Fructose intolerance and essential fructosuria Fruc-Fructose intolerance and essential fructosuria are genetic defects of fructose metabolism. Fructose intolerance is an autosomal recessive disease, caused by a genetic defect in fructose 1-phosphate aldolase (aldolase B) in the liver. The symptoms of aldolase B deficiency occur when the infant is exposed to fructose. Aldolase B deficiency results in phosphate depletion and fructose 1-phosphate accumulation in the liver. Consequently, gluconeogenesis and gly-cogenolysis are blocked, resulting in the inhibition of protein synthesis and subsequent liver failure.
Essential fructosuria is caused by a defect in the fructokinase gene. This disorder is asymptomatic and results in the excretion of fructose in the urine and in the conversion of fructose to fructose 6-phosphate in the muscle and adipose tissue.
Glucose and galactose malabsorption Carbohydrate intolerance is a hereditary disorder that occurs infrequently and poses serious health risks. This disorder is caused by a deficiency in a digestive enzyme (e.g., sucrase-a-dextrinase) and defective glucose-galactose transport. Carbohydrate intolerance presents as the development of profuse infant diarrhoea immediately after birth.
A lack of the enzyme glucose 6-phosphatase in the liver, kidney, and intestinal mucosa causes a disease known as Von Gierke's disease. This disease results in fasting hypoglycaemia, hepatomegaly, and recurrent acidosis. Genetic defects in glucose 6-phosphatase, glucose 6-phosphatase translocase, or pyrophosphate transporter result in a metabolic imbalance and an inability of the liver to maintain glucose homeostasis by either glycogenolysis or gluconeogenesis.
Gene mutations in the liver and muscle glycogen phosphorylases result in rare autosomal recessive disorders. In the liver, the disease results in glycogen accumulation and is known as Hers' disease. It is characterized by hypoglycaemia, hepatomegaly, and growth delay. In the muscle, the disease results in progressive muscle weakness and glycogen accumulation in the liver, and is known as McArdle's disease. It is characterized by exercise intolerance. A mutation in the debranching enzyme also results in glycogen accumulation in the liver and/or muscle and is known as Cori's disease. It is characterized by fasting hypoglycaemic convulsions, hepatome-lagy, and myopathy.
Diabetes mellitus is a group of metabolic disorders characterized by high levels of blood glucose (impaired glucose tolerance) and results from defects in insulin secretion, insulin action, or both. Diabetes mellitus is the seventh leading cause of death in the USA and is a major cause of premature mortality, stroke, cardiovascular disease, peripheral vascular disease, congenital malformations, perinatal mortality, and long-term and short-term disability. There are four principal types of diabetes mellitus: type 1 (formerly known as insulin-dependent diabetes mel-litus), type 2 (formerly known as noninsulin-dependent diabetes mellitus), gestational diabetes (GDM), and maturity-onset diabetes of the young (MODY).
Type 1 diabetes Type 1 diabetes is caused by autoimmune pancreatic ft cell exhaustion and loss of insulin secretion. Onset of the disease occurs when most of the pancreatic ft cells have been destroyed by the immune system. This form of diabetes is generally diagnosed in children and young adults and accounts for between 5% and 10% of all cases of diabetes mellitus.
Type 2 diabetes Type 2 diabetes is a complex het-erogenous disorder caused by interactions of various genetic and environmental factors. It is characterized by insulin resistance, obesity, a sedentary lifestyle, and occasionally by decreased insulin secretion. Because obesity and physical inactivity are increasing in children, the prevalence of paediatric type 2 diabetes has increased dramatically over the past 20 years to reach epidemic proportions. More than 85% of the cases of diabetes mellitus are type 2.
Gestational diabetes GDM is a form of glucose intolerance that is diagnosed in some pregnant women. It is usually ameliorated after childbirth, but it increases the risk of developing type 2 diabetes in the future.
Maturity-onset diabetes of the young MODY is an autosomal dominant trait that primarily affects insulin secretion and accounts for between 2% and 5% of the cases of diabetes. MODY can be caused by mutations in the glucokinase genes, leading to a reduced rate of glycolysis in the pancreas, reduced glycogen synthesis, and increased gluconeogenesis in the liver. It is diagnosed mostly in France and in the UK.
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