Further research should focus on the clinical relevance of vertebral abnormalities and its etiology in these at risk patient populations. Disclosures: No relevant conflicts of interest to declare.

No abstract