ESPE Abstracts

Introduction: Fanconi anemia (FA) is a rare genetic disease that presents with aplastic anemia. Around 60% have short stature (SST), with a mean height of -2.2 SD. However, studies assessing the etiology of SST not having reached relevant conclusions.

Aim: Our aim was to evaluate the clinical features and endocrine status in relationship to SST in patients with FA.

Methods and Patients: A cross-sectional study was carried-out between 2019-2020 in 31 pediatric patients (19 females) with FA. Auxological assessment, biochemical analysis, study of the hypothalamic-pituitary axis and an MRI of the hypothalamic-pituitary area were performed.

Results: At birth, the mean weight was -1.62 SD (IQR: -2.1; -1.2), being lower than -2 SD in 34.6% (9/26) of the patients. The mean length was -1.67 SD (IQR: -2.36; -0.88), being lower than -2 SD in 41.6% (10/26). The mean age at first evaluation was 9.7 ± 4.2 years [Tanner I (n = 21), Tanner II (n = 1), Tanner III (n = 1), Tanner IV (n = 2), Tanner V (n = 6)]. Mean height was -2.07 SD (IQR: -2.96, -1.09) and was below -2 SD in 54.8% (17/31), with 86% (19/22) being shorter than their target height (TH). The mean BMI was -0.74 SD (± 0.83).Six female patients reached final height and were -2.3 SD (± 0.82) from their TH. Hematopoietic cell transplant (HCT) was performed in 16 patients. The attributable fraction of exposure to HCT in patients with SST was 42% [CI95% (71-85)], P > 0.05. No correlation was found between height and anthropometry at birth. Only 5 patients had endocrinological alterations: 2 had adrenal insufficiency secondary to corticosteroid treatment, 2 had hypergonadotropic hypogonadism after transplantation, and 1 had GH deficiency. Serum levels of IGF-1 and IGFBP-3 were within the normal range in all patiens, with the exception of GH-deficient patient. The GH/IGF axis was assessed in 23 patients, observing a decrease in staniocalcin 1 (STC1) [311.3 IQR(1166.7-554.9)] and STC2 [23.2 IQR(18.5-26.9)] and an increase in free IGF-1 levels [6.4 ng/ml IQR(2.95-10.3)] in pubertal patients compared to healthy controls. Pituitary morphology was assessed in 9 patients. The volume of the pituitary gland was normal [0.45SD (IQR: -0.21; 0.75)], except in the patient with GH deficiency, who had a volume of -2.98SD with ectopic neurohypophysis.

Conclusions: Short stature is an integral feature of FA but does not seem to be related to a GH deficiency. However, an alteration in the peripheral regulation of the GH/IGF axis cannot be excluded.