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Abstract Disclosure: A. Deswal: None. A. Dwarakanathan: None. Introduction: X Linked Adrenal Leukodystrophy (X-ALD) is a rare hereditary genetic disorder of impaired peroxisomal metabolism due to a defective transmembrane protein, ADLP. Defective ADLP impairs transport of VLCFA-CoA esters across cytosol into peroxisomes leading to build-up of toxic VLCFA in the cells. X-ALD is caused by mutation in ABCD1 gene, located on X chromosome, which codes for ADLP. It has a broad clinical spectrum including Cerebral ALD, Adrenomyeloneuropathy and Adrenocortical insufficiency. X-ALD has a general prevalence of 1 in 17,000 newborns. Approximately 80% of males with X-ALD develop primary adrenal insufficiency in their lifetime. It can be diagnosed by measuring VLCFA levels in plasma , checking for ABCD1 gene mutation or by doing Brain MRI (depending upon phenotypical presentation ). Case presentation: We report a case of a 23 year old man who had primary adrenocortical insufficiency subtype of X-ALD. His mother was a carrier of ABCD1 gene mutation. He himself tested hemizygous for ABCD1 gene. He came to our office for a follow up visit after an episode of adrenal crisis for which he was hospitalized. He was started on replacement therapy with prednisone and fludrocortisone. Over the next couple of years, he was diagnosed with diabetes mellitus with initial HbA1C of 8.8%. GAD antibody test for type I DM came out negative. His diabetes was managed with metformin and pioglitazone( later discontinued) .By the age of 25,he was found to have polyposis of colon. He tested positive for APC gene mutation . He underwent a J pouch surgery . He also developed PICA aneurysm. Discussion: X-ALD is a hereditary progressive disease with no association between genetic and phenotypic presentations. Adrenal insufficiency type is usually the first to present. Cerebral ALD is typically diagnosed between the ages of 3-18 presenting as psychiatric illness. Myelopathy typically starts by middle age and involves the spinal cord, causing the affected individuals to develop gait disturbances , bladder and bowel dysfunction, with severe mobility dysfunction by 5th-6th decade of life. We present a unique case of a young man with adrenal insufficiency type of X-ALD who also developed gastrointestinal pathology. Per our literature review, X-ALD has not been seen associated with APC gene mutations or colon carcinomas . Pathology behind XLD revolves around ABCD1 gene mutaion causing VLCFA accumulation in plasma, fibroblasts, adrenal glands, oligodendrocytes , astrocytes etc. Whereas FAP involves APC gene mutation which affects the intestinal epithelial cells leading to their apoptosis and polyp formation. X-ALD and FAP are disorders of two different gene mutations with varied clinical presentations. But the question arises regarding finding of APC gene mutation in a patient with ABCD1 gene mutation that if it is a mere co-incidence or common mutation pathway linking these two disorders exists. Presentation: 6/2/2024
Deswal et al. (Tue,) studied this question.