Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neonatal diabetes mellitus is a rare (1/400 000 newborns) but potentially devastating condition, which may be transient or permanent; typical symptoms occur within the first 4 wk of life. The transient form is a developmental insulin production disorder that resolves postnatally. Fifty to 60% of cases can be seen as transient form. Cases that require lifelong insulin therapy can be described as permanent condition. This fraction of cases is less common than the transient form. There are no clinical features that can predict whether a neonate with diabetes mellitus but no other dysmorphology will eventually have permanent neonatal diabetes mellitus (PNDM) or transient neonatal diabetes mellitus. Some metabolic or genetic defects such as complete deficiency of glucokinase or heterozygous activating mutations of KCNJ11, encoding Kir6.2, were found in patients with PNDM. A preterm female infant with a gestational age of 36 wk was admitted to the neonatal intensive care unit in the first hours of life due to prematurity and intra-uterine growth retardation. She was diagnosed as having arthrogryposis multiplex congenita on the first day. Hyperglycemia was detected on the third day of life, and she required insulin treatment. The patient is now 6 yr old with PNDM, arthrogryposis multiplex, neurogenic bladder, immune deficiency, constipation, and ichthyosis. Is this a new form of neonatal diabetes mellitus?
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PMID:Permanent neonatal diabetes with arthrogryposis multiplex congenita and neurogenic bladder - a new syndrome? 1705 50

Hypoglycemia in infants and children can lead to seizures, developmental delay, and permanent brain damage. Hyperinsulinism (HI) is the most common cause of both transient and permanent disorders of hypoglycemia. HI is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia. The various forms of HI represent a group of clinically, genetically, and morphologically heterogeneous disorders. Congenital hyperinsulinism is associated with mutations of SUR-1 and Kir6.2, glucokinase, glutamate dehydrogenase, short-chain 3-hydroxyacyl-CoA dehydrogenase, and ectopic expression on beta-cell plasma membrane of SLC16A1. Hyperinsulinism can be associated with perinatal stress such as birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation, resulting in prolonged neonatal hypoglycemia. Mimickers of hyperinsulinism include neonatal panhypopituitarism, drug-induced hypoglycemia, insulinoma, antiinsulin and insulin-receptor stimulating antibodies, Beckwith-Wiedemann Syndrome, and congenital disorders of glycosylation. Laboratory testing for hyperinsulinism may include quantification of blood glucose, plasma insulin, plasma beta-hydroxybutyrate, plasma fatty acids, plasma ammonia, plasma acylcarnitine profile, and urine organic acids. Genetic testing is available through commercial laboratories for genes known to be associated with hyperinsulinism. Acute insulin response (AIR) tests are useful in phenotypic characterization. Imaging and histologic tools are also available for diagnosing and classifying hyperinsulinism. The goal of treatment in infants with hyperinsulinism is to prevent brain damage from hypoglycemia by maintaining plasma glucose levels above 700 mg/L (70 mg/dL) through pharmacologic or surgical therapy. The management of hyperinsulinism requires a multidisciplinary approach that includes pediatric endocrinologists, radiologists, surgeons, and pathologists who are trained in diagnosing, identifying, and treating hyperinsulinism.
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PMID:[Hyperinsulinism in infancy and childhood: when an insulin level is not always enough]. 1815 85

The most common monogenic cause of neonatal diabetes is mutation in KCNJ11, which encodes a potassium channel in pancreatic beta cells. Some mutations in this gene, including Q52R, have been described in association with neurological deficits, but never with hepatic involvement. We report the second case of neonatal diabetes in a patient with a KCNJ11/Q52R mutation. This patient's clinical course did not include obvious neurological deficits despite the presence of prematurity, but did include transient hyperbilirubinemia, and recurrent hypoglycemia. The phenotypic spectrum of KCNJ11 mutations is variable and is likely influenced by additional genetic and environmental factors.
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PMID:Permanent Neonatal Diabetes in a Patient with a KCNJ11/Q52R Mutation Accompanied by Intermittent Hypoglycemia and Liver Failure. 1995 3

Permanent neonatal diabetes mellitus (PNDM) is a rare form of diabetes diagnosed within the first 6 months of life. Heterozygous activation mutations in KCNJ11, encoding the Kir6.2 subunit of the ATP-sensitive potassium (K(ATP)) channel, which acts as a key role in insulin secretion regulation, account for about half of the cases of PNDM. The majority of the patients represent isolated cases resulting from de novo mutations. Approximately 20% have associated neurologic features: the most severe form, which includes epilepsy and developmental delay, is called developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome and the milder form, with less severe developmental delay and without epilepsy, is designated intermediate DEND syndrome. Individuals with KCNJ11 mutations have been successfully transitioned from insulin to sulfonylurea (SU) therapy. Furthermore, there have been cases reported with variable improvement in neurological function following a successful switching. We describe a 12-year-old Portuguese girl with PNDM due to the previously reported R201C mutation in the KCNJ11 gene. Her medical history includes prematurity and moderate developmental delay. The mutation was inherited from her mother who has isolated PNDM. The patient was successfully transferred from insulin to SU, whereas her mother showed SU resistance. Despite good glycemic control, no improvements in the cognitive performance were verified. We present our experience in switching treatment from insulin to oral SUs in this family, and also discuss whether or not the girl's developmental delay is related with the Kir6.2 mutation. To our knowledge, this is the first Portuguese patient reported with successful transition to SU treatment.
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PMID:Permanent neonatal diabetes mellitus due to KCNJ11 mutation in a Portuguese family: transition from insulin to oral sulfonylureas. 2276 71

First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide) is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1)-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel) and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis-all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options.
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PMID:Glibenclamide for the treatment of acute CNS injury. 2427 50