Cases Of Neonatal Diabetes Mellitus Research Articles

What Do We Know about Neonatal Diabetes caused by PDX1 Mutations?

Neonatal diabetes mellitus (NDM) is characterized by severe hyperglycemia, usually diagnosed in the first few months of an individual's life. It is a genetic disease and one of the main forms of monogenic diabetes. Changes in different genes have already been associated with NDM, including changes in the gene PDX1. In this review, we intend to summarize all neonatal diabetes cases caused by PDX1 mutations reported in the literature. For this purpose, we searched keywords in the literature from PubMed and articles cited by the HGMD database. The search retrieved 84 articles, of which 41 had their full text accessed. After applying the study exclusion criteria, nine articles were included. Of those articles, we detected thirteen cases of NDM associated with changes in PDX1; the majority in homozygous or compound heterozygous patients. Until now, variants in the PDX1 gene have been a rare cause of NDM; however, few studies have included the screening of this gene in the investigation of neonatal diabetes. In this review, we reinforce the importance of the PDX1 gene inclusion in genetic NGS panels for molecular diagnosis of NDM, and systematic morphological and functional exams of the pancreas when NDM is present.

Genetic and clinical features of neonatal and early onset diabetes mellitus in a tertiary center cohort in Brazil.

Neonatal diabetes mellitus (NDM) is defined as the occurrence of severe hyperglycemia in infants under 6 months old and may be permanent (PNDM) or transient (TNDM). When diabetes is diagnosed at 6-12months of age (early onset diabetes [EOD]), the etiology may be monogenic; however, most cases consist of type 1 diabetes mellitus (T1DM). Molecular diagnosis was determined in a cohort of 35 unrelated Brazilian patients with NDM or EOD based on targeted next-generation sequencing panel and/or chromosome 6q24 abnormalities. The impact of genetic testing on treatment and follow-up was evaluated. Overall, 24 patients had NDM: with 18 (75.0%) having PNDM, 5 TNDM (20.8%) and 1 case in which this information was unknown. Eleven patients had EOD. Genetic testing was positive in 20/24 patients with NDM (83.3%) and in 18.2% of cases of EOD. The commonest causes were ATP-sensitive potassium (KATP) channel genes, and GCK and IPEX mutations (37.1%, 11.4% and 5.7%, respectively). Patients with PNDM due to KCNJ11 and ABCC8 mutations transitioned successfully to sulfonylureas in almost 60% of cases, reinforcing the benefit of performing genetic testing in NDM as early as possible. This report refers to the largest series of cases of NDM (TNDM and PNDM) and EOD in Brazil in which patients were submitted to molecular investigation and in which the clinical impact of genetic diagnosis was also evaluated.

Sochetanie saharnogo diabeta I tipa i diabeta, svyazannogo s mutaciej gena GCK

While the incidence of type 1 diabetes mellitus (Dm1) and type 2 diabetes mellitus (Dm2) in children increases due to the influence of various environmental factors, the frequency of new cases of monogenic diabetes, namely MODY (adult type diabetes in young people), increases due to the widespread introduction of modern diagnostic capabilities, including genetic research. As of 2021, 50 cases of neonatal diabetes mellitus (1 in 152.280) have been registered in Russia, for which a molecular genetic study has been conducted, however, the prevalence of GCK in Russia remains largely uncertain due to the lack of nationwide screening for diabetes-associated autoantibodies and limited access to molecular genetic testing.

Permanent Neonatal Diabetes Mellitus in an Indian Infant Due to a Novel Mutation in the Glucokinase Gene

Background: Neonatal diabetes mellitus (NDM) is a rare condition, usually genetic in etiology, that presents with hyperglycemia requiring insulin within the first 6 months of life. Most cases of permanent NDM are caused by mutations in the KCNJ11 or ABCC8 gene, which are involved in the potassium adenosine triphosphate channels. Clinical Description: A 1.88 kg female infant product of a consanguineous marriage was delivered at term by cesarean section for oligohydramnios and intrauterine growth retardation. There was a strong family history of DM involving the mother, father, and grandparents. Clinical examination was normal. Routine blood sugar monitoring identified hyperglycemia at 1 and 3 h. There was no clinical or laboratory evidence of sepsis. Management: Persistent hyperglycemia continued that necessitated the administration of insulin from the 1st day onward. The abdominal ultrasonogram was normal. C-peptide was low, indicating poor endogenous insulin production. Genetic analysis revealed a novel mutation in the glucokinase (GCK) gene (p. Glu178Asp). A brief trial of sulfonylureas (glibenclamide) was ineffective. The infant attained control, although with considerable difficulty, on a mixture of NPH and long-acting insulin. After 5 months of follow-up, she is thriving well. Conclusion: GCK mutation is a rare but important cause of NDM. To the best of our knowledge, this is the first Indian infant to be reported with a GCK gene mutation.

Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience

Background: Diabetes diagnosed within the first 6 months of life is defined as neonatal diabetes mellitus (NDM). Mutations in the KCNJ11, ABCC8, and INS genes are the most common cause of permanent NDM. In populations with a high rate of consanguinity, Wolcott-Rallison syndrome caused by biallelic EIF2AK3 mutations is common. Methods: We studied the clinical characteristics and underlying genetic cause of disease in 15 individuals with diabetes onset before 6 months of age as defined by sustained hyperglycaemia requiring insulin treatment. Patients who had a remission of the diabetes, defined by a normal blood glucose and HbA1c value without insulin or sulphonylurea (SU) treatment, within the first 18 months of life were classified as having transient NDM (TNDM). Results: We report 15 patients with NDM from 14 unrelated families, including 10 with reported parental consanguinity. 1/15 patients had a remission of diabetes, leading to a diagnosis of TNDM. Mutations were detected in 80% (n = 12/15) of the cohort (ABCC8 [n = 4], PTF1A-distal enhancer [n = 3], KCNJ11 [n = 2], EIF2AK3 [n = 1], INS [n = 1], and SLC19A2 [n = 1]). All cases were initially treated with multiple dose insulin injections. One patient with an ABCC8 mutation transitioned from insulin to SU resulting in improved metabolic control at the age of 20 years. Conclusion: Although the number of individuals born to consanguineous parents was considerably high in this cohort, KATP channel mutations (ABCC8/KCNJ11) were more common than EIF2AK3 mutations (n = 6 vs. n = 1). Genetic analyses should be performed in all NDM cases due to the potential impact on treatment and prognosis.

Clinical features and partial proportional molecular genetics in neonatal diabetes mellitus: a retrospective analysis in southwestern China.

To explore the relationship of phenotype and genotype of neonatal diabetes mellitus (NDM) in southwestern China. Sixteen cases of NDM admitted to Children's Hospital of Chongqing Medical University from May 2009 to May 2019 were included in this study. The clinical features of the included infants were retrospectively analyzed. Peripheral blood samples of the patients and their parents were collected for mutation detection. Among the 16 cases of NDM, 8 cases were permanent neonatal diabetes mellitus (PNDM) (including 3 clinical syndromes), and 3 cases were transient neonatal diabetes mellitus (TNDM). Mutation detection was performed in six cases. The mutation genes and their loci were FOXP3 p.V408M, KCNJ11 p.C166Y, ABCC8 p.S830P, KCNJ11 p.I182T, KCNJ11 p.G334D, and ZFP57 p.R125X,412. ABCC8 p.S830P was the new found pathogenic site of gene mutation. According to the clinical features and follow-up results, one case was diagnosed as IPEX syndrome, two as DEND syndrome, two as simple PNDM, and one as TNDM. All the TNDM could spontaneously alleviate and then insulin was withdrawn. In PNDM, 75% of those with KATP channel gene mutation could be completely or partially converted to oral sulfonylureas treatment, however, the rest cases needed lifelong insulin replacement therapy. The clinical manifestations and treatment regimens of patients with NDM vary according to the type of gene mutation. Even the same mutant genotype has differences in phenotype and response to treatment.

Association of NAD + ADP-ribosyltransferase 1 gene polymorphism with the development of neonatal diabetes mellitus

Regulation of glucose metabolism by NAD-dependent ADP-ribosyltransferase is well investigated in different populations. Genetic variations NAD + ADP-ribosyltransferase has been shown to alter the activity of the enzyme and associated with susceptibility to diabetes. However, reports on neonatal diabetes are minimal. We, therefore, in the present report aimed to investigate the involvement of NAD + ADP-ribosyltransferase variants as a possible risk factor for predisposition to neonatal diabetes mellitus in Chinese patients. Neonatal subjects diagnosed with diabetes mellitus and healthy infants from a similar geographical area were enrolled at China-Japan Union Hospital of Jilin University, China. The involvement of NAD + ADP-ribosyltransferase with neonatal diabetes mellitus was investigated in DNA samples of all participants by PCR methods. One hundred Twenty neonatal diabetes mellitus cases and a matched number of healthy neonates were enrolled in the present study. GG and G SNPs of NAD + ADP-ribosyltransferase were mainly involved in developing neonatal diabetes mellitus and the individuals with GA SNPs protect responsible for protecting from neonatal diabetes mellitus. Thus, NAD + ADP-ribosyltransferase involved in neonatal diabetes mellitus and risk of developing is approx. 2 times higher compared to healthy subjects. Our finding showed that polymorphism in NAD + ADP-ribosyltransferase gene is associated with the predisposition to neonatal diabetes mellitus in Chinese. The present study also suggested that NAD + ADP-ribosyltransferase is a promising target for the treatment of neonatal diabetes mellitus and an effective care of patients. Our study results encourage conducting further investigation in the multi-centric clinical genetic study including larger samples to assesses the role of NAD + ADP-ribosyltransferase polymorphism in neonatal diabetes mellitus.

Iranian neonatal diabetes mellitus due to mutation in PDX1 gene: a case report

BackgroundNeonatal diabetes mellitus with hyperglycemia during the first 6 months of life is a rare disorder that can occur in all races and societies.Case presentationIn this study, we introduced an Iranian (Persian) 65-day-old patient with neonatal diabetes mellitus with novel homozygous mutation in the pancreatic and duodenal homeobox 1, PDX1, gene, which is also known as IPF1 gene, located in exon 2. This case was a newborn boy born in Vali-Asr Hospital, Tehran; he was diagnosed as having hyperglycemia on 28th day. Genetic analysis detected a homozygous mutation on PDX1 gene on chromosome 13. It is a novel homozygous mutation in the PDX1 gene (NM_000209.3), p.Phe167Val. This mutation was confirmed by Sanger sequencing. There was no evidence of agenesis of the pancreas.ConclusionsWe reported a case of neonatal diabetes mellitus due to novel homozygous mutation in the PDX1 gene without exocrine pancreas manifestations.

Transient neonatal diabetes mellitus caused by a novel mutation in the ABCC8 gene

Neonatal diabetes mellitus is a rare monogenic form of diabetes that develops in the first 6 months of life. Neonatal diabetes mellitus is commonly divided in two groups as transient and permanent. Genetic and epigenetic anomalies of chromosome 6q24 locus are responsible for 70% of transient neonatal diabetes mellitus cases. Incidence of macroglossia, umbilical hernia, cardiac and renal anomalies is increased in transient neonatal diabetes mellitus patients. Mutations in the genes (ABCC8 and KCNJ11) encoding two protein subunits (SUR1 and Kir6.2) of ATP-sensitive potassium channels constitute the second common cause of transient neonatal diabetes mellitus. In this article, we present a case with homozygous missense mutation (DNA expression: c1456> T), which was found in the ABCC8 gene in a 3.5-month-old patient with no congenital anomalies, leading to transient neonatal diabetes mellitus.

Human Genetics of Obesity and Type 2 Diabetes Mellitus: Past, Present, and Future.

Type 2 diabetes mellitus (T2D) and obesity already represent 2 of the most prominent risk factors for cardiovascular disease, and are destined to increase in importance given the global changes in lifestyle. Ten years have passed since the first round of genome-wide association studies for T2D and obesity. During this decade, we have witnessed remarkable developments in human genetics. We have graduated from the despair of candidate gene-based studies that generated few consistently replicated genotype-phenotype associations, to the excitement of an exponential harvest of loci robustly associated with medical outcomes through ever larger genome-wide association study meta-analyses. As well as discovering hundreds of loci, genome-wide association studies have provided transformative insights into the genetic architecture of T2D and other complex traits, highlighting the extent of polygenicity and the tiny effect sizes of many common risk alleles. Genome-wide association studies have also provided a critical starting point for discovering new biology relevant to these traits. Expectations are high that these discoveries will foster development of more effective strategies for intervention, through optimization of precision medicine approaches. In this article, we review current knowledge and provide suggestions for the next steps in genetic research for T2D and obesity. We focus on four areas relevant to precision medicine: genetic architecture, pharmacogenetics and other gene-environment interactions, mechanistic inference, and drug development. As we describe, the genetic architecture of complex traits has major implications for the prospects of precision medicine, rendering some anticipated approaches decidedly unrealistic. We highlight obstacles to the translation of human genetic findings into mechanism inference but are optimistic that, as these are overcome, there is untapped potential for novel drugs and more effective strategies for treating and preventing T2D and obesity.

An Activating Mutation in STAT3 Results in Neonatal Diabetes Through Reduced Insulin Synthesis.

Neonatal diabetes mellitus (NDM) is a rare form of diabetes diagnosed within the first 6 months of life. Genetic studies have allowed the identification of several genes linked to the development of NDM; however, genetic causes for ∼20% of the cases remain to be clarified. Most cases of NDM involve isolated diabetes, but sometimes NDM appears in association with other pathological conditions, including autoimmune diseases. Recent reports have linked activating mutations in STAT3 with early-onset autoimmune disorders that include diabetes of autoimmune origin, but the functional impact of STAT3-activating mutations have not been characterized at the pancreatic β-cell level. By using whole-exome sequencing, we identified a novel missense mutation in the binding domain of the STAT3 protein in a patient with NDM. The functional analyses showed that the mutation results in an aberrant activation of STAT3, leading to deleterious downstream effects in pancreatic β-cells. The identified mutation leads to hyperinhibition of the transcription factor Isl-1 and, consequently, to a decrease in insulin expression. These findings represent the first functional indication of a direct link between an NDM-linked activating mutation in STAT3 and pancreatic β-cell dysfunction.

A Novel Approach to the Management of Neonatal Diabetes Using Sensor-Augmented Insulin Pump Therapy With Threshold Suspend Technology at Diagnosis.

Neonatal diabetes mellitus (NDM) is a rare genetic condition with an incidence of 1 in 100,000 (1) that presents before 1 year of age (2). There are two main clinical forms of NDM: permanent NDM (PNDM), which requires lifelong treatment with insulin, and transient NDM (TNDM), which may spontaneously remit and sometimes recurs in the second to third decade of life. In most cases, TNDM and PNDM cannot be distinguished clinically at the time of diagnosis, and genetic analysis needs to be performed. The genetic origin for >90% of TNDM cases has been established. In TNDM, 68% of the cases have abnormalities in an imprinted region on chromosome 6q24; 10% have KCNJ11 gene mutations; and 13% have an ABCC8 gene mutation (3). Multiple genes involved in pancreatic development, β-cell apoptosis, or dysfunction cause PNDM (4). The most common mutations are in the KATP channel genes KCNJ11 (30%) and ABCC8 (11%) or the insulin (INS) gene (13%) (3). Insulin is acutely required in most infants to establish metabolic control in NDM (5). Early initiation of sulfonylurea treatment is also recommended (6) as a treatment option in selected cases of NDM caused by ABCC8 and KCNJ11 mutations, and, in responsive cases, sulfonylurea therapy provides better long-term metabolic control (7,8) and could even improve neurodevelopmental outcomes (9). The MiniMed 530G (Medtronic, Inc., Northridge, CA) is a first-generation artificial pancreas system approved by the U.S. Food and Drug Administration (FDA) on 26 September 2013 for the management of diabetes in people ≥16 years of age. The system includes an external glucose sensor and insulin pump, transmitter, glucose meter, and therapy management software. Sensor signals are transmitted to the MiniMed 530G insulin pump and converted into glucose values every 5 minutes. Fingerstick blood glucose testing is still required for both …

A case of transient neonatal diabetes due to a novel mutation in ABCC8.

Neonatal diabetes mellitus (NDM), characterized by hyperglycemia and the need for insulin treatment within the first 6 mo of life, is a rare monogenic form of diabetes with an estimated incidence of 1 in 90,000 neonates (1). Approximately half of NDM cases are transient and resolve at a median age of 3 mo (transient NMD: TNDM), while the remaining cases develop into a permanent form of diabetes (permanent NDM: PNDM; MIM # 606176). Adult onset non-autoimmune diabetes occurs in a significant number of patients with TNDM (2). Most cases of TNDM (approximately 70%) are caused by abnormalities in chromosome 6q24, including paternal duplications, paternal uniparental isodisomy, and loss of methylation. In a few patients, activating mutations in the genes, which encode the two subunits of the β-cell ATP-sensitive potassium channel, i.e. ABCC8 and KCNJ11, have been reported to be associated with TNDM. Interestingly, recent studies have shown that familial analysis of TNMD with ABCC8 mutations revealed that their family members with adult onset non-autoimmune diabetes also have the same mutations (3). Here, we present a Japanese case with TNDM harboring a novel p.Glu350Asp mutation in ABCC8. Familial analysis revealed that his non-symptomatic sister and mother, other family members with adult-onset diabetes without neonatal episodes of hyperglycemia, also possessed the same mutation.

Neonatal diabetes mellitus: the effectiveness of therapy with sulfonylurea preparations depending on the type of mutation in the KCNJ11 gene

Neonatal diabetes mellitus (NDM) develops within the first 6 months of life. It occurs with a frequency of 1 cases per 300,000 - 500,000 newborn infants. Pathogenesis of NDM involves over 10 different genes. Of greatest clinical significance are mutations in KCNJII and ABCC8 genes responsible for the activity of ATP-dependent potassium channels and regulating their activation. It was shown that the intake of oral sulfonylurea (SU) preparations results in the closure of these channels and thereby stimulates the release of insulin from beta-cells. For this reason, SU therapy can be applied as an alternative to insulin injections. SU preparations ensure the efficacious control of metabolic processes and substitute insulin in the majority of the cases of transient and permanent NDM associated with mutations in KCNJII and ABCC8 genes. The original observations demonstrating the relationship between the type of mutation in the KCNJII gene and the dose of SU preparations are presented.

Overexpression of ZAC impairs glucose‐stimulated insulin translation and secretion in clonal pancreatic beta‐cells

ZAC (Zinc finger protein that regulates apoptosis and cell-cycle arrest) is a candidate gene for transient neonatal diabetes mellitus (TNDM). This condition involves severe insulin deficiency at birth that reverses over weeks or months but may relapse with diabetes recurring in later life. ZAC overexpression in transgenic mice has previously been shown to result in complex changes in both beta-cell mass and possibly function. The present study therefore aimed to examine the role of ZAC in beta-cell function in vitro, independent of the confounder of a reduced beta-cell mass at birth. Overexpression of ZAC was achieved through the tetracycline-regulatable system in the beta-cell line, INS-1. We found that ZAC overexpression exerted no significant effect on proliferation in this transformed cell line at any of the glucose concentrations examined. By contrast, glucose-stimulated insulin secretion was impaired through a mechanism downstream of cytosolic Ca(2+) increases. Furthermore, glucose-stimulated proinsulin biosynthesis was inhibited despite an increase in insulin transcript level. Finally, we found that glucose downregulated ZAC expression in both INS-1 cells and primary mouse islets. These results indicate that ZAC is a negative regulator of the acute stimulatory effects of glucose on beta-cells, and provide a possible explanation for both insulin deficiency in the neonate and the later relapse of diabetes in patients with transient neonatal diabetes mellitus cases.

Neonatal Diabetes Mellitus in China

To recognize the clinical characteristics and outcomes of neonatal diabetes mellitus (NDM), the authors retrospectively reviewed 1 NDM baby in their department and compared their data with 39 NDM cases reported in the available Chinese literature between January 1986 and December 2010. Most of the cases were located near the eastern and southern coasts of China, and clinical manifestation of 72.5% of the cases occurred in 4-week-old infants. Hyperglycemia and glycosuria findings were seen in all the patients and in 47.5% with intrauterine growth retardation. Moreover, 30.0% of the cases had polyuria, 52.5% had dehydration, and 47.5% had ketoacidosis. Cases with hyperglycemia, dehydration, and ketoacidosis recovered mostly. Ten NDM cases had persisted after 1 to 11 years of follow-up, 3 cases maintained normal blood sugar, and 7 cases had poor sugar control. NDM is a rare condition and early management includes fluid and insulin and later management depends on the transient or permanent nature of the condition.

Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live births

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000–1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000 and 1:260,000 live births. Aim of the present work was to ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for years 2005–2010. Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000–1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year.

Genetics and pathophysiology of neonatal diabetes mellitus.

Neonatal diabetes mellitus (NDM) is the term commonly used to describe diabetes with onset before 6 months-of-age. It occurs in approximately one out of every 100,000-300,000 live births. Although this term encompasses diabetes of any etiology, it is recognized that NDM diagnosed before 6 months-of-age is most often monogenic in nature. Clinically, NDM subgroups include transient (TNDM) and permanent NDM (PNDM), as well as syndromic cases of NDM. TNDM often develops within the first few weeks of life and remits by a few months of age. However, relapse occurs in 50% of cases, typically in adolescence or adulthood. TNDM is most frequently caused by abnormalities in the imprinted region of chromosome 6q24, leading to overexpression of paternally derived genes. Mutations in KCNJ11 and ABCC8, encoding the two subunits of the adenosine triphosphate-sensitive potassium channel on the β-cell membrane, can cause TNDM, but more often result in PNDM. NDM as a result of mutations in KCNJ11 and ABCC8 often responds to sulfonylureas, allowing transition from insulin therapy. Mutations in other genes important to β-cell function and regulation, and in the insulin gene itself, also cause NDM. In 40% of NDM cases, the genetic cause remains unknown. Correctly identifying monogenic NDM has important implications for appropriate treatment, expected disease course and associated conditions, and genetic testing for at-risk family members. Early recognition of monogenic NDM allows for the implementation of appropriate therapy, leading to improved outcomes and potential societal cost savings. (J Diabetes Invest, doi:10.1111/j.2040-1124.2011.00106.x, 2011).

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.

Transfer from Insulin to Sulfonylurea Treatment in a Chinese Patient with Permanent Neonatal Diabetes Mellitus due to a KCNJ11 R201H Mutation

Neonatal diabetes mellitus (NDM) is a rare and specific type of diabetes which is characterized by onset of hyperglycemia within the first 6 months of life. The reported incidence of NDM is 1:300 000–400 000 in newborns [1] [2]. It is clinically classified into two groups: transient neonatal diabetes mellitus (TNDM) and permanent neonatal diabetes mellitus (PNDM). TNDM usually spontaneously resolves within the first months of life, with possible recurrence in childhood or adolescent stage. It represents 50% to 60% of cases of NDM, and is often associated with an abnormality of the imprinted region of 6q24 [1] [3]. In contrast, PNDM needs a lifelong medication. It has been recognized that heterozygous activating mutation in the KCNJ11 gene which encodes the Kir6.2 subunits of the ATP sensitive K+ channel (KATP channel) is a major cause of PNDM [1] [3]. And cases have been reported in which a better glycemic control was obtained after initiation of oral sulfonylurea treatment compared to insulin therapy [4] [5]. Here we report the first Chinese case of PNDM with a KCNJ11 R201H mutation and the successful transition from insulin injections to oral sulfonylurea therapy.