ESPE Abstracts

Background: Autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; APS-1) is a disorder arising from mutations in the autoimmune regulator (AIRE) gene, that lead to the development of circulating autoreactive T-cells and deficiency of regulatory T-cells. Multiple manifestations, such as primary adrenocortical insufficiency, and their treatments may disturb growth in children with APECED. However, no previous data on prepubertal growth in children with APECED has been reported.

Methods: Fifty-nine children [30 (51%) girls] from a national APECED cohort were followed from 1952 to 2021. Height and weight development, progression of APECED, duration of glucocorticoid treatment, and infections were retrospectively collected from birth until the end of prepuberty. Birth size z-scores were calculated according to the exact gestational age in preterm pregnancies and according to 40+0 weeks in full-term pregnancies (≥37+0 weeks). Height, weight-for-height, and mid-parental target height z-scores were calculated according to national growth references.

Results: The mean birth weight was 3340 g (z-score -0.80) and 12 patients (20%) were small for gestational age (z-score <-2.0). Of the 59 children with APECED, 38 (64%) had a height z-score below 0 during the whole prepuberty, and 7 (12%) had a z-score below -2.0. Height measurements were compared between three time points (birth, diagnosis of first endocrinopathy, and end of prepuberty) and in relation to mid-parental target height. Birth length z-score (mean, -0.67) did not significantly differ from mid-parental height (mean, -0.59) but was shorter than the population mean. From birth, the mean height z-score declined progressively being -1.34 at the time of first endocrinopathy and -1.86 by the end of prepuberty. Meanwhile, the weight-for-height z-score increased from -0.80 at birth to -0.06 at the time of first endocrinopathy and +0.12 at the end of prepuberty. The height z-score at the end of prepuberty correlated negatively with the total number of manifestations [r (95% CI), -0.27 (-0.49 – -0.011), P= 0.041], but no correlation was found with the duration of glucocorticoid treatment or the number of infections. Altogether, eight patients were treated for growth hormone deficiency from the mean age of 9.6 years; they were shorter than the others at the end of prepuberty (mean height z-score, -2.80 vs. -1.71, P= 0.03).

Conclusions: Children with APECED are shorter than their peers already at birth and their height z-score progressively declines during childhood and prepuberty. APECED predisposes children to short stature and growth disturbances, warranting careful follow-up during childhood to ensure optimal height gain.