真核翻译始动因子2-a激酶3基因突变致Wolcott-Rallison综合征1例

目的 对Wolcott - Rallison综合征的临床特征及遗传发病机制进行研究.方法 选取临床诊断为Wolcott - Rallison综合征的患儿及其父母为研究对象,运用PCR技术扩增患儿家系真核翻译始动因子2-α激酶3(EIF2AK3)基因的17个外显子区,用DNA直接测序技术,对患儿家系EIF2AK3基因的17个外显子进行基因突变分析.结果 在患儿及其父亲EIF2AK3基因的第9外显子区发现了1个杂合突变(1798A/T),氨基酸序列分析显示这个突变是一种无义突变,可导致EIF2AK3第532位C氨基酸残基形成终止密码子( C532STOP),形成1个532氨基酸残基组成的截短蛋白.患儿母亲EIF2AK3基因未发现相应突变(1798T/T).结论 在中国儿童中,EIF2AK3基因突变可导致Wolcott - Rallison综合征发生.     

Cohen's Syndrome with Diabetes Mellitus

We report a case of 12-year-old girl with Cohen's syndrome (CS) associated with diabetes mellitus (DM). She had the characteristic facies, with a short philtrum, an open-mouth appearance, prominent maxillary central incisors, high palate, mild maxillary hypoplasia and micrognathia. Other features included truncal obesity, short stature, mental deficiency, small hands and feet, and accentuated thoracic kyphosis. She had been hypotonic during the neonatal and early infantile periods. Laboratory examinations showed hyperglycemia and glucosuria. HbA_l and HbA₁ c levels were raised. A 75-g oral glucose tolerance test (OGTT) showed glucose intolerance consistent with DM, but there was a normal level of urinary C-peptide. There were no islet cell antibodies (ICAs) and no history of ketoacidosis. This is the first reported case of CS with non-insulin-dependent diabetes mellitus (NIDDM).     

Characterization of Diabetes Mellitus in Japanese Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is frequently associated with marked obesity and diabetes mellitus (DM). Although the overall frequency of DM in PWS ranges from 7–20%, there is only limited data available on Japanese patients. This study evaluated five factors associated with DM in PWS: 1) frequency, 2) age of onset, 3) risk factors, 4) long-term complications and 5) treatment. Sixty-five patients, ranging in age from 10 to 53 yr, were studied retrospectively. The frequency of DM in patients over 10 yr of age was 26.2% (17/65 patients). The age of DM onset ranged from 10 to 29 yr with a median age of 15 yr. The body mass index (BMI) was significantly higher in the DM group in comparison with the non-DM group. The number of patients using growth hormone (GH) in the DM group was significantly lower than the number that did not. Proteinuria (urinary excretion of albumin/creatinine at spot collection: U-Alb/Cr ≥300 mg/gCr) was observed in 1/17 patients (5.9%), microalbuminuria (U-Alb/Cr 30–300 mg/gCr) was observed in 4/17 patients (23.5%) and nonproliferative retinopathy was observed in 2/17 patients (11.8%). Among oral hypoglycemic agents, alpha-glucosidase inhibitors (α-GI) were most often used in our patients (10/17, 58.8%). Eleven out of 17 patients (64.7%) had been treated with insulin.     

Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (DIDMOAD Syndrome): A Clinical Study in Two Sudanese Families

ABSTRACT. Four Sudanese children with DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) are reported. They were two boys (aged 15 and 16 years) in one family and a boy and a girl (aged 16 and 6 years, respectively) in another family. Diabetes mellitus was first to appear (at 3–8 years) followed by deafness and visual failure; and the disease ended fatally in one patient (aged 20 years). In the other three, diabetes insipidus was confirmed using water deprivation test for 8 hours. The maximum urine osmolality ranged between 131–523 mOsm/kg, whereas the corresponding plasma osmolality ranged between 315–332 mOsm/kg. Slight further improvement in urine concentration was observed in 2 of the patients following the use of desmopression (DDAVP, 20 μg intranasally). Intravenous pyelography, voiding cystourethrography and ultrasound revealed severe bilateral hydronephrosis, dilated ureters and distended bladder without vesicoureteral reflux in the three patients. With the high rate of consanguinity prevalent in North Africa and the Middle East, we recommend examining children who present with diabetes mellitus in this region for features of DIDMOAD syndrome.     

Report of a Japanese Girl with Marfan Syndrome Associated with Insulin-Dependent Diabetes Mellitus

A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she Received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.     

Diabetes Mellitus in Friedreich's Ataxia

In a clinical study of Friedreich's ataxia diabetes mellitus was found in nine of 50 typical cases. The mean age of the diabetes onset was 21.9 years and the clinical type was a severe ketosis-prone diabetes. In 18 non-diabetics an intravenous glucose tolerance test was performed. One of these cases was disclosed to be a prediabetes. The mean rate of glucose disappearance was normal. Serum lipid analysis showed a slight elevation in non-diabetics and a higher in diabetics. The frequency of diabetes mellitus, including the prediabetic case, was 20%. Owing to the low age of the cases and as the glucose tolerance test was performed only in about half of the non-diabetics, this figure was estimated to be lower than the total frequency in Friedreich's ataxia. A brief survey of the literature is given, and the aetiology of diabetes mellitus in Friedreich's ataxia is discussed. The marked frequency of a known heredity to diabetes in the diabetic cases lends support to the hypthesis of a genetic aetiology. The possibility of an interplay between the defective genes of the two diseases is assumed. The pronouncedly vegetative syndrome occurring in Friedreich's ataxia suggests the possibility of a central nervous factor, though this can hardly be a primary cause of the diabetes.     

儿童糖尿病198例

目的 探讨儿童糖尿病(DM)的临床特点,为临床诊治提供理论依据.方法 对1999年1月-2009年3月在本院住院的198例DM患儿的临床表现和实验室检查进行回顾性临床分析.结果 198例DM患儿中,男97例,女101例.均为首诊病例;发病高峰年龄为5～6岁及9～11岁;首诊例数逐年增加,2008年较1999年增加了3.7倍;其中1型糖尿病(T1DM) 174例(占88.9％),2型糖尿病7例(占3.5％),新生儿DM 14例(占7.1％),其他3例(占1.5％).首诊的TlDM患者中,酮症酸中毒(DKA)的发生率为42.0％;发病前有感染史者55例,与无感染史者比较,DKA的发生率有统计学差异(P＜0.01).有DM家族遗传史者23例.并甲状腺功能亢进症2例;并暂时性甲状腺功能减低症31例;并肝功能异常30例,肾功能异常12例,血脂异常48例,尿蛋白阳性27例.糖化血红蛋白为(12.0±1.8)％;共分析了25例T1 DM患者的自身抗体,胰岛细胞抗体阳性率为28％,胰岛素自身抗体的阳性率为20％,谷氮酸脱羧酶自身抗体(GADA)阳性率为72％.结论 首诊的儿童DM逐年增加,以T1DM为主;新生儿DM增加明显;DKA是T1DM患者就诊的重要原因;首诊的T1DM者中,感染是发生DKA的重要诱因;儿童DM常合并暂时性甲状腺功能减低症、肝肾功能异常及血脂异常;糖尿病自身抗体中GADA的阳性率最高.     

1型糖尿病并低三碘甲状腺氨酸综合征201例

目的探讨1型糖尿病(T1DM)及糖尿病酮症酸中毒(DKA)患儿并低三碘甲状腺氨酸(T3)综合征的临床特点。方法采用放射免疫分析法检测91例T1DM并DKA患儿(DKA组)及110例单纯T1DM患儿(非DKA组)血清T3、甲状腺素(T4)、促甲状腺激素(TSH)水平,观察2组T3、T4下降例数及水平,并将DKA组分为轻、中、重3个亚组,观察不同组别中甲状腺激素变化特点。结果 DKA组易发生T3、T4下降,DKA组T3[(0.54±0.51)μg.L-1]、T4[(5.65±2.80)μg.L-1]与非DKA组T3[(1.02±0.38)μg.L-1]、T4[(9.28±2.85)μg.L-1]比较,差异均有统计学意义(Pa<0.000 1)。中、重度DKA组与非DKA组T3比较,差异有统计学意义(Pa<0.000 1),轻、中、重度DKA组与非DKA组T4比较,差异均有统计学意义(Pa<0.000 4,0.000 1)。DKA组与非DKA组TSH比较,差异无统计学意义(P>0.05)。结论 T1DM患儿甲状腺激素检测的结果主要表现为T3降低,部分伴T4降低,其疾病的严重程度与甲状腺激素降低程度一致,T1DM并DKA患儿的T3、T4水平均有明显下降,提示T1DM患儿需重视甲状腺激素的检测,利于早期防治。     

Pittsburgh Diabetes Mellitus Study: Studies on the Etiology of Insulin-Dependent Diabetes Mellitus with Special Reference to Viral Infections

The etiology of IDDM remains incompletely understood, with genetic predisposition, autoimmune destruction of the beta cells and viral infections interacting to produce disease. It appear that the underlying genetic defect is an alteration in cellular and/or humorally-mediated immunological responsiveness. There are at least two (and probably more) genetically determined defects identified by HLA B-8 (DR3) and B- 15 (DR4). A number of viruses have been implicated in IDDM causation, including Coxsackie, mumps, rubella, Epstein-Barr, hepatitis and influenza viruses, but in only a few cases is viral etiology fully documented. Viral infections may trigger autoimmunity. Alterations in immunoglobulin concentration, particularly IgA deficiency, have been reported by several investigators. Collaborative prospective studies of individuals at high risk for the development of IDDM (siblings with HLA identical to the index case) are essential in the future study of IDDM etiology.     

Lipaemia Retinalis in Untreated Diabetes Mellitus

A 6-year-old girl developed diabetes mellitus, with marked hyperlipaemia and lipaemic retinalis, both of which rapidly cleared after insulin treatment. Biochemical studies led to the conclusion that dietary fat was the chief source of the excess triglyceride in the blood.     

儿童糖尿病流行病学研究现状

糖尿病(DM)是我国儿科领域的一种少见病,一直未能引起重视。随着社会发展、生活水平迅速提高和生活方式的改变,儿童和青少年DM,尤其是2型DM的发生率呈快速上升趋势,正在成为危害儿童和青少年健康的重要疾病,应引起儿科医师的关注。本文总结本病在国际、国内的流行病学研究现状。