When a child presents with acute febrile illness, maculopapular or erythematous rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and features suggestive of capillary leak, diagnosis of Scrub typhus must be considered and the child should be started on empirical therapy with doxycycline or azithromycin which is life saving.
Diabetic keto acidosis (DKA) is the major cause for mortality in children with Diabetes mellitus (DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries.Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians. Key words: Diabetic keto acidosis; Mortality; Cerebral edema; Sepsis; Shock; Delayed diagnosis Core tip: Mortality in Diabetic keto acidosis (DKA) among children from developed countries is due to cerebral edema and is very low. The mortality in DKA among children from developing countries is due to higher incidence of cerebral edema, sepsis, shock and renal failure. Delayed diagnosis is the root cause for high mortality in children with DKA from developed countries. There is an urgent need to increase the awareness about diabetes among the public and physicians.Poovazhagi V. Risk factors for mortality in children with diabetic keto acidosis from developing countries. World J Diabetes 2014; 5(6): 932-938 Available from:
Mutations in the pancreatic ATP sensitive K(+) channel proteins [sulfonyluea receptor 1 (SUR1) and inward rectifier K(+) channel Kir6.2 (Kir6.2), encoded by ATP-binding cassette transporter subfamily C member 8 (ABCC8) and potassium channel J11 (KCNJ11), respectively], are the most common cause of neonatal diabetes. We describe the clinical presentation and molecular characterization of Asian Indian children with neonatal diabetes mellitus and monogenic syndromes of diabetes. We sequenced KCNJ11, ABCC8 and insulin (INS) genes in 33 unrelated Indian probands with onset of diabetes below one year of age. A total of 12 mutations were identified which included ABCC8 mutations in seven, KCNJ11 mutations in three and INS mutations in two children. The Asp212Tyr mutation in ABCC8 was novel. We also detected two novel mutations (Val67Met and Leu19Arg) in children with syndromic forms of diabetes like Berardinelli Seip syndrome [1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)] and Fanconi Bickel syndrome [solute carrier family 2A2 (SLC2A2)]. Children carrying the KCNJ11 (Cys42Arg, Arg201Cys) and ABCC8 (Val86Ala, Asp212Tyr) mutations have been successfully switched over from insulin therapy to oral sulfonylurea. Our study is the first large genetic screening study of neonatal diabetes in India.
Background and Aims:Pediatric index of mortality (PIM) 2 score is one of the severity scoring systems being used for predicting outcome of patients admitted to intensive care units (ICUs). The aim of the present study was to evaluate the usefulness of PIM2 score in predicting mortality in a tertiary care pediatric ICU (PICU) and to assess the associated factors in predicting mortality such as presence of shock, need for assisted ventilation and Glasgow coma scale <8.Materials and Methods:This was a prospective observation study done at tertiary care PICU from May 2011 to July 2011. Consecutive 119 patients admitted to PICU (aged 1 month to 12 years) were enrolled in the study. PIM2 scoring was done for all patients. The outcome was recorded as death or discharge. The associated factors for mortality were analyzed with SPSS 17.Results:PIM2 score discriminated between death and survival at a 99.8 cut-off, with area under receiver operating characteristic curve 0.843 with 95% confidence interval (CI) (0.765, 0.903). Most patients were referred late to this hospital, which explains higher death rate (46.2%), lesser length of hospital stay (mean 2.98 days) in the mortality group, and increased rate of mechanical ventilation (68.1%). Presence of shock was independently associated with mortality, as evidenced by binary logistic regression.Conclusion:PIM2 score discriminated well between survivors and death at PICU. Presence of shock was significantly associated with mortality.
Aims/hypothesisThe pancreatic ATP-sensitive potassium (KATP) channel plays a pivotal role in linking beta cell metabolism to insulin secretion. Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively. To date, all patients affected by neonatal diabetes due to a mutation in the pore-forming subunit of the channel (Kir6.2, KCNJ11) are heterozygous for the mutation. Here, we report the first clinical case of neonatal diabetes caused by a homozygous KCNJ11 mutation.MethodsA male patient was diagnosed with diabetes shortly after birth. At 5 months of age, genetic testing revealed he carried a homozygous KCNJ11 mutation, G324R, (Kir6.2-G324R) and he was successfully transferred to sulfonylurea therapy (0.2 mg kg−1 day−1). Neither heterozygous parent was affected. Functional properties of wild-type, heterozygous and homozygous mutant KATP channels were examined after heterologous expression in Xenopus oocytes.ResultsFunctional studies indicated that the Kir6.2-G324R mutation reduces the channel ATP sensitivity but that the difference in ATP inhibition between homozygous and heterozygous channels is remarkably small. Nevertheless, the homozygous patient developed neonatal diabetes, whereas the heterozygous parents were, and remain, unaffected. Kir6.2-G324R channels were fully shut by the sulfonylurea tolbutamide, which explains why the patient’s diabetes was well controlled by sulfonylurea therapy.Conclusions/interpretationThe data demonstrate that tiny changes in KATP channel activity can alter beta cell electrical activity and insulin secretion sufficiently to cause diabetes. They also aid our understanding of how the Kir6.2-E23K variant predisposes to type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-3964-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
SummaryCongenital hyperinsulinemic hypoglycemia (HI) is a heterogeneous genetic disorder of insulin secretion characterized by persistent hypoglycemia, most commonly associated with inactivating mutations of the β-cell ATP-sensitive K + channel (K ATP channel) genes ABCC8 (encoding SUR1) and KCNJ11(encoding Kir6.2). This study aimed to screen the mutations in the genes associated with congenital HI in Asian Indian children. Recessive mutations of these genes cause hyperinsulinism that is unresponsive to treatment with channel agonists like diazoxide. Dominant K ATP mutations have been associated with diazoxide-responsive disease. The KCNJ11, ABCC8, GCK, HNF4A, and GLUD1 genes were analyzed by sequence analysis in 22 children with congenital HI. We found 10 novel mutations (c.1delA, c.61delG, c.267delT, c.619-629delCCCGAGGACCT, Gln444* , Leu724Pro, Ala847Thr, Trp898 * , IVS30-2A>C, and Leu1454Arg) and two known mutations (Gly111Arg and Arg598 * ) in the ABCC8 gene. This study describes novel and known ABCC8 gene mutations in children with congenital HI. This is the first large genetic screening study on HI in India and our results will help clinicians in providing optimal treatment for patients with hyperinsulinemia and in assisting affected families with genetic counseling.
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