Abstract
X-linked adrenoleukodystrophy is a common X-linked recessive peroxisomal disorder caused by the mutations in the ABCD1 gene. In this study, we analyzed 19 male patients and 9 female carriers with X-linked adrenoleukodystrophy in South China. By sequencing the ABCD1 gene, 13 different mutations were identified, including 7 novel mutations, and 6 known mutations, and 1 reported polymorphism. Mutation c.1180delG was demonstrated to be de novo mutation. 26.3 % (5/19) patients carried the deletion c.1415_16delAG, which may be the mutational hot spot in South China population. In addition, 73.7 % (14/19) patients were type of childhood cerebral adrenoleukodystrophy, 26.3 %(5/19) were in Addison only. Half of the childhood cerebral adrenoleukodystrophy patients had the adrenocortical insufficiency preceded the onset of neurological symptoms. Furthermore, 5 of 19 cases underwent hematopoietic stem cell transplantation. Our data showed that hematopoietic stem cell transplantation performed at an advanced stage of the cerebral X- linked adrenoleukodystrophy would accelerate the progression of the disease. Good clinical outcome achieved when hematopoietic stem cell transplantation performed at the very early stage of the disease.
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References
Aubourg P, Wanders R (2013) Peroxisomal disorders. Handb Clin Neurol 113:1593–1609
Berger J, Gärtner J (2006) X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects. Biochim Biophys Acta 1763:1721–1732
Bezman L, Moser AB, Raymond GV, Rinaldo P et al (2001) Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol 49:512–517
Chiu HC, Liang JS, Wang JS, Lu JF (2006) Mutational analyses of Taiwanese kindred with X-linked adrenoleukodystrophy. Pediatr Neurol 35:250–256
Dubey P, Raymond GV, Moser AB, Kharkar S et al (2005) Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr 146:528–532
Engelen M, Kemp S, de Visser M, van Geel BM et al (2012) X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphan J Rare Dis 7:51–65
Ferrer I, Aubourg P, Pujol A (2010) General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain Pathol 20:817–830
Habekost CT, Pereira FS, Vargas CR et al. (2015) Progression rate of myelopathy in X-linked adrenoleukodystrophy heterozygotes. Metab Brain Dis
Hwu WL, Chien YH, Liang JS, Lee WT et al (2003) Adrenoleukodystrophy initially diagnosed as idiopathic Addison’s disease in two patients: the importance of early testing. J Formos Med Assoc 102:510–513
Kemp S, Berger J, Aubourg P (2012) X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta 1822:1465–1474
Korenke GC, Roth C, Krasemann E, Hüfner M et al (1997) Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings. Eur J Endocrinol 137:40–47
Miller WP, Rothman SM, Nascene D, Kivisto T et al (2011) Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood 118(7):1971–1978
Moser HW (1997) Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 120:1485–1508
Mosser J, Lutz Y, Stoeckel ME, Sarde CO et al (1994) The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. Hum Mol Genet 3:265–271
Moser HW, Mahmood A, Raymond GV (2007) X-linked adrenoleukodystrophy. Nat Clin Pract Neurol 3:140–151
Nascimento M, Rodrigues N, Espada F, Fonseca M (2012) Adrenoleukodystrophy: a forgotten diagnosis in children with primary Addison’s disease. BMJ Case Rep
Niu YF, Ni W, Wu ZY (2013) ABCD1 mutations and phenotype distribution in Chinese patients with X-linked adrenoleukodystrophy. Gene 522:117–120
Pan H, Xiong H, Wu Y, Zhang YH et al (2005) ABCD1 gene mutations in Chinese patients with X-linked adrenoleukodystrophy. Pediatr Neurol 33:114–120
Pereira Fdos S, Matte U, Habekost CT, de Castilhos RM et al (2012) Mutations, clinical findings and survival estimates in South American patients with X-linked adrenoleukodystrophy. PLoS One 7, e34195
Peters C, Charnas L, Tan Y, Ziegler RS et al (2004) Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood 104:881–888
Polgreen LE, Chahla S, Miller W, Rothman S et al (2011) Early diagnosis of cerebral X-linked adrenoleukodystrophy in boys with Addison’s disease improves survival and neurological outcomes. Eur J Pediatr 170:1049–1054
Shapiro E, Krivit W, Lockman L, Jambaqué I et al (2000) Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet 356:713–718
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This research was supported by a grant from the National Key Technology and Program of China (grant No. 2012BAI09804).
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Min-yan Jiang and Yan-na Cai contributed equally to this work.
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Jiang, My., Cai, Yn., Liang, Cl. et al. Clinical, biochemical, neuroimaging and molecular findings of X-linked Adrenoleukodystrophy patients in South China. Metab Brain Dis 30, 1439–1444 (2015). https://doi.org/10.1007/s11011-015-9717-6
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DOI: https://doi.org/10.1007/s11011-015-9717-6