Alstr(o)m综合征一例

患者男,16岁,因多饮、多尿、多食、体重下降1年,加重伴发热、鼻衄3天入院.1年前,患者无明显诱因下出现多饮、多尿,日饮水量达3 000ml左右,1年来体重下降约12.5 kg,未系统诊治.3 d前,患者出现流涕,发热,体温最高达38.2℃,伴少量鼻衄,自服消炎药后体温降至37.5℃,但仍有少量鼻衄,就诊于我院门诊，查空腹血糖16.2 mmol/L,尿糖(++++),尿(++++),遂以"糖尿病酮症"收入院.既往史:8年前视力逐渐减退,5年前双目失明,否认头颅外伤和肾脏病史,足月顺产,父母非近亲结婚,否认家族中有类似患者.体检:血压110/80mm Hg(1 mm Hg=0.133 kPa),身高167 cm,体重57.5 kg,体重指数(BMI)20.6 kg/m2，步态正常,智力无明显异常,皮肤较粗糙,颈部及腋下轻度黑棘皮样改变,全身可见数处色素斑,未见紫纹,内眦倒置,轻度眼震,双目失明,听力下降,乳房发育TannerⅡ期,第2性征发育正常,睾丸长径3.0 cm,阴茎长7.0cm,心界向左扩大,其余体检未见异常.     

Alström综合征2例并文献复习

该文报道2例分别因“糖尿病”和“低钾血症”就诊,且均有糖尿病、胰岛素抵抗、黑棘皮病、视网膜色素变性、高脂血症、肝肾功能损伤的患者临床资料,并进行全外显子基因测序,结果显示,2例患者分别携带 ALMS1基因c.2179dupT和c.10825C>T、c.2433dupA和c.11042dupT复合杂合突变,综...     

Alstr(o)m综合征的研究进展

Alstr(o)m综合征是一种隐性的单基因细胞纤毛遗传性疾病,由ALMS1基因突变引起,其典型特征为视锥-杆体细胞营养不良、听力损失、儿童腹型肥胖、胰岛素抵抗和高胰岛素血症、2型糖尿病、高甘油三酯血症、成年期身材矮小、心肌病和进行性肺、肝、肾功能障碍.ALMS1基因缺陷包括插入、删除和无义突变,导致蛋白质截短.ALMS1蛋白位于所有受疾病影响的纤毛细胞中心体、基底部和细胞溶质组织.具有维护纤毛功能和结构的作用,另外在细胞内运输、纤毛信号通路调节、细胞分化等方面也发挥作用.但ALMS1确切的致病机制不明.Alstr(o)m综合征不同年龄阶段临床特征不同,初步诊断依赖于临床症状,但确诊依赖于ALMS1基因检测.目前,Alstr(o)m综合征尚无根治方法,主要治疗措施局限于临床症状的对症处理和生活质量的改善,因此必须继续研究疾病的分子致病机制,进而明确基因治疗靶点,开辟个性化治疗道路.     

Alstr(o)m综合征临床特征分析及2例报告

目的 Alstr(o)m综合征是一种罕见的常染色体隐性遗传疾病,临床表现多样.通过探讨Alstr(o)m综合征的主要临床特征及实验室结果,以增强对该病的认识.方法 采用回顾性分析,对本科收治的2例患者及国内报道的7例Alstr(o)m综合征患者从临床特征、实验室结果、发病年龄进行综合分析.结果 9例患者均有视力、听力障碍,8例患者有身材矮小及自幼肥胖、7例有黑棘皮症、6例有糖尿病、高尿酸血症、4例有心脏损害；5例患者有肝功能损害及高甘油三酯血症,男性患者有性腺功能减低,1例患者有尿崩症及精神症状.9例患者主要症状出现的平均年龄:眼部病变、视神经萎缩为6.0岁,神经性耳聋为10.3岁,2型糖尿病出现在14.5岁.结论 Alstr(o)m综合征多以视力障碍为首发表现,继后常伴有神经性耳聋、幼时胖、身材矮小、黑棘皮症、糖尿病等；实验室结果常有肝功能损害、高甘油三酯等.这些发现可提高对该病早期正确诊断和恰当的处理.     

Alstr?m Syndrome and Cecal Volvulus in 2 Siblings

Alström syndrome (ALMS1, MIM 203800) is a rare, autosomal recessively inherited monogenic condition caused by mutations in the ALMS1 gene located on the short arm of chromosome 2. ALMS1 is a multisystem condition characterized by childhood onset of blindness, dilated cardiomyopathy, sensorineural hearing loss, renal failure, fibrotic lung disease, and metabolic abnormalities, including hypertriglyceridemia, liver steatosis, insulin resistance, type 2 diabetes mellitus, and obesity. We describe 2 siblings with ALMS who presented with the potentially life-threatening condition of acute cecal volvulus, an association not previously reported. Cecal volvulus may, therefore, represent a significant new feature of the Alström syndrome.     

Lffler's心内膜炎一例

患者畅××,女,53岁(住院号257909),因乏力、发热、左胸持续性隐痛三周于1985年10月5日入院。在院外查心电图示ST-T改变、嗜酸性细胞计数5,500/mm~3、骨髓像正常而转我院。复查嗜酸性细胞计数44/mm~3,拟为“心内膜下心肌梗塞”乃收入院。入院体检血压120/80mmHg、浅表淋巴结不大,颈静脉无怒张。心界向两侧扩大,心率74次/分,     

Alström syndrome with acute pancreatitis: a case report

We report the case of a 21-year-old female with Alstr?m syndrome who also suffered from acute pancreatitis of obscure manifestation. The patient had underlying cone-rod dystrophy of the retinas, nystagmus, obesity, progressive sensorineural hearing impairment, diabetes mellitus, and hypertriglyceridemia, compatible with the clinical diagnosis of Alstr?m syndrome. Serial examinations showed liver dysfunction and pancreatitis. In treating a patient with poor communication (i.e. cone-rod dystrophy and hearing impairment) suffering from acute illness, understanding the underlying disease and the potential for pancreatitis with hypertriglyceridemia is necessary. It is also a challenge to treat a patient with multiple system involvement. In conclusion, Alstr?m syndrome is a disease of systemic multi-organ involvement, and hepatic disease and pancreatitis, possibly due to dyslipidemia, appear to be manifestations of Alstr?m syndrome.     

Alström syndrome: insights into the pathogenesis of metabolic disorders

Genetic causes of obesity include the ciliopathies Alstr?m syndrome and Bardet-Biedl syndrome. In these disorders, mutations cause dysfunction of the primary cilium, an organelle involved in intracellular and intercellular sensing and signaling. Alstr?m syndrome is an autosomal-recessive disorder caused solely by mutations in ALMS1. By contrast, Bardet-Biedl syndrome is caused by mutations in at least 14 genes involved in primary cilium function. Despite equivalent levels of obesity, patients with Alstr?m syndrome are more likely than those with Bardet-Biedl syndrome to develop childhood type 2 diabetes mellitus (T2DM), suggesting that ALMS1 might have a specific role in β-cell function and/or peripheral insulin signaling pathways. How mutations in genes that encode proteins involved in primary cilium function lead to the clinical phenotypes of these syndromes is being revealed by work in mutant mouse models. With the aid of these models, insights are being obtained into the pathogenic mechanisms that underlie obesity, insulin resistance and T2DM. Research into ciliopathies, including Alstr?m syndrome and Bardet-Biedl syndrome, should lead not only to improved treatments for individuals with these genetic disorders, but also to improved understanding of the cellular pathways involved in other common causes of obesity and T2DM.     

New Alström syndrome phenotypes based on the evaluation of 182 cases

BACKGROUND: Alstr?m syndrome is a recessively inherited genetic disorder characterized by congenital retinal dystrophy that leads to blindness, hearing impairment, childhood obesity, insulin resistance, and type 2 diabetes mellitus. We provide new details on cardiologic, hepatic, gastrointestinal, urologic, pulmonary, and neurobehavioral phenotypes in Alstr?m syndrome and describe the histopathologic findings in 5 individuals. METHODS: We obtained data on 182 patients from clinical examinations, medical record reviews, standardized questionnaires, and personal interviews with physicians and parents. RESULTS: Dilated cardiomyopathy occurred in 60% of patients. Age at onset was either during infancy, often before vision disturbances were noted, or in adolescence or adulthood. There is a risk of recurrence of infantile cardiomyopathy. Hyperinsulinemia (92%) developed in early childhood and progressed to type 2 diabetes mellitus in 82% of those older than 16 years. Hypertriglyceridemia (54%) precipitated pancreatitis in 8 patients. Urologic dysfunction and gastrointestinal disturbances occurred in 48% and 35% of patients, respectively. Fifty-three percent of patients had persistent pulmonary symptoms. Neurologic symptoms in 20% of patients included clonic tic and absence seizures. Developmental motor or language delays were observed in 46% of patients. Fibrotic infiltrations of multiple organs, that is, kidney, heart, liver, lung, urinary bladder, gonads, and pancreas, were observed. CONCLUSIONS: The wide-ranging and complex spectrum of phenotypes reported herein broadens those previously described for Alstr?m syndrome. These findings will aid physicians in making an early and accurate diagnosis and will help effect appropriate monitoring and treatment.