Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: Clinical, laboratory and genetic findings
Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: Clinical, laboratory and genetic findings
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DOI：
10.1530/eje.0.1370040
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发表时间：
1997-07-01
影响因子：
5.8
通讯作者：
Hanefeld, F
中科院分区：
文献类型：
--
作者：
Korenke, GC;Roth, C;Hanefeld, F
X-连锁肾上腺皮质营养不良(ALD)是男性Addison病最常见的病因之一，其特征是超长链脂肪酸的β-氧化损伤，并与ALD基因突变导致膜转运蛋白缺陷有关。ALD患者的内分泌和神经症状具有显著的多样性，ALD基因突变与不同的神经表型之间没有明显的相关性，目前还没有关于ALD内分泌症状和ALD基因的数据发表。我们报告了34个家系55例ALD患者的内分泌、临床、实验室和分子遗传学资料。在33例患者中观察到肾上腺功能不全的内分泌症状，其中20例表现为脑性ALD或肾上腺髓神经病的额外神经症状。12例患者出现孤立的神经症状，9例患者既没有内分泌症状，也没有神经症状。来自32个家庭的50名患者(包括9对兄弟)检测到ALD基因突变(n=28)。未发现ALD基因突变与内分泌功能障碍的相关性。然而，我们发现所有兄弟的内分泌表型都是一致的(两组皮质醇合成减少，七组正常)，而四组表现出不协调的神经表型。到目前为止，除了ALD基因突变以外的未知遗传因素对ALD的内分泌表型的干扰可能比对ALD的神经表型的干扰更强。
X-linked adrenoleucodystrophy (ALD) has been shown to be one of the most frequent causes of Addison's disease in men, It is characterized by an impaired peroxisomal beta-oxidation of very long chain fatty acids and is associated with mutations of the ALD gene resulting in a defective peroxisomal membrane transport protein. There is a striking variability of endocrinological and neurological symptoms in patients with ALD, with no clearly evident correlation between mutations of the ALD gene and the different neurological phenotypes, No data on endocrinological symptoms and the ALD genotype have been published so far.We report endocrinological, clinical, laboratory and molecular genetic data from 55 patients with ALD from 34 families. Endocrinological symptoms of adrenal insufficiency were observed in 33 patients, 20 of whom showed additional neurological symptoms of cerebral ALD or adrenomyeloneuropathy. Isolated neurological symptoms were seen in 12 patients; in nine patients there were neither endocrinological nor neurological symptoms.Mutations of the ALD gene (n = 28) were detected in 50 patients (including nine sets of brothers) from 32 families. No correlation was found between the ALD gene mutation and endocrinological dysfunction. However, we found that all sets of brothers were concordant for the endocrinological phenotype (cortisol synthesis was reduced in two sets and normal in seven sets), whereas four sets showed a discordant neurological phenotype. As yet unknown hereditary factors other than mutations within the ALD gene may interfere with the endocrinological phenotype more strongly than with the neurological phenotype of ALD.