{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T01:28:35Z","timestamp":1782264515822,"version":"3.54.5"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>X-linked adrenoleukodystrophy (X-ALD) is a rare inborn error of the peroxisomal metabolism caused by pathologic variants in the ATP-binding cassette transporter type D, member 1 (ABCD1) gene located on the X-chromosome. ABCD1 protein, also known as adrenoleukodystrophy protein, is responsible for transport of the very long chain fatty acids (VLCFA) from cytoplasm into the peroxisomes. Therefore, altered function or lack of the ABCD1 protein leads to accumulation of VLCFA in various tissues and blood plasma leading to either rapidly progressive leukodystrophy (cerebral ALD), progressive adrenomyeloneuropathy (AMN), or isolated primary adrenal insufficiency (Addison\u2019s disease). We report two distinct single nucleotide deletions in the ABCD1 gene, c.253delC [p.Arg85Glyfs*18] in exon 1, leading to both cerebral ALD and to AMN phenotype in one family, and c.1275delA [p.Phe426Leufs*15] in exon 4, leading to AMN and primary adrenal insufficiency in a second family. For the latter variant, we demonstrate reduced mRNA expression and a complete absence of the ABCD1 protein in PBMC. Distinct mRNA and protein expression in the index patient and heterozygous carriers does not associate with VLCFA concentration in plasma, which is in line with the absence of genotype\u2013phenotype correlation in X-ALD.<\/jats:p>","DOI":"10.3390\/ijms24065957","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T07:09:31Z","timestamp":1679468971000},"page":"5957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Two Single Nucleotide Deletions in the ABCD1 Gene Causing Distinct Phenotypes of X-Linked Adrenoleukodystrophy"],"prefix":"10.3390","volume":"24","author":[{"given":"Katrin A.","family":"Dohr","sequence":"first","affiliation":[{"name":"Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvija","family":"Tokic","sequence":"additional","affiliation":[{"name":"Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Gastager-Ehgartner","sequence":"additional","affiliation":[{"name":"Research Unit of Analytical Mass Spectrometry, Cell Biology and Biochemistry of Inborn Errors of Metabolism, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Stojakovic","sequence":"additional","affiliation":[{"name":"Clinical Institute of Medical and Chemical Laboratory Diagnostics, University Hospital Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Dumic","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3203-1325","authenticated-orcid":false,"given":"Barbara","family":"Plecko","sequence":"additional","affiliation":[{"name":"Division of General Paediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja K.","family":"Dumic","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1096\/fj.08-110866","article-title":"The human peroxisomal ABC half transporter ALDP functions as a homodimer and accepts acyl-CoA esters","volume":"22","author":"Roermund","year":"2008","journal-title":"FASEB J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1210\/endrev\/bnaa013","article-title":"The Changing Face of Adrenoleukodystrophy","volume":"41","author":"Zhu","year":"2020","journal-title":"Endocr. 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