• Journal of Interdisciplinary Genomics
• /
• 제6권2호
• /
• pp.37-41
• /
• 2024

Neonatal diabetes mellitus, or congenital diabetes mellitus, is a rare genetic disorder caused by abnormal β cell function and other causes. The symptoms of hyperglycemia that occur in neonatal diabetes. The symptoms of hyperglycemia that occur in neonatal diabetes may be transient or persistent. The most frequent genetic cause of neonatal diabetes characterized by abnormal β cell function is abnormalities at the 6q24 locus. Another possible cause is mutations in the ABCC8 or KCNJ11 genes, which code for potassium channels in pancreatic β cells. This underscores the importance of rapid genetic diagnosis following neonatal diabetes diagnosis and highlights the critical timing of sulfonylurea use.

• Clinical and Experimental Pediatrics
• /
• 제58권8호
• /
• pp.309-312
• /
• 2015

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium ($K_{ATP}$) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the $K_{ATP}$ channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

• Neonatal Medicine
• /
• 제28권1호
• /
• pp.41-47
• /
• 2021

Neonatal diabetes mellitus can be categorized as transient, permanent, or syndromic, and approximately half of the cases are transient. We present a case involving a term newborn who showed overt progression of transient neonatal diabetes mellitus, with complete remission within 6 months. On the second day of life, the patient presented with tachypnea, hyperglycemia, and decreased serum levels of C-peptide and insulin. Continuous subcutaneous infusion of insulin and continuous glucose monitoring were well tolerated. The patient showed a normal growth pattern, with no hyperglycemic or hypoglycemic episodes at 6 months of age. As it is rare and often asymptomatic, hyperglycemia may be attributed to various factors, including intrauterine environment, perinatal stress, and diverse genetic background. Therefore, consistent blood glucose monitoring and prompt early insulin therapy are crucial for any term newborns with persistent hyperglycemia, to prevent further diabetic complications. Moreover, continuous subcutaneous insulin infusion and the utilization of continuous glucose monitoring devices are the most effective and practical management strategies.

• Neonatal Medicine
• /
• 제28권2호
• /
• pp.94-98
• /
• 2021

Neonatal diabetes mellitus (NDM) is a rare disease that occurs at less than 6 months of age and is presumably caused by a mutation in the gene that affects pancreatic beta-cell function. Approximately 80% of NDM cases reveal a known genetic mutation, and mutations in potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) and ABCC8 affecting the pancreatic beta-cell adenosine triphosphate-sensitive potassium channel may be treated with oral sulfonylurea. Early recognition of mutations in KCNJ11 and ABCC8 is important because early administration of sulfonylurea can not only control blood glucose levels but also improve neurodevelopmental outcomes. In the present study, we report a case of NDM that initially presented as diabetic ketoacidosis at the age of 1 month, accompanied by seizures during hospitalization. After confirmation of the KCNJ11 gene mutation (c.989A>C), we started administering oral sulfonylurea (glimepiride) at the age of 2 months. After gradually increasing the dosage of glimepiride, insulin was discontinued at the age of 3 months. To date, the infant's blood glucose levels have been well controlled without significant hypoglycemic events. No further episodes of seizures have occurred, and his developmental status is favorable.

• Clinical and Experimental Pediatrics
• /
• 제54권4호
• /
• pp.179-182
• /
• 2011

Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes mellitus that presents within the first 6 months of life with remission in infancy or early childhood. TNDM is mainly caused by anomalies in the imprinted region on chromosome 6q24; however, recently, mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), have also been implicated in TNDM. Herein, we present the case of a male child with TNDM whose mutational analysis revealed a heterozygous c.3547C>T substitution in the ABCC8 gene, leading to an Arg1183Trp mutation in the SUR1 protein. The parents were clinically unaffected and did not show a mutation in the ABCC8 gene. This is the first case of a de novo ABCC8 gene mutation in a Korean patient with TNDM. The patient was initially treated with insulin and successfully switched to sulfonylurea therapy at 14 months of age. Remission of diabetes had occurred at the age of 16 months. Currently, the patient is 21 months old and is euglycemic without any insulin or oral hypoglycemic agents. His growth and physical development are normal, and there are no delays in achieving neurological and developmental milestones.

• The Korean journal of internal medicine
• /
• 제33권6호
• /
• pp.1143-1149
• /
• 2018

Background/Aims: The purpose of this study was to compare maternal and neonatal outcomes in Korean women with type 2 diabetes and nondiabetic controls. Methods: We performed a retrospective survey of 200 pregnancies in women with type 2 diabetes (n = 100) and nondiabetic controls (n = 100) who delivered from 2003 to 2010 at Cheil General Hospital & Women's Healthcare Center, Korea. We compared maternal characteristics as well as maternal and neonatal outcomes between groups matched by age, pre-pregnancy weight, body mass index, parity, and gestational age at delivery. Results: The number of infants that were small for gestational age and the rate of major congenital malformations were not significantly different. However, women with type 2 diabetes showed a slightly higher risk for primary caesarean section (35.0% vs. 18.0%, p = 0.006) as well as pre-eclampsia (10.0% vs. 2.0%, p = 0.017), infections during pregnancy (26.0% vs. 2.0%, p < 0.001), neonatal weight ($3,370{\pm}552.0$ vs. $3,196{\pm}543.3$, p = 0.025), large for gestational age (22.0% vs. 9.0%, p = 0.011), and macrosomia (15.0% vs. 5.0%, p = 0.018) compared to nondiabetic controls. Conclusions: Maternal and neonatal outcomes for women with type 2 diabetes were worse than those for nondiabetic controls. Diabetic women have a higher risk for primary caesarean section, pre-eclampsia, infections during pregnancy, large neonatal birth weight, large for gestational age, and macrosomia.

• 대한유전성대사질환학회지
• /
• 제1권1호
• /
• pp.23-27
• /
• 2001

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism recently demonstrated to be caused by mutations in the GLUT 2 gene for the glucose transporter protein 2 expressed in liver, pancreas, intestine, and kidney. This disease is characterized by hepatorenal glycogen accumulation, both fasting hypoglycemia as well as postprandial hyperglycemia and hyperglactosemia, and generalized proximal renal tubular dysfunctions. We report the first Korean patient with FBS diagnosed based on clinical manifestations and identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed having a neonatal diabetes mellitus due to hyperglycemia and glycosuria at 3 days after birth. In addition, newborn screening for galactosemia revealed hypergalactosemia. Thereafter, she has been managed with lactose free milk, insulin therapy. However, she failed to grow and her liver has been progressively enlarging. Her liver functions were progressively deteriorated with increased prothrombin time. Liver biopsy done at age 9 months indicated micronodular cirrhosis with marked fatty changes. She succubmed to hepatic failiure with pneumonia at 10 months of age. Laboratory tests indicated she had generalized proximal renal tubular dysfuctions; renal tubular acidosis, hypophosphatemic rickets, and generalized aminoaciduria. Given aforementioned findings, the diagnosis of FBS was appreciated at age of 2 months. The DNA sequencing analysis of the GLUT 2 gene using her genomic DNA showed a novel mutation at 5th codon; Lysine5 Stop (K5X).

• 셀메드
• /
• 제11권3호
• /
• pp.12.1-12.5
• /
• 2021

Gestational diabetes mellitus (GDM) has become one of the major public health problems for both mothers and children globally. Internationally, the frequency of excess weight and obesity has risen dramatically in women of childbearing age. There seems to be a greater risk of having GDM in overweight or obese women, resulting in problems during pregnancy, birth and neonatal development. Hospital management is a problem for obese pregnant females with GDM and places extra burdens on the healthcare sector. GDM can result in possible risks to the wellbeing of the mother, fetus, and infant, as well as clinically significant negative effects on the mental health of the mother. For females and their developing babies, diabetes may cause problems during pregnancy. Unsatisfactory diabetes control enhances the risk of complications and other birth related issues during pregnancy. It may also cause a woman to suffer severe complications. Numerous maternal and fetal effects are associated with GDM and multiple detection and management methods are also pursued globally in order to reduce the burden of health. An overview of gestational diabetes treatment is given in this review.

• Clinical and Experimental Pediatrics
• /
• 제53권3호
• /
• pp.432-436
• /
• 2010

일과성 신생아 당뇨병은 6번 염색체의 부친 이체성, 부친으로부터 유래한 염색체 6q24의 중복, ZAC 또는 HYMAI 유전자의 CpG 섬의 메틸화 결함에 의해 야기된다. 저자들은 고혈당, 거설증, 자궁내성장지연으로 발현되어 부친으로부터 유래된 HYMA1 유전자만을 보인 일과성 신생아 당뇨병 1례를 경험하였다. 생후 18일된 여아가 거설증과 반복되는 고혈당으로 입원하였다. 거설증과 함께 큰 대천문, 작은 턱, 두드러진 눈을 보였으며 혈중 포도당 농도는 200-300 mg/dL로 유지되다가 입원 2일 후부터 인슐린 투여 없이도 정상 범위로 유지되었다. 모체로부터 유래된 메틸화된 대립유전자 유무를 확인하기 위하여 말초 혈액으로부터 genomic DNA를 추출하여 bisulfite를 처리한 후, 메틸화 특이 중합 효소 연쇄 반응으로 HYMAI 유전자의 일부분을 증폭시키고, 제한 효소 BssHII를 이용한 제한 효소 절편 길이 다형성 (restriction fragment length polymorphism, RFLP) 분석을 이용하여 HYMAI 유전자의 메틸화 여부를 확인한 결과, HYMAI 유전자의 메틸화 결함을 보여 부친에서 유래된 HYMAI 유전자만을 갖고 있음을 확인하였다. HYMAI 유전자의 메틸화 검사를 통해 6번 염색체의 각인된 유전자가 증명되었으며 메틸화 결함으로 인해 일과성 신생아 당뇨병이 발생하였다.

• Clinical and Experimental Pediatrics
• /
• 제57권1호
• /
• pp.1-18
• /
• 2014

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.