X-linked Adrenoleukodystrophy in a 20-Year-Old Male With an ABCD1 Gene Mutation: First Case From Pakistan

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disease characterized by genetic mutation of the ABCD1 gene. This gene encodes for transmembrane adrenoleukodystrophy protein (ALDP). Defective ALDP protein results in the accumulation of a very long chain fatty acid (VLCFA) within certain tissues and plasma. X-ALD can initially present as Addison's disease (primary adrenal insufficiency) as the accumulation of VLCFA most importantly occurs in the adrenal gland. Our 20-year-old male patient, a known case of Addison's disease, presented with vision loss, neurologic symptoms, and psychiatric issues. Neurologic symptoms included poor concentration and memory, while psychiatric problems included primarily depressive disorder and mild psychotic behavior. His Addison's disease was secondary to X-ALD. Still, he was diagnosed late due to a lack of awareness of X-ALD and a lack of resources for genetic testing in Pakistan. Therefore, the purpose of this case report is to spread knowledge and understanding of X-ALD, so that it can be ruled out as the potential cause of adrenal insufficiency in young patients, particularly males diagnosed with Addison's disease. Moreover, if the patient presents with Addison's disease and psychiatric issues, they should be tested to rule out X-ALD.

Addison’s Disease: Diagnosis and Management Strategies

“… 46 , 47 Awareness of ABCD1 mutations in young males with AD might help the neurologic outcome. 48 Two novel mutations were reported in a 27-year-old male harboring ABCD1 mutation c.874_876delGAG (p.Glu292del), and a 31-year-old man with c.96_97delCT (p.Tyr33Profs*161) pathogenic variant. 49 X-linked adrenoleukodystrophy (the most common peroxisomal disorder in the majority carrying ABCD1 mutations) has been addressed in a longitudinal study involving, among others, ABCD1 sequencing (including whole exome sequencing): 16.7% (N = 2 males) of the 22 patients (male to female ratio of 12:10) carrying ABCD1 variants developed AD after a median of 2.28 years.…”

“… Lu 43 Case report 1 male child with lipoid CAH StAR heterozygous mutation (c.772C>T/c.562C>T) Phadte 44 3 Indian patients with P450 side-chain cleavage deficiency and AD 3 novel pathogenic CYP11A1 variants Homozygous p.Gly423Asp Heterozygous p.Arg151Trp/p.Pro104Ser Homozygous c.1351 C > T (p.Arg451Trp) Ali 45 Case report A 17-y-old male with AD since the age of 9 Tri-allelic heterozygous CYP11A1 mutation + digenic STAR loss-of-function variants: c.465+1G>A p.(E99K). Gupta 46 Pediatric male case report with X-linked adrenoleukodystrophy AD onset before cerebral involvement Wiersma 47 Case report 11-y-old boy with 1 DM + AD Confirmation of X-linked adrenoleukodystrophy Ghori 48 Case report A 20-y-old male with AD confirmed with ABCD1 mutation First case from Pakistan Dong 49 Case series (a 27-y-old, and a 31-y-old male) with ABCD1 variants 2 novel mutations: c.874_876delGAG (p.Glu292del) c.96_97delCT (p.Tyr33Profs*161) Chen 50 Longitudinal study Screening protocol at birth for ...…”