Unexpected Endocrine Features and Normal Pigmentation in a Young Adult Patient Carrying a Novel Homozygous Mutation in the POMC Gene
Unexpected Endocrine Features and Normal Pigmentation in a Young Adult Patient Carrying a Novel Homozygous Mutation in the POMC Gene
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DOI：
10.1210/jc.2008-1164
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发表时间：
2008-12-01
影响因子：
5.8
通讯作者：
Leger, Juliane
中科院分区：
文献类型：
--
作者：
Clement, Karine;Dubern, Beatrice;Leger, Juliane
内容：阿黑皮素原（POMC）是五种生物活性肽的前体，包括垂体前叶产生的ACTH和下丘脑产生的α-MSH。POMC基因的突变在儿童中被描述，导致多效性综合征，包括继发性皮质醇减少症、严重肥胖和皮肤和毛发色素沉着的可变变化。目的：我们描述了一名女性患者的北非血统，纯合子的移码突变的POMC基因（6922 InsC）会损害所有黑皮质素肽的产生，并且与新的临床特征相关。从出生到18岁的反复临床调查presented. Results：ACTH缺乏症诊断在出生时。在2岁之前，暴食和肥胖变得明显，并迅速进展[体重指数（BMI）Z评分，2岁时+7 SD，13岁时+9.7 SD; 18岁时BMI为50 kg/m2]。在青春期，患者发生了促生长激素、促性腺激素和甲状腺轴的改变，需要激素替代。令人惊讶的是，没有明显的色素沉着特征;无论是头发的颜色还是皮肤反射率的测量都不能区分患者和未受影响的家庭成员。然而，头发色素的化学分析表明，增加生产的pheomelanin和eumelanin.Conclusion：POMC的分子遗传异常应始终考虑在早发性肾上腺皮质功能不全和肥胖症患者，即使在存在正常的色素沉着和多种垂体激素异常。（临床内分泌代谢杂志93：4955-4962，2008）
Context: Proopiomelanocortin (POMC) is the precursor to five biologically active peptides, including ACTH produced in the anterior pituitary and alpha-MSH produced in the hypothalamus. Mutations that inactivate the POMC gene have been described in children, causing a pleiotropic syndrome that includes secondary hypocortisolism, severe obesity, and variable changes in skin and hair pigmentation.Objective: We describe a female patient of North African ancestry, homozygous for a frameshift mutation in the POMC gene (6922InsC) that impairs the production of all melanocortin peptides, and that is associated with novel clinical features. Repeated clinical investigations from birth to age 18 yr are presented.Result: ACTH deficiency was diagnosed at birth. Hyperphagia and obesity became apparent before 2 yr of age and rapidly progressed [body mass index (BMI) Z-score, +7 SD at 2 yr, +9.7 SD at 13 yr; BMI, 50 kg/m(2) at 18 yr). At puberty, the patient developed alterations in the somatotropic, gonadotropic, and thyroid axes necessitating hormonal replacement. Surprisingly, there were no obvious pigmentary features; neither the hair color nor measurements of skin reflectance distinguished between the patient and unaffected family members. However, chemical analysis of hair pigment revealed increased production of both pheomelanin and eumelanin.Conclusion: Molecular genetic abnormalities of POMC should always be considered in patients with early onset adrenal insufficiency and obesity, even in the presence of normal pigmentation and multiple pituitary hormone anomalies. (J Clin Endocrinol Metab 93: 4955-4962, 2008)