diabetestalk.net

Familial Hyperinsulinism Genereviews

International Journal Of Endocrinology And Metabolism

International Journal Of Endocrinology And Metabolism

International Journal of Endocrinology and Metabolism 1 Department of Pediatric Endocrinology, Mofid Childrens Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran 2 Genetic Counseling Division, Mofid Childrens Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran 3 Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, IR Iran 4 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran * Corresponding author: Susan Akbaroghli, Mofid Childrens Hospital, Tehran, IR Iran. Tel: +98-2122227033, Fax: +98-2122227033, E-mail: [email protected] International Journal of Endocrinology and Metabolism: October 2016, 14 (4) ; e37311.Published Online: September 10, 2016 Article Type: Case Report; Received : March 28, 2016; Revised : August 22, 2016; Accepted : September 5, 2016 DOI: To Cite : Alaei M R, Akbaroghli S, Keramatipour M, Alaei A. A Case Series: Congenital Hyperinsulinism, Int J Endocrinol Metab. 2016 ;14(4):e37311. doi: 10.5812/ijem.37311 . Introduction: Congenital hyperinsulinism is a rare inherited disease caused by mutations in genes responsible for -cells function in glucose hemostasis leading to profound and recurrent hypoglycemia. The incidence of the disease is about 1 in 50000 newborns. Mutations in at least 8 genes have been reported to cause congenital hyperinsulinism. Mutations in ABCC8 gene are the most common cause of the disease that account for approximately 40% of cases. Less frequently KCNJ11 gene mutations are responsible for the disease. Mutations in other genes such as HADH account for smaller fractions of cases. In nearly half of the cases the cause remains unknown. Case Presentation: During the period between 2005 and 2010, a total Continue reading >>

Approach To Hypoglycemia In Infants And Children

Approach To Hypoglycemia In Infants And Children

Approach to hypoglycemia in infants and children Approach to hypoglycemia in infants and children Approach to hypoglycemia in infants and children Correspondence to: Kajal Gandhi, DO, MPH. Section of Endocrinology, Nationwide Childrens Hospital, 700 Childrens Drive, Columbus, OH 43205, USA. Email: Abstract: Hypoglycemia is a heterogeneous disorder with many different possible etiologies, including hyperinsulinism, glycogen storage disorders, fatty acid disorders, hormonal deficiencies, and metabolic defects, among others. This condition affects newborns to adolescents, with various approaches to diagnosis and management. This paper will review current literature on the history of hypoglycemia, current discussion on the definition of hypoglycemia, as well as etiologies, diagnosis, and management. Keywords: Endocrinology; hypoglycemia; children Submitted Sep 25, 2017. Accepted for publication Oct 10, 2017. Hypoglycemia may be caused by various defective pathways in the production and metabolism of glucose, as well as defective pathways to maintain euglycemia. This review will discuss pertinent literature as it relates to the normal pathways for glucose utilization, history of hypoglycemia, select etiologies and approach to management. Throughout gestation, increasing glucose requirements by the growing fetus lead to transport of glucose through the placenta. This is performed by facilitated diffusion as the primary source of energy through the family of glucose transporter proteins (GLUT), primarily glucose transporter type 1 (GLUT1) through a concentration gradient which favors the fetus ( 1 - 3 ). Fetal glucose is mostly provided by maternal glucose supply ( 1 , 4 - 6 ), while fetal insulin functions primarily for growth ( 7 ). Although uterine glucose uptake is regula Continue reading >>

Arup Genetics Test Menu

Arup Genetics Test Menu

The test menu below is a complete list of ARUPs inherited disease testing. A patient history form is requested for many of these genetic tests. Click on the test code or test name to obtain a link to the patient history form for the desired test. DYPD 5-Fluorouracil toxicity5-FU toxicity5-FU toxicity5FU toxicityAdrucil (DPYD) Genotyping, 3 MutationsXeloda (capecitabine) (DPYD) Genotyping, 3 Mutations DPDUftoral (tegafur/uracil) (DPYD) Genotyping, 3 Mutations Acylcarnitine Quantitative Profile, Plasma ACYLCARN3-Hydroxy-3-Methylglutaryl-Coenzyme A Lyase Deficiency3-Hydroxy-3-Methylglutaryl-CoA Lyase DeficiencyHMG-CoA Lyase DeficiencyHMGCLHydroxymethylglutaryl-CoA lyase, mitochondrialHMG Lyase Deficiency3-Hydroxyacyl-Coenzyme A Dehydrogenase DeficiencyHADH DeficiencyHADHHydroxyacyl-coenzyme A dehydrogenase, mitochondrialSCHAD3-Methylglutaconic Aciduria Type 13-Methylglutaconyl-CoA Hydratase DeficiencyAUHMethylglutaconyl-CoA hydratase, mitochondrialMGA1MGA 1Acyl-CoA Dehydrogenase, Short/Branched Chain Deficiency2-Methyl Butyryl CoA Dehydrogenase DeficiencyAcyl-CoA Dehydrogenase, Short/Branched Chain DeficiencyACADSBShort/branched chain specific acyl-CoA dehydrogenase, mitochondrialSCADCarnitine Palmitoyltransferase IA DeficiencyCPT1A DeficiencyHepatic Carnitine Palmitoyltransferase 1 DeficiencyHepatic CPT1L-CPT 1 DeficiencyCPT1ACarnitine O-palmitoyltransferase 1, liver isoformCPT 1CPT 1ACPTICPT ICarnitine Palmitoyltransferase II DeficiencyCPT II DeficiencyCPT2Carnitine O-palmitoyltransferase 2, mitochondrialCPTIICPT 2Carnitine-Acylcarnitine Translocase DeficiencyCACT DeficiencySLC25A20Mitochondrial carnitine/acylcarnitine carrier proteinEthylmalonic EncephalopathyProtein ETHE1, mitochondrialETHE1EMAEthyl malonic acidEthylmalonic acidGA1Glutaricacidemia Type 1GAIGlutaricaci Continue reading >>

Hyperinsulinemic Hypoglycemia, Familial, 2

Hyperinsulinemic Hypoglycemia, Familial, 2

for Hyperinsulinemic Hypoglycemia, Familial, 2 UniProtKB/Swiss-Prot : 71 Familial hyperinsulinemic hypoglycemia 2: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. MalaCards based summary :Hyperinsulinemic Hypoglycemia, Familial, 2, also known as nesidioblastosis, is related to hypoglycemia and hyperinsulinemic hypoglycemia , and has symptoms including seizures, vomiting and diarrhea. An important gene associated with Hyperinsulinemic Hypoglycemia, Familial, 2 is KCNJ11 (Potassium Voltage-Gated Channel Subfamily J Member 11), and among its related pathways/superpathways are Integration of energy metabolism and Type II diabetes mellitus . Affiliated tissues include brain and pancreatic islet, and related phenotypes are endocrine/exocrine gland and homeostasis/metabolism Wikipedia : 72 Nesidioblastosis is a controversial medical term for hyperinsulinemic hypoglycemia attributed to... more... Continue reading >>

Congenital Hyperinsulinism: Current Trends In Diagnosis And Therapy

Congenital Hyperinsulinism: Current Trends In Diagnosis And Therapy

Orphanet Journal of Rare Diseases20116:63 Arnoux et al; licensee BioMed Central Ltd.2011 Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic -cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and gl Continue reading >>

Familial Hyperinsulinism.

Familial Hyperinsulinism.

Glaser B(1).In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews [Internet]. Seattle (WA): University of Washington,Seattle; 1993-2018.2003 Aug 19. (1)Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, Jerusalem, Israel CLINICAL CHARACTERISTICS: Familial hyperinsulinism (referred to as FHI in thisGeneReview) is characterized by hypoglycemia that ranges from severeneonatal-onset, difficult-to-manage disease to childhood-onset disease with mild symptoms and difficult-to-diagnose hypoglycemia. Neonatal-onset disease manifestswithin hours to two days after birth. Childhood-onset disease manifests duringthe first months or years of life. In the newborn period, presenting symptoms maybe nonspecific, including seizures, hypotonia, poor feeding, and apnea. In severecases, serum glucose concentrations are typically extremely low and thus easilyrecognized, whereas in milder cases, variable and mild hypoglycemia may make the diagnosis more difficult. Even within the same family, disease manifestations canrange from mild to severe. Individuals with autosomal recessive familialhyperinsulinism, caused by pathogenic variants in either ABCC8 or KCNJ11(FHI-KATP), tend to be large for gestational age and usually present with severe refractory hypoglycemia in the first 48 hours of life; affected infants usuallyrespond only partially to diet or medical management (i.e., diazoxide therapy)and thus may require pancreatic resection. Individuals with autosomal dominantFHI-KATP tend to be appropriate for gestational age at birth, to present atapproximately age one year (range: 2 days - 30 years), and to respond to diet anddiazoxide therapy. Exceptions to both of these generalities have been reported.FHI-GCK, caused by patho Continue reading >>

Omim Entry - # 256450 - Hyperinsulinemic Hypoglycemia, Familial, 1; Hhf1

Omim Entry - # 256450 - Hyperinsulinemic Hypoglycemia, Familial, 1; Hhf1

A number sign (#) is used with this entry because of evidence that familial hyperinsulinemic hypoglycemia-1 (HHF1) is caused by homozygous or compound heterozygous mutation in the ABCC8 gene (600509), encoding the SUR1 subunit of the pancreatic beta cell inwardly rectifying potassium channel, on chromosome 11p15. Familial hyperinsulinism, also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998). Genetic Heterogeneity of Hyperinsulinemic Hypoglycemia HHF2 (601820) is caused by mutation in the KCNJ11 gene (600937), on chromosome 11p15.1. HHF3 (602485) is caused by mutation in the glucokinase gene (GCK; 138079) on chromosome 7p15-p13. HHF4 (609975) is caused by mutation in the HADH gene (601609) on chromosome 4q22-q26. HHF5 (609968) is caused by mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13.2. HHF6 (606762) is caused by mutation in the GLUD1 gene (138130) on chromosome 10q23.3. HHF7 (610021) is caused by mutation in the SLC16A1 (600682) on chromosome 1p13.2-p12. There is evidence of further genetic heterogeneity of HHF. The term nesidioblastosis (meaning neoformation of islets of Langerhans from pancreatic duct epithelium) was coined by Laidlaw (1938) to describe the diffuse abnormality of the pancreas in which there is extensive, often disorganized formation of new islets. 'Nesidio' comes from a Greek word for islet. Yakovac et al. (1971) was first to report nesidioblastosis i Continue reading >>

Congenital Hyperinsulinism Sequencing Panel - Preventiongenetics

Congenital Hyperinsulinism Sequencing Panel - Preventiongenetics

Congenital Hyperinsulinism Sequencing Panel We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered on our PGxome Custom Panel. Parental targeted testing for all probands with uncertain, likely pathogenic or pathogenic variants in the ABCC8 and KCNJ11 genes are free of charge. For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page. The great majority oftests are completed within 20 days. In a cohort of 417 CHI patients studied at the Hyperinsulinism Center in The Childrens Hospital of Philadelphia (CHOP) (Snider et al. 2013), all nine genes were tested. Mutations were identified in 91% (272 of 298) of diazoxide-unresponsive probands (ABCC8, KCNJ11, and GCK), and in 47% (56 of 118) of diazoxide-responsive probands (ABCC8, KCNJ11, GLUD1, HADH, UCP2, HNF4A, and HNF1A). In another cohort of 300 CHI patients studied in United Kingdom (Kapoor et al. 2013), mutations were identified in 45.3% of patients (136/300) in eight tested genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A).KATP (ABCC8 and KCNJ11) mutations were the most common genetic cause identified (109/300, 36.3%). Mutations in ABCC8/KCNJ11 were identified in 92 (87.6%) diazoxide-unresponsive patients (n=105). Among the diazoxide-responsive patients (n=183), mutations were identified in 41 patients (22.4%), including mutations in ABCC8/KCNJ11 (15), HNF4A (7), GLUD1 (16) and HADH (3). The great majority oftests are completed within 20 days. Clinical sensitivity for gross deletions and duplications in the HADH gene cannot be predicted as few patients h Continue reading >>

Congenital Hyperinsulinism

Congenital Hyperinsulinism

"PHHI" redirects here. It is not to be confused with Wheeler Army Airfield . Congenital hyperinsulinism ,CHI, is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. [4] [3] Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and most become apparent in early infancy. Mild cases can be treated by frequent feedings, more severe cases can be controlled by medications that reduce insulin secretion or effects [4] [5] Insulin (which this condition creates in excess) Hypoglycemia in early infancy can cause jitteriness, lethargy , unresponsiveness, or seizures . [1] The most severe forms may cause macrosomia in utero, producing a large birth weight, often accompanied by abnormality of the pancreas. Milder hypoglycemia in infancy causes hunger every few hours, with increasing jitteriness or lethargy. Milder forms have occasionally been detected by investigation of family members of infants with severe forms, adults with the mildest degrees of congenital hyperinsulinism have a decreased tolerance for prolonged fasting. Other presentations are: [4] [5] [3] [6] The variable ages of presentations and courses suggest that some forms of congenital hyperinsulinism, especially those involving abnormalities of KATP channel function, can worsen or improve with time the potential harm from hyperinsulinemic hypoglycemia depends on the severity, and duration. Children who have recurrent hyperinsulinemic hypoglycemia in infancy can suffer harm to the brain [4] The cause of congenital hyperinsulinism has been linked to anomalies in nine different genes. [7] The diffuse form of this condition is inherited via the autosomal recessive manne Continue reading >>

Parouse.com

Parouse.com

Location (UCSC)Chr 11: 17.39 17.48 MbChr 7: 46.1 46.18 Mb ATP-binding cassette transporter sub-family C member 8 is a proteinthat in humans is encoded by the ABCC8 gene.[5][6] ABCC8 orthologs [7]have been identified in all mammals for which complete genome data areavailable.The protein encoded by this gene is a member of the superfamily ofATP-binding cassette (ABC) transporters. ABC proteins transportvarious molecules across extra- and intra-cellular membranes. ABCgenes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP,ALD, OABP, GCN20, White). This protein is a member of the MRPsubfamily which is involved in multi-drug resistance. This proteinfunctions as a modulator of ATP-sensitive potassium channels andinsulin release. Mutations and deficiencies in this protein have beenobserved in patients with hyperinsulinemic hypoglycemia of infancy, anautosomal recessive disorder of unregulated and high insulinsecretion. Mutations have also been associated withnon-insulin-dependent diabetes mellitus type II, an autosomal dominantdisease of defective insulin secretion. Alternative splicing of thisgene has been observed; however, the transcript variants have not beenfully described.[8] 1 See also2 References3 External links4 Further reading ATP-binding cassette transporterSulfonylurea receptor ^ a b c GRCh38: Ensembl release 89: ENSG00000006071 - Ensembl, May2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040136 - Ensembl, May2017^ "Human PubMed Reference:".^ "Mouse PubMed Reference:".^ Glaser B, Chiu KC, Anker R, Nestorowicz A, Landau H, Ben-Bassat H,Shlomai Z, Kaiser N, Thornton PS, Stanley CA, et al. (Nov 1994)."Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cMcentromeric to the insulin gene". Nat Genet. 7 (2): 1858.doi:10.1038/ng0694-185. PMID792 Continue reading >>

Genetic Testing For Familial Hyperinsulinism | Blueprint Genetics

Genetic Testing For Familial Hyperinsulinism | Blueprint Genetics

Label the sample tube with your patients name, date of birth and the date of sample collection. Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue. Familial hyperinsulinism (FHI) is characterized by hypoglycemia that can have an onset neonatally or later during childhood. The disease presentation can vary considerably even within one family. It can present as severe with a very low glucose concentration or with variable and milder hypoglycemia. The clinical utility of this panel for familial hyperinsulinism is 50-60%. Most of the patients with familial hyperinsulinism have a mutatedABCC8gene, while mutations inKCNJ11, GLUD1 andHFN4Ahave each been found in approximately 5% of patients. Congenital isolated hyperinsulinism is the most common cause of severe and persistent hypoglycemia in neonatal period. The prevalence has been estimated at 1:50,000 live births, with much higher numbers in certain more homogenous populations. Infants of diabetic mothers may present with a clinical picture identical to that of FHI and this panel has differential diagnostic power to diagnose cases with genetic causes of transient hypoglycemia in newborns. This panel also includes the Glycogen Storage Disorder Panel genes for differential diagnostic purposes, since hepatomegaly due to glycogen storage disorder might not be visible in the newborn period. Furthermore, the panel includes genes relevant in additional related phenotypes such as maturity onset diabetes of the young (MODY) or exercise-induced hyperinsulinism. Insulinoma and drug-induced hypoglycemia should also be considered in later-onset hyperinsulinism phenotypes. Genes in the Hypoglycemia, Hyperinsulinism and Ketone Metabolism Panel and their clinical significance * Some, or all, Continue reading >>

Congenital Hyperinsulinism - Genetics Home Reference

Congenital Hyperinsulinism - Genetics Home Reference

What does it mean if a disorder seems to run in my family? What is the prognosis of a genetic condition? Congenital hyperinsulinism affects approximately 1 in 50,000 newborns. This condition is more common in certain populations, affecting up to 1 in 2,500 newborns. What information about a genetic condition can statistics provide? Why are some genetic conditions more common in particular ethnic groups? Congenital hyperinsulinism is caused by mutations in genes that regulate the release (secretion) of insulin, which is produced by beta cells in the . Insulin clears excess sugar (in the form of glucose) from the bloodstream by passing glucose into cells to be used as energy. congenital hyperinsulinism lead to over-secretion of insulin from beta cells. Normally, insulin is secreted in response to the amount of glucose in the bloodstream: when glucose levels rise, so does Congenital hyperinsulinism can have different inheritance patterns, usually depending on the form of the condition. At least two forms of the condition have been identified. The most common form is the diffuse form, which occurs when all of the beta cells in the pancreas secrete too much insulin. The focal form of congenital hyperinsulinism occurs when only some of the beta cells over-secrete insulin. congenital hyperinsulinism is inherited in an , which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Less frequently, the diffuse form is inherited in an , which means one copy of the altered gene in each cell is sufficient to cause the disorder. congenital hyperinsulinism is more complex. For most genes, both copies are t Continue reading >>

Familial Hyperinsulinism

Familial Hyperinsulinism

Synonyms: FHI, Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) Familial hyperinsulinism (referred to as FHI in this GeneReview) is characterized by hypoglycemia that ranges from severe neonatal-onset, difficult-to-manage disease to childhood-onset disease with mild symptoms and difficult-to-diagnose hypoglycemia. Neonatal-onset disease manifests within hours to two days after birth. Childhood-onset disease manifests during the first months or years of life. In the newborn period, presenting symptoms may be nonspecific, including seizures, hypotonia, poor feeding, and apnea. In severe cases, serum glucose concentrations are typically extremely low and thus easily recognized, whereas in milder cases, variable and mild hypoglycemia may make the diagnosis more difficult. Even within the same family, disease manifestations can range from mild to severe. Individuals with autosomal recessive familial hyperinsulinism, caused by pathogenic variants in either ABCC8 or KCNJ11 (FHI-KATP), tend to be large for gestational age and usually present with severe refractory hypoglycemia in the first 48 hours of life; affected infants usually respond only partially to diet or medical management (i.e., diazoxide therapy) and thus may require pancreatic resection. Individuals with autosomal dominant FHI-KATP tend to be appropriate for gestational age at birth, to present at approximately age one year (range: 2 days - 30 years), and to respond to diet and diazoxide therapy. Exceptions to both of these generalities have been reported. FHI-GCK, caused by pathogenic variants in GCK, may be much milder than FHI-KATP; however, some persons have severe, diazoxide-unresponsive hypoglycemia. FHI-HADH, caused by pathogenic variants in HADH, tends to be relatively mild, although severe case Continue reading >>

Congenital Hyperinsulinism

Congenital Hyperinsulinism

"PHHI" redirects here. It is not to be confused with Wheeler Army Airfield . Insulin (which this condition creates in excess) Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. [1] [2] Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and most become apparent in early infancy.Mild cases can be treated by frequent feedings, more severe cases can be controlled by medications that reduce insulin secretion or effects [1] [3] There are differenct types of congenital hyperinsulinism as indicated below: Hyperammonemic hyperinsulinism (glutamate dehydrogenase gain-of-function mutations) Beckwith-Wiedemann syndrome (thought to be due to hyperinsulinism but pathophysiology still uncertain: 11p15 mutation or IGF2 excess) Paternal SUR1 mutation with clonal loss of heterozygosity of 11p15 Paternal Kir6.23 mutation with clonal loss of heterozygosity of 11p15 Hypoglycemia in early infancy can cause jitteriness, lethargy , unresponsiveness, or seizures . [4] The most severe forms may cause macrosomia in utero, producing a large birth weight, often accompanied by enlargement of the heart ( cardiomegaly ) and liver . Milder hypoglycemia in infancy causes hunger every few hours, with increasing irritability or lethargy if feeding is delayed.Congenital hyperinsulinism often becomes apparent later via an inability to sleep through the night. Sometimes an unusual stress like an illness precipitates a severe hypoglycemic episode.Milder forms have occasionally been detected by investigation of family members of infants with severe forms. Adults with the mildest degrees of congenital hyperinsulinism may si Continue reading >>

Permanent Neonatal Diabetes Mellitus

Permanent Neonatal Diabetes Mellitus

Initial Posting: February 8, 2008; Last Update: July 29, 2016. Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype . Persistent hyperglycemia (plasma glucose concentration >150-200 mg/dL) in infants younger than age six months establishes the diagnosis of PNDM. Molecular testing is recommended: identification of pathogenic variant (s) in ABCC8 or KCNJ11 can guide treatment. Treatment of manifestations: Start rehydration and intravenous insulin infusion promptly after diagnosis. When the infant is stable and tolerating oral feedings begin subcutaneous insulin therapy. Children with pathogenic variants in ABCC8 or KCNJ11 can be treated with oral sulfonylureas; all others require long-term insulin therapy. High caloric intake is necessary for appropriate weight gain. Pancreatic enzyme replacement therapy is required for those with exocrine pancreatic insufficiency. Prevention of secondary complications: Aggressive treatment and frequent monitoring of blood glucose concentrations to avoid acute complications such as diabetic ketoacidosis and hypoglycemia and reduce the long-term complications of diabetes mellitus. Surveillance: Lifelong monitoring of blood glucose concentrations at least four times a day; periodic developmental evaluations. After age ten years, annual screen Continue reading >>

More in insulin