Primary adrenal insufficiency (PAI) in childhood is a rare and potentially life-threatening condition that may arise from defects in adrenal steroidogenesis, adrenal dysgenesis, ACTH resistance, autoimmune mechanisms, or inherited metabolic disorders. Among the latter, peroxisomal dysfunctions represent a rare cause. Although X-linked adrenoleukodystrophy is a well-recognized etiology, adrenal involvement in other peroxisomal diseases, such as ACOX1 deficiency, remains poorly defined. We report a three-year-old girl with global developmental delay, epilepsy, bilateral sensorineural hearing loss, and progressive neurological regression. Biochemical analyses revealed abnormal plasma very-long-chain fatty acids profile, suggesting a peroxisomal disorder. Whole-exome sequencing identified a homozygous pathogenic variant (c.1478+2T>A) in ACOX1, confirming the diagnosis of pseudo-neonatal adrenoleukodystrophy. During hospitalization for a urinary tract infection, endocrine evaluation revealed markedly elevated plasma ACTH (529 pg/mL) and low serum cortisol (8.62 µg/dL), while Na, K, and PRA were within normal limits. Adrenal imaging was consistent with atrophy. Hydrocortisone replacement was initiated with good clinical response. Notably, the patient had no classical signs of adrenal failure such as hyperpigmentation or electrolyte imbalance. This case provides additional evidence that ACOX1-related Pseudo-neonatal adrenoleukodystrophy may be associated with variable adrenal involvement, expanding the phenotypic spectrum of the disorder. The absence of typical clinical manifestations highlights the importance of routine hormonal screening in children with peroxisomal diseases, even in the absence of overt adrenal symptoms. Early recognition of endocrine dysfunction can prevent life-threatening adrenal crises and offers valuable insight into the broader pathophysiology of peroxisomal β-oxidation disorders.
Turan et al. (Mon,) studied this question.