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An unusual presentation of X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a rare genetic condition caused by mutations in the ABCD1 gene that result in accumulation of very long chain fatty acids (VLCFAs) in various tissues. This leads to demyelination in the CNS and impaired steroidogenesis in the adrenal cortex and testes. A 57-y...

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Autores principales: Suryawanshi, Avinash, Middleton, Timothy, Ganda, Kirtan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655831/
https://www.ncbi.nlm.nih.gov/pubmed/26609365
http://dx.doi.org/10.1530/EDM-15-0098
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author Suryawanshi, Avinash
Middleton, Timothy
Ganda, Kirtan
author_facet Suryawanshi, Avinash
Middleton, Timothy
Ganda, Kirtan
author_sort Suryawanshi, Avinash
collection PubMed
description X-linked adrenoleukodystrophy (X-ALD) is a rare genetic condition caused by mutations in the ABCD1 gene that result in accumulation of very long chain fatty acids (VLCFAs) in various tissues. This leads to demyelination in the CNS and impaired steroidogenesis in the adrenal cortex and testes. A 57-year-old gentleman was referred for the assessment of bilateral gynaecomastia of 6 months duration. He had skin hyperpigmentation since 4 years of age and spastic paraparesis for the past 15 years. Physical examination findings included generalised hyperpigmentation (including skin, buccal mucosa and palmar creases), blood pressure of 90/60 mmHg, non-tender gynaecomastia and bilateral hypoplastic testes. Lower limb findings were those of a profoundly ataxic gait associated with significant paraparesis and sensory loss. Primary adrenal insufficiency was confirmed and investigations for gynaecomastia revealed normal testosterone with mildly elevated luteinising hormone level and normal prolactin. The combination of primary adrenal insufficiency (likely childhood onset), partial testicular failure (leading to gynaecomastia) and spastic paraparesis suggested X-ALD as a unifying diagnosis. A serum VLCFA panel was consistent with X-ALD. Subsequent genetic testing confirmed the diagnosis. Treatment with replacement doses of corticosteroid resulted in improvement in blood pressure and increased energy levels. We have reported the case of a 57-year-old man with a very late diagnosis of X-ALD manifested by childhood onset of primary adrenal insufficiency followed by paraparesis and primary hypogonadism in adulthood. Thus, X-ALD should be considered as a possibility in a patient with non-autoimmune primary adrenal insufficiency and neurological abnormalities. LEARNING POINTS: Adult patients with X-ALD may be misdiagnosed as having multiple sclerosis or idiopathic spastic paraparesis for many years before the correct diagnosis is identified. Screening for X-ALD with a VLCFA panel should be strongly considered in male children with primary adrenal insufficiency and in male adults presenting with non-autoimmune primary adrenal insufficiency. Confirmation of a genetic diagnosis of X-ALD can be very useful for a patient's family as genetic testing enables detection of pre-symptomatic female heterozygotes who can then be offered pre-natal testing to avoid transmission of the disease to male offsprings.
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spelling pubmed-46558312015-11-25 An unusual presentation of X-linked adrenoleukodystrophy Suryawanshi, Avinash Middleton, Timothy Ganda, Kirtan Endocrinol Diabetes Metab Case Rep Unique/Unexpected Symptoms or Presentations of a Disease X-linked adrenoleukodystrophy (X-ALD) is a rare genetic condition caused by mutations in the ABCD1 gene that result in accumulation of very long chain fatty acids (VLCFAs) in various tissues. This leads to demyelination in the CNS and impaired steroidogenesis in the adrenal cortex and testes. A 57-year-old gentleman was referred for the assessment of bilateral gynaecomastia of 6 months duration. He had skin hyperpigmentation since 4 years of age and spastic paraparesis for the past 15 years. Physical examination findings included generalised hyperpigmentation (including skin, buccal mucosa and palmar creases), blood pressure of 90/60 mmHg, non-tender gynaecomastia and bilateral hypoplastic testes. Lower limb findings were those of a profoundly ataxic gait associated with significant paraparesis and sensory loss. Primary adrenal insufficiency was confirmed and investigations for gynaecomastia revealed normal testosterone with mildly elevated luteinising hormone level and normal prolactin. The combination of primary adrenal insufficiency (likely childhood onset), partial testicular failure (leading to gynaecomastia) and spastic paraparesis suggested X-ALD as a unifying diagnosis. A serum VLCFA panel was consistent with X-ALD. Subsequent genetic testing confirmed the diagnosis. Treatment with replacement doses of corticosteroid resulted in improvement in blood pressure and increased energy levels. We have reported the case of a 57-year-old man with a very late diagnosis of X-ALD manifested by childhood onset of primary adrenal insufficiency followed by paraparesis and primary hypogonadism in adulthood. Thus, X-ALD should be considered as a possibility in a patient with non-autoimmune primary adrenal insufficiency and neurological abnormalities. LEARNING POINTS: Adult patients with X-ALD may be misdiagnosed as having multiple sclerosis or idiopathic spastic paraparesis for many years before the correct diagnosis is identified. Screening for X-ALD with a VLCFA panel should be strongly considered in male children with primary adrenal insufficiency and in male adults presenting with non-autoimmune primary adrenal insufficiency. Confirmation of a genetic diagnosis of X-ALD can be very useful for a patient's family as genetic testing enables detection of pre-symptomatic female heterozygotes who can then be offered pre-natal testing to avoid transmission of the disease to male offsprings. Bioscientifica Ltd 2015-11-03 2015 /pmc/articles/PMC4655831/ /pubmed/26609365 http://dx.doi.org/10.1530/EDM-15-0098 Text en © 2015 The authors This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en_GB) .
spellingShingle Unique/Unexpected Symptoms or Presentations of a Disease
Suryawanshi, Avinash
Middleton, Timothy
Ganda, Kirtan
An unusual presentation of X-linked adrenoleukodystrophy
title An unusual presentation of X-linked adrenoleukodystrophy
title_full An unusual presentation of X-linked adrenoleukodystrophy
title_fullStr An unusual presentation of X-linked adrenoleukodystrophy
title_full_unstemmed An unusual presentation of X-linked adrenoleukodystrophy
title_short An unusual presentation of X-linked adrenoleukodystrophy
title_sort unusual presentation of x-linked adrenoleukodystrophy
topic Unique/Unexpected Symptoms or Presentations of a Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655831/
https://www.ncbi.nlm.nih.gov/pubmed/26609365
http://dx.doi.org/10.1530/EDM-15-0098
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