Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report

Area of Science:

• Biochemistry
• Genetics
• Pediatric Endocrinology

Background:

• Primary adrenal insufficiency (PAI) in children is rare but life-threatening, with diverse causes including inherited metabolic disorders.
• Peroxisomal dysfunctions are rare causes of PAI, with adrenal involvement in ACOX1 deficiency poorly understood.
• X-linked adrenoleukodystrophy is a known cause, but other peroxisomal diseases like ACOX1 deficiency present diagnostic challenges.

Purpose of the Study:

• To report a case of ACOX1 deficiency presenting with PAI in a child.
• To highlight the variable adrenal involvement in ACOX1-related pseudo-neonatal adrenoleukodystrophy.
• To emphasize the importance of routine endocrine screening in peroxisomal disorders.

Main Methods:

• Case report of a three-year-old girl with developmental delay and neurological regression.
• Biochemical analysis of plasma very-long-chain fatty acids.
• Whole-exome sequencing to identify pathogenic variants in ACOX1.
• Endocrine evaluation including ACTH, cortisol, electrolytes, and plasma renin activity (PRA).
• Adrenal imaging.

Main Results:

• Diagnosis of pseudo-neonatal adrenoleukodystrophy confirmed by homozygous pathogenic variant in ACOX1.
• Endocrine evaluation revealed elevated ACTH and low cortisol, indicating PAI.
• Patient exhibited no classical signs of adrenal failure like hyperpigmentation or electrolyte imbalance.
• Adrenal imaging showed atrophy; hydrocortisone replacement was initiated with good response.

Conclusions:

• ACOX1 deficiency can present with variable adrenal involvement, expanding its known phenotype.
• The absence of typical symptoms underscores the need for routine hormonal screening in children with peroxisomal diseases.
• Early detection of endocrine dysfunction is crucial to prevent adrenal crises and understand peroxisomal β-oxidation disorders.