Unusual case of neonatal diabetes mellitus due to congenital pancreas agenesis

Congenital absence of the pancreas is an extremely rare condition. We participated in the care of a patient with an unusual presentation of neonatal diabetes attributable to agenesis of the pancreas. Additional clinical features of the patient included cardiac septal defects, gall bladder agenesis and duodenal malrotation. Appropriate institution of insulin, exocrine pancreatic supplements and surgical repair of the cardiac and intestinal anomalies resulted in the infant's survival. Of the reported cases of congenital pancreas agenesis, two cases have been ascribed to mutations in the insulin promoter factor-1(Ipf-1) gene. Deletion of the Ipf-1-homolog pdx-1 in mice results in the failure of pancreas to develop. Analysis of both exons of the Ipf-1 coding sequence from the presented patient's genomic DNA, however, did not identify a mutation. These results suggest that a congenital or genetic perturbation occurred in this infant most likely before the appearance of dorsal pancreatic bud in the 3 mm long embryonic stage, around the embryonic day 25 in human development, before the onset of Ipf-1 expression.     

新生儿糖尿病研究进展

新生儿糖尿病是一组异质性单基因遗传病,常被误诊为1型糖尿病.永久性新生儿糖尿病与免疫无关,主要与KCNJ 11、ABCC8和胰岛素基因等基因突变有关;多以酮症酸中毒起病,伴宫内发育迟缓、脱水.基因检测有助于疾病分型,并可根据不同致病基因进行靶向治疗.对于ATP敏感的K+通道基因突变的永久性新生儿糖尿病患儿可口服磺脲类降...     

新生儿糖尿病研究进展

大部分新生儿糖尿病(NDM)发柄与基因突变有关,部分NDM应用磺脲类药物治疗可取得良好疗效。新近研究从分子水平上阐明了NDM的发病机制及磺脲类药物的作用机制。另有研究表明糖化白蛋白是反映NDM血糖控制的有用指标。文章综述近年对NDM研究的进展。     

新生儿糖尿病的诊治思路

新生儿糖尿病（neonatal diabetes mellitus，NDM）是一种罕见的单基因病，临床表现隐匿，临床表型与基因型异质性大，容易延误诊断。近年来，随着基因检测技术的发展，越来越多的致病基因逐渐被认识，目前已知的有30多种基因变异可引起NDM，不同亚型的NDM在临床表现、治疗和转归等方面有所不同。染色体6q24印记区域的基因变异或甲基化异常是暂时性新生儿糖尿病（transient neonatal diabetes mellitus，TNDM）最常见的原因，ATP敏感性钾通道(K_ATP)基因（KCNJ11、ABCC8）变异是持续性新生儿糖尿病（persistent neonatal diabetes mellitus，PNDM）的最常见原因。NDM常需胰岛素替代治疗，而大约90%的KCNJ11或ABCC8变异的NDM患儿口服磺脲类药物治疗可维持稳定血糖水平，早期治疗还可逆转部分KCNJ11变异导致的神经发育迟缓，同时可增加从胰岛素转换至磺脲类药物治疗的成功率。早期明确遗传学诊断和分型有助于实现精准个体化治疗，判断预后。本文就NDM的基因型-临床表型及治...     

KCNJ11 activating mutations cause both transient and permanent neonatal diabetes mellitus in Cypriot patients

Heterozygous mutations of the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive potassium channel (K(ATP) channel) of the pancreatic β-cell cause diabetes in about 30-60% of all permanent neonatal diabetes mellitus cases diagnosed before 6 months of age. The K(ATP) channel plays an essential role in the regulation of the electrical status of the membrane through which the secretion of insulin is activated. Transient neonatal diabetes mellitus due to KCNJ11 mutations is less frequent than abnormalities affecting the imprinted region of chromosome 6q24. We studied the genetic basis of two Cypriot patients who developed diabetes before 6 months of age. They both carried mutations of the KCNJ11 gene. The R201H mutation was identified in a patient who developed hyperglycemia and ketoacidosis at the age of 40 d and was successfully transferred to sulphonylureas which activate the channel through an ATP independent route. The R50Q mutation was identified in a child diagnosed at day 45 after birth with remission of his diabetes at 9 months of age. The same defect was identified both in his asymptomatic mother and the recently diagnosed 'type 2' diabetic maternal grandmother. The remission-relapse mechanism in cases of transient neonatal diabetes is not known. Nevertheless, it is possible that the residue of the mutation within the Kir6.2 molecule is associated with the sensitivity to ATP reflecting to the severity of the diabetic phenotype.     

新生儿暂时性糖尿病1例

1　临床资料　　患儿 ,女 ,2ｄ ,因生后拒奶 4 4ｈ ,发热、阵发性四肢抽动 6ｈ入院。第 1胎 1产 ,孕 39周在家自然分娩 (新法接生 ) ,出生体重 190 0ｇ ,羊水呈深绿色 ,出生时全身青紫、不哭、呼吸弱 ,5ｍｉｎ后渐缓解 ,但一直很少哭、肢体活动少 ,出生后一直未吃奶或糖水 ,6ｈ前出现发热伴不规则阵发性四肢抽动。母孕期体健 ,饮食正常 ,无发热等疾病史 ,无毒物、药物、放射线接触史 ,无糖尿病家族史。查体 :Ｔ 37.7℃ ,Ｒ 6 6次 /ｍｉｎ ,Ｐ 16 8次 /ｍｉｎ ,体重 180 0 ｇ ,足月新生儿貌 ,发育营养较差 ,反应差 ,嗜睡 ,哭声弱 ,皮肤胎粪污…     

The genetic basis of neonatal diabetes mellitus

Neonatal diabetes mellitus is a rare condition occurring within the first few months of life that can either be permanent or transient. Various genetic defects responsible for both permanent and transient neonatal diabetes have been identified. ATP-sensitive potassium (KATP) channels are key regulators of nutrient-induced insulin secretion in pancreatic beta cells. Activating mutations of the KATP channel, which prevent closure of the channel and thus inhibit insulin secretion, are now known to be the predominant cause of permanent neonatal diabetes. Transient neonatal diabetes may also be associated with activating mutations of the KATP channel. However, the majority of cases of transient neonatal diabetes have a mutation that maps to a locus on the long arm of chromosome 6, and mutations in two overlapping genes, ZAC and HYMA1, have been identified as the predominant cause of transient neonatal diabetes. These findings provide important insights into the molecular and genetic basis in the broad spectrum of diabetes mellitus.     

A case of transient neonatal diabetes mellitus

We present a case of an 8-day-old infant boy with transient neonatal diabetes mellitus who presented to our emergency department with profound dehydration, failure to thrive, and hyperglycemia. The initial ill appearance of the patient required attention to a broad differential diagnosis including cardiac, metabolic, endocrine, and infectious processes. Transient neonatal diabetes mellitus is one of several causes of severe hyperglycemia in the neonatal period and is caused by genetic imprinting at the 6q24 region. It requires specific genetic testing for diagnosis. This case illustrates initial management of and recommended laboratory testing in neonates presenting with possible transient neonatal diabetes mellitus.     

Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia

Permanent neonatal diabetes mellitus (PNDM) is diagnosed within the first 6 months of life, and is usually monogenic in origin. Heterozygous mutations in ABCC8, KCNJ11, and INS genes account for around half of cases of PNDM; mutations in 10 further genes account for a further 10%, and the remaining 40% of cases are currently without a molecular genetic diagnosis. Thiamine-responsive megaloblastic anaemia (TRMA), due to mutations in the thiamine transporter SLC19A2, is associated with the classical clinical triad of diabetes, deafness, and megaloblastic anaemia. Diabetes in this condition is well described in infancy but has only very rarely been reported in association with neonatal diabetes. We used a combination of homozygosity mapping and evaluation of clinical information to identify cases of TRMA from our cohort of patients with PNDM. Homozygous mutations in SLC19A2 were identified in three cases in which diabetes presented in the first 6 months of life, and a further two cases in which diabetes presented between 6 and 12 months of age. We noted the presence of a significant neurological disorder in four of the five cases in our series, prompting us to examine the incidence of these and other non-classical clinical features in TRMA. From 30 cases reported in the literature, we found significant neurological deficit (stroke, focal, or generalized epilepsy) in 27%, visual system disturbance in 43%, and cardiac abnormalities in 27% of cases. TRMA should be considered in the differential diagnosis of diabetes presenting in the neonatal period.     

Continuous subcutaneous insulin infusion in neonatal diabetes mellitus

Abstract:  A 1.2-kg premature baby boy with severe intrauterine growth retardation developed diabetes on d 2 of life. The computed tomography scan of the pancreas failed to show the tail, indicating agenesis of the dorsal anlage. Continuous subcutaneous insulin infusion (CSII) had been used for the subsequent 26 months. Complications, such as hypoglycemia, were minimal.     

Transient neonatal diabetes mellitus: a patient report

A female newborn with transient neonatal diabetes mellitus is presented. No apparent genetic anomaly was detected, and the diabetes mellitus resolved by day 47 of life.     

Transient neonatal diabetes mellitus in extremely preterm infant

A report of transient neonatal diabetes mellitus in an extremely preterm infant (gestational age 27 weeks, birth weight 718 g). The patient had intrauterine growth retardation and developed hyperglycaemia on the first day of life. Insulin administration was discontinued on the 89th day of life, which was 1 day before the original due date. This case suggests that (a) insufficient insulin secretion started at least from the second trimester of the pregnancy; (b) the duration needed for recovery of insulin secretion was not dependent on the maturity.     

Glucose-monitoring with continuous subcutaneous microdialysis in neonatal diabetes mellitus

BACKGROUND: Neonatal diabetes mellitus can be extremely brittle. In this situation close glucose monitoring is essential for adequate insulin treatment. Continuous subcutaneous microdialysis is a promising approach for the babies to reduce the painful stress caused by diagnostic blood sampling. The goal of this study was to evaluate the feasibility of continuous subcutaneous microdialysis for glucose monitoring in a baby with neonatal diabetes and to assess the correlation between the blood and the subcutaneous glucose profile. PATIENT AND METHOD: During a period of seven days glucose monitoring was performed on a six month old infant with neonatal diabetes mellitus. In addition to frequent capillary blood glucose determinations, a continuous subcutaneous microdialysis device was used for the detection of the subcutaneous interstitial glucose concentration. RESULTS: Subcutaneous tissue glucose concentrations were measured in a wide range from 1.7 to 23.8 mM. Variations in the adipose tissue glucose concentration closely paralleled changes in the capillary blood glucose. Based on 104 reference pairs there was a high overall correlation (r = 0.89) between the subcutaneous interstitial tissue (X) and the blood (Y) glucose concentration (Y = 1.1 X + 0.29). However the glucose profiles demonstrated a considerable variation of the time lag, up to one hour, between blood and subcutaneous interstitial glucose concentration. CONCLUSIONS: Continuous subcutaneous microdialysis helps the glucose monitoring of infants with diabetes mellitus by providing additional informations about the rise and fall of the glucose concentration. Further studies should focus on how to get a tighter link between blood glucose and the subcutaneous interstitial glucose concentration in the area around the microdialysis probe. Thus monitoring the subcutaneous interstitial glucose concentration will become a reliable procedure for real-time glucose monitoring.     

Transient neonatal diabetes mellitus in a pair of twins

The occurrence of transient neonatal diabetes mellitus in male twins with almost identical courses of illness is reported. A trial with chlorpropamide treatment of twin A had no obvious influence on the insulin consumption or on duration of treatment. Very low values of plasma C-peptide and serum proinsulin with no detectable insulin antibodies supports the theory of delayed maturation of the beta-cell.     

Transitory neonatal diabetes mellitus and pericentric chromosome 9 inversion

Neonatal diabetes mellitus is an infrequent carbohydrate metabolism disorder with an estimated incidence of approximately one case every 400,000 to 600,000 live newborns. We present the case of a 1-month-old girl with irritability, polyuria, and a 24-h history of eagerness to feed, without fever or other associated symptoms. The patient's karyotype, obtained by amniocentesis, was 46XX with a pericentric chromosome 9 inversion. Her birth weight and length were 2,230 g (-2.65 SD) and 46 cm (-1.8 SD), respectively. Glycemic determinations during the first 72 h of extrauterine life oscillated between 90 and 157 mg/dl. Physical examination revealed general involvement, skin and mucosal pallor, evident signs of dehydration, and impaired awareness. Laboratory tests revealed glycemia: 1552 mg/dL, pH 7.16, pCO2: 23.7 mmHg; bicarbonate: 8.1 mEq/L, base excess: -19.1, and positive ketonemia. After initial stabilization, the patient was treated with intravenous fluids and continuous intravenous regular insulin infusion (initial dose 0.03-0.05 IU/kg/h). After intensive treatment, breast feeding was restored and a short-acting insulin analog was administered subcutaneously after every feed (0.1 to 0.3 IU according to capillary glycemic determinations). Insulin requirements decreased and were discontinued when the infant was 5 months old. Currently, the patient is 2 years and 7 months old and her glycemia and glycosylated hemoglobin levels are normal. Anti-islet (ICA and GAD) and anti-tyrosin phosphatase (IA2) antibodies were absent, as were mutations in the glucokinase gene (GCK).