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X-Linked Adrenoleukodystrophy

Overview

X-linked adrenoleukodystrophy (X-ALD) is a genetic disease cased by a mutation in the ABCD1 gene on the X chromosome, whose product is ALDP. There are different types of X-ALD with varying degrees of severity and age of onset.

ALDP

ALDP is an ATP-binding cassette (ABC) transport protein responsible for transporting saturated very long chain fatty acyl-CoAs into the peroxisome. ALDP is a half-transporter protein, requiring dimerization to be active. ALDP is related to other members of the ABCD subfamily including ALD-related protein (ALDRP, ABCD2), peroxosomal membrane protein 70 (PMP70, ABCD3), and PMP70-related protein (P70R, ABCD4). ALDP, ALDRP, and PMP70 are partially functionally redundant. ALDP is an integral peroxisomal membrane protein with the nucleotide binding site facing the cytoplasmic surface of the peroxisome.

Biomarkers

A prominent biomarker for X-ALD is the elevation of C24:0 and C26:0 very long chain fatty acids (VLCFA) in the plasma. However, the concentration of these VLCFA does not correlate with disease severity. C26:0 VLCFA does affect the structure and function of cell membranes. VLCFA are also incorporated into gangliosides, phosphatidylcholines, and cholesteryl esters to abnormally high degrees. C26:0-LPC is also elevated in the blood of individuals with X-ALD, so it is used as a biomarker in newborn screening.

Treatment

Lorenzo's oil can reduce the plasma level of C26:0 VLCFA, but cannot stop progression of the disease. Hematopoietic stem cell transplant can stop disease progression.

Updated on 230105