Those with transient neonatal diabetes tend to have symptoms in the first few days or weeks of life, with affected children showing weight loss and signs of dehydration, along with high levels of sugar in the blood and urine. Some children also have high levels of ketones in the bood and urine, or signs of metabolic acidosis. Permanent neonatal diabetes starts slightly later, typicalaly around six weeks of age. Regardless of type, preterm infants tend to experience symptoms earlier, typically around one week of age.Neonatal diabetes is classified into three subtypes: permanent, transient, and syndromic; each with distinct genetic causes and symptoms.Syndromic neonatal diabetes is the term for diabetes as just one component of any of several complex syndromes that affect neonates, including IPEX syndrome, Wolcott-Rallison syndrome, and Wolfram syndrome. Symptoms vary widely based on the syndrome. Cause
Neonatal diabetes is a genetic disease, caused by genetic variations that were either spontaneously acquired or inherited from ones parents. At least 30 distinct genetic variants can result in neonatal diabetes. The development and treatment of neonatal diabetes will vary based on the particular genetic cause. Known genetic variants cause neonatal diabetes by five major mechanisms: Preventing the development of the pancreas or β cells, promoting β-cell death by autoimmunity or endoplasmic reticulum stress, preventing β cells from recognizing glucose or secreting insulin, or abnormal expression of the 6q24 region on chromosome 6. Mechanism
Most permanent neonatal diabetes cases are caused by variations in the ATP-sensitive potassium channel, KATP.
Hypodysfibrinogenemia, also termed congenital hypodysfibrinogenemia, is a rare hereditary fibrinogen disorder cause by mutations in one or more of the genes that encode a factor critical for blood clotting, fibrinogen. These mutations result in the production and circulation at reduced levels of fibrinogen at least some of which is dysfunctional. Hypodysfibrinogenemia exhibits reduced penetrance, i.e. only some family members with the mutated gene develop symptoms.The disorder is similar to a form of dysfibrinogenemia termed congenital dysfibrinogenemia. However, congenital dysfibrinogenemia differs form hypodysfibrinogenemia in four ways. Congenital dysfibrinogenemia involves: the circulation at normal levels of fibrinogen at least some of which is dysfunctional; a different set of causative gene mutations; a somewhat different mix of clinical symptoms; and a much lower rate of penetrance.Hypodysfibrinogenemia causes episodes of pathological bleeding and thrombosis due not only to low levels of circulating fibrinogen but also to the dysfunction of a portion of the circulating fibrinogen. The disorder can lead to very significant bleeding during even minor surgical procedures and women afflicted with the disorderoften suffer significant bleeding during and after giving child birth, higher rates of miscarriages, and menorrhagia, i.e. abnormally heavy bleeding during the menstrual period. Presentation
In a study of 32 individuals diagnosed with hypodysfibrinogenemia, 41% presented with episodic bleeding, 43% presented with episodic thrombosis, and 16% were asymptomatic, being detected by abnormal blood tests. Bleeding and thrombosis generally begin in adulthood with the average age at the time of presentation and diagnosis being 32 years.