ODP310 Early Onset Adrenal Dysfunction in Infants with Adrenoleukodystrophy

Abstract Introduction X-linked adrenoleukodystrophy (ALD) is caused by mutations in the ABCD1 gene encoding the adrenoleukodystrophy protein that transports very-long-chain fatty acids (VLCFAs) to peroxisomes for degradation. An early manifestation is primary adrenal insufficiency (AI). Our clinic's protocol to screen for AI involves obtaining a morning cortisol and ACTH every 6 months, followed by cosyntropin (ACTH) stimulation testing if screening ACTH >100pg/mL or cortisol <5μg/dL. The peak incidence of AI is 3-10 years old, however there have been reports of infants as young as 4.5 months. 1 We present 2 asymptomatic boys with ALD demonstrating AI already at 6-7 months. Cases Patient 1 is a 6 month old full-term male with ALD detected on New York state (NYS) newborn screen and a hemizygous pathogenic variant, c.1201C>T, p. R401W in the ABCD1 gene. At 6 weeks, ACTH and cortisol levels were acceptable (table 1). After screening ACTH was elevated(175pg/mL) at 5 months, ACTH stimulation testing was performed at 6 months. Baseline cortisol was 11ug/dL and stimulated cortisol was insufficient at 13ug/dL. There was no hyperpigmentation, but were neurological concerns such as inability to roll over, left arm preference, and waning moro response. A brain MRI was recommended. Patient 2 is a 7 month old full-term male with ALD detected on NYS newborn screen and a hemizygous pathogenic variant, c.1661G>A (p. R554H) in the ABCD1 gene. At 6 weeks, ACTH and cortisol levels were acceptable (table 2). At 7 months, ACTH was elevated (120.7pg/mL). ACTH stimulation testing was performed with baseline cortisol of 6.9ug/dL and insufficiently stimulated cortisol of 13.5ug/dL. Neurological evaluation was normal. Because of inadequate rises in cortisol to ACTH stimulation, stress dosing hydrocortisone was recommended for both patients. Discussion These infants with early onset adrenal dysfunction raise the question of whether the peak incidence of AI is earlier than previously thought. This would not be surprising as VLCFAs were found to accumulate in fetal adrenal glands. Our findings further support the need for widespread newborn screening for ALD, followed by routine adrenal screening consistent with published guidelines to avoid adrenal crisis. In a case series of 2 patients with ALD and early onset AI, the reported mutations were p. R660W and p. R401Q. 1 In patient 1, a mutation at position 401 of the ALD protein was also reported, which stresses the importance of registries to correlate genotypes and phenotypes. Early onset adrenal disease has not yet been correlated with early neurologic disease. However, the neurological changes noted in patient 1 raise this concern and highlight the importance of multidisciplinary clinics with endocrinology and neurology. Sources: 1. Eng, L., & Regelmann, M. O. (2019). Early Onset Primary Adrenal Insufficiency in Males with Adrenoleukodystrophy: Case Series and Literature Review. The Journal of pediatrics,211, 211–214. https://doi.org/10.1016/j. jpeds.2019. 04. 021 Presentation: No date and time listed