高胰岛素血症高氨血症综合征诊治研究进展

高胰岛素血症-高氨血症综合征(hyperinsulinism-hyperammonemia syndrome,HI/HA syndrome)是先天性高胰岛素血症(HI)中第二大常见亚型.患有该综合征的儿童有空腹和高蛋白质饮食诱发的低血糖,并伴有持续高氨血症.编码谷氨酸脱氢酶的基因GLUD1致病变异是HI/HA综合征的病...     

100例新生儿血氨值测定

为探讨新生儿高氨血症(NHA)的原因及高氨血症对新生儿行为能力的影响,我们对100例新生儿进行了血氨值测定。对象和方法采用微量扩散法(日本试剂),对1985年10月至1986年3月生于佳木斯医学院100例出生72小时     

新生儿高胰岛素血症致顽固性低血糖三例

新生儿期反复、持续发作低血糖应考虑高胰岛素血症的可能,如诊断治疗不及时,可因低血糖及抽搐引起永久性脑损害及智力低下,甚至死亡,我院1985年以来收治3例介绍如下。     

新生儿先天性高胰岛素血症的治疗进展

先天性高胰岛素血症(congenital hyperinsulinism,CHI)是由于一组基因突变导致胰岛β细胞不规律释放胰岛素所致的一种高胰岛素低血糖综合症。CHI患者因为持续、反复发作的低血糖极易造成永久性脑损伤,正确及时的诊疗对预防癫痫、脑瘫及其他神经系统损伤等后遗症至关重要。目前研究表明相当一部分患者可以用药物控制,常用药物有二氮嗪、奥曲肽、胰高血糖素等。内科治疗无效时,外科治疗对局灶型CHI患者也有较好的疗效。本文就近年来CHI治疗研究进展进行综述。     

新生儿高胰岛素血症研究进展

先天性高胰岛素血症(congenital hyperinsulinism,CHI)在临床上可以表现为一种非常严重甚至是危及生命的疾病,尤其可导致新生儿生后持久性低血糖,所以近年来称之为“婴儿持续性高胰岛素血症”(persistent hyperinsulinemia hypoglycemia of infancy,PHHI)。低血糖可致永久性脑损伤、脑萎缩,也可能表现为很轻微甚至无症状。在临床上从发病年龄、疾病严重度及对药物治疗后的反应都有很大的差别。最近人们从分子病因学卜进行进一步研究,更清楚地阐明了这种临床表现的差异性,为高胰岛素血症(HI)的诊断和治疗提供厂很好的方法。     

母血与其新生儿脐血之间血糖及胰岛素水平比较

本文分别测定了母亲及其新生儿脐血的血糖及胰岛素。７９例正常新生儿（组１）及２６例巨大儿）组２）来自糖筛查或糖耐量试验正常的母亲，７例新生儿（组３）来自妊娠期糖尿病的母亲。所有新生儿脐血糖平均均值也明显低于其母血，差别有显著性（因分别为Ｐ〈０．００５，〈０．００１，〈０．０５）。组１和组２的新生儿脐血胰岛素平均值也明显低于其母血，差别有显著性（Ｐ〈０．００１，〈０．０２５）。３例新生儿发生低血糖，２     

高胰岛素血症伴高氨血症综合征1例报告并文献复习

目的探讨GLUD1基因变异所致高胰岛素血症伴高氨血症综合征临床表现和致病基因特点。方法回顾分析1例高胰岛素血症伴高氨血症综合征患儿的临床资料,并复习相关文献。结果女性患儿,1岁9个月起病,反复出现血糖偏低2年余,并惊厥发作3次,给予升血糖、止惊对症处理后可缓解;伴血胰岛素、血氨水平升高,诊断为高胰岛素血症伴高氨血症综合征。高通量测序发现患儿GLUD1基因存在错义变异c.965GA,p.Arg322His(杂合),其父母该位点均为正常基因型,为新生突变。结论基因检测有助于明确高胰岛素血症伴高氨血症综合征诊断。     

重视新生儿高氨血症

新生儿高氨血症病因复杂、进展迅速,如漏诊或血氨控制不及时,会导致患儿生命危险或预后不良。但由于新生儿高氨血症临床表现缺乏特异性,加之临床医师认识不足,常导致误诊或漏诊。现对新生儿高氨血症诊治中的临床问题进行总结和讨论,以引起临床医师的重视,提高诊疗水平,降低致残率及病死率。     

胰岛素样生长因子-1在新生儿高胆红素血症中的变化及意义

目的：胰岛素样生长因子-1(IGF-1)是神经系统必需的调节因子,目前少有报道其与高胆红素血症之间的关系。该文主要通过测定高胆红素血症（高胆）新生儿血清中IGF-1水平及新生儿神经行为评分(NBNA)来探讨IGF-1与高胆的关系及其临床意义。方法：应用电化学发光分析法检测57例高胆新生儿和 25例正常新生儿血清中IGF-1 浓度,同步测定血清总胆红素(TSB)、未结合胆红素(USB)及白蛋白(ALB)含量,计算USB与ALB比值(B/A),并行新生儿 NBNA 评分。高胆组按血清TSB值221~256 μmol/L,257~342 μmol/L,＞342 μmol/L分为轻、中、重三组;对照组TSB ＜85 μmol/L。结果：轻、中、重高胆患儿血清IGF-1浓度均值分别为39.38±8.42,30.77±4.65,26.34±2.05 ng/L,较对照组50.16±15.73 ng/ L明显降低,在轻、中、重高胆组间IGF-1浓度差异存在显著性(P＜0.01),其值随着胆红素的升高而降低;轻、中、重高胆组NBNA评分均值分别为35.01±2.26,32.45±2.74,26.77±5.02,明显低于对照组38.24±0.78(P＜0.01),高胆各组间差异也有显著性(P＜0.01);血清IGF-1 浓度与NBNA评分呈正相关(r=0.603, P＜0.01),与B/A值呈负相关(r=-0.483, P＜0.01)。结论：高胆患儿血清IGF-1浓度显著降低,降低程度与血清胆红素水平有关;IGF-1可能与新生儿胆红素脑损伤密切相关。［中国当代儿科杂志,2009,11（5）：357-360］     

Glucose metabolism in a term infant with transient hyperinsulinism and high carbohydrate intake

Transient hyperinsulinaemia is a well-known cause of hypoglycaemia in newborn infants. The hypoglycaemia may be caused by a decreased glucose production and/or an increased glucose uptake. Whether the increased uptake is caused by increased glucose oxidation or increased non-oxidative disposal is not known. The aim of this study was to investigate the fate of the large amount of glucose infused in a term infant who developed hypoglycaemia due to transient hyperinsulinaemia shortly after birth and was treated with high glucose infusions. On day 6 an indirect calorimetry study was performed, together with a glucose turnover study. Carbohydrate intake was 13.6 mg/kg per minute (19.6 g/kg per day). Both studies were repeated on day 11, when carbohydrate intake was normalised to 7.8 mg/kg per minute (11.2 g/kg per day). Glucose oxidation was 28% higher and non-oxidative glucose disposal was 257% higher on day 6 as compared to day 11. Our results indicate that hypoglycaemia during hyperinsulinism is the result of increased non-oxidative disposal of glucose and not increased glucose oxidation. The results indicate a remarkable capacity of the newborn for lipogenesis during high carbohydrate intake.     

Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism

OBJECTIVES: To characterize the clinical features and insulin regulation in infants with hypoglycemia due to prolonged neonatal hyperinsulinism. STUDY DESIGN: Data were collected on 26 infants with hypoglycemia due to neonatal hyperinsulinism that later resolved. Acute insulin response (AIR) tests to calcium, leucine, glucose, and tolbutamide were performed in 11 neonates. Results were compared to children with genetic hyperinsulinism due to mutations of the adenosine triphosphate-dependent potassium (K(ATP)) channel and glutamate dehydrogenase (GDH). RESULTS: Among the 26 neonates, there were significantly more males, small-for-gestational-age infants, and cesarean deliveries. Only 5 of the 26 had no identifiable risk factor. Hyperinsulinism was diagnosed at a median age of 13 days (range, 2 to 180 days) and resolved by a median age of 181 days (range, 18 to 403 days). Diazoxide was effective in 19 of the 21 neonates treated. In the 11 neonates tested, the AIRs to calcium, leucine, glucose, and tolbutamide resembled those in normal controls and differed from genetic hyperinsulinism due to K(ATP) channel and GDH mutations. CONCLUSIONS: We define a syndrome of prolonged neonatal hyperinsulinism that is responsive to diazoxide, persists for several months, and resolves spontaneously. AIR tests suggest that both the K(ATP) channel and GDH have normal function.     

Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome

OBJECTIVE: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is associated with gain of function mutations in the leucine-stimulated insulin secretion pathway, we examined whether protein feeding or fasting was responsible for hypoglycemia in affected patients. STUDY DESIGN: Patients with HI/HA (8 children and 6 adults) were studied. All had dominantly expressed mutations of glutamate dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The responses to a 24-hour fasting test were determined in 7 patients. Responses to a 1.5 gm/kg oral protein tolerance test in 12 patients were compared with responses of 5 control subjects. RESULTS: The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with HI/HA showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with HI/HA and control subjects. CONCLUSION: The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA syndrome.     

Reversible obstructive hypertrophic cardiomyopathy in the Beckwith-Wiedemann syndrome

Summary Patients with the Beckwith-Wiedemann (B-W) syndrome have been reported to have an increased risk of congenital heart disease and of idiopathic cardiomegaly on chest x-ray. In the infant described here, reversible obstructive hypertrophic cardiomyopathy was documented and its relationship to the metabolic features of the B-W syndrome is discussed.     

Central nervous system hyperexcitability associated with glutamate dehydrogenase gain of function mutations

OBJECTIVE: To describe seizure phenotypes associated with the hyperinsulinism/hyperammonemia syndrome (HI/HA), which is caused by gain of function mutations in the enzyme glutamate dehydrogenase (GDH). STUDY DESIGN: A retrospective review of records of 14 patients with HI/HA. RESULTS: Nine patients had seizures as the first symptom of HI/HA, and six had seizures in the absence of hypoglycemia. No electroencephalogram (EEG) background abnormalities were identified. In four patients, EEG recordings during seizures in the setting of normal blood glucose contained generalized epileptiform discharges. EEGs of three of these patients showed 0.5- to 2-second generalized irregular spike-and-wave discharge at 3 to 6 Hz corresponding to eye blinks, eye rolling, or staring. The EEG of the fourth patient consisted of 20 seconds of generalized regular spike-and-wave discharge at 3 Hz in the clinical context of staring and unresponsiveness. In two patients, seizure control worsened with carbamezapine or oxcarbezapine treatment. CONCLUSIONS: In patients with HI/HA, generalized seizures are common and can occur in the absence of hypoglycemia. The drugs carbamazepine and oxcarbazepine should be used with caution for treatment. Pathogenesis of epilepsy in these patients may be related to effects of GDH mutations in the brain, perhaps in combination with effects of recurrent hypoglycemia and chronic hyperammonemia.     

Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings

Pyruvate dehydrogenase (PDH) deficiency is one of the most common causes of congenital lactic acidosis. Correlations between the genetic defect and neuroimaging findings are lacking. We present conventional and diffusion-weighted MRI findings in a 7-day-old male neonate with PDH deficiency due to a mosaicism for the R302H mutation in the PDHA1 gene. Corpus callosum dysgenesis, widespread increased diffusion in the white matter, and bilateral subependymal cysts were the main features. Although confirmation of PDH deficiency depends on specialized biochemical analyses, neonatal MRI plays a role in evaluating the pattern and extent of brain damage, and potentially in early diagnosis and clinical decision making.     

Neonatal Bartter syndrome

A case of neonatal Bartter syndrome is reported. The baby born pre-term following a pregnancy complicated by polyhydramnios, presented at 7 months of age with failure to thrive, gastroenteritis and facial dysmorphisms. An unusual feature was the absence of the classical biochemical abnormality of hypochloremic alkalosis early in the course of the disease. Metabolic acidosis was the initial manifestation at 5 weeks of age. Awareness of this presentation is important to avoid delay in diagnosis and treatment.