Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. Before treatment this results in high blood sugar levels in the body. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks.The cause of type 1 diabetes is unknown, but it is believed to involve a combination of genetic and environmental factors. The underlying mechanism involves an autoimmune destruction of the insulin-producing beta cells in the pancreas. Diabetes is diagnosed by testing the level of sugar or glycated hemoglobin (HbA1C) in the blood. Type 1 diabetes can be distinguished from type 2 by testing for the presence of autoantibodies.There is no known way to prevent type 1 diabetes. Treatment with insulin is required for survival. Insulin therapy is usually given by injection just under the skin but can also be delivered by an insulin pump. A diabetic diet and exercise are important parts of management. If left untreated, diabetes can cause many complications. Complications of relatively rapid onset include diabetic ketoacidosis and nonketotic hyperosmolar coma.
When TSNALP enzymatic activity is low, inorganic pyrophosphate (PPi) accumulates outside of cells in the extracellular matrix of bones and teeth, and inhibits formation of hydroxyapatite mineral, the main hardening component of bone, causing rickets in infants and children and osteomalacia (soft bones) and odontomalacia (soft teeth) in children and adults. PLP is the principal form of vitamin B6 and must be dephosphorylated by TNSALP before it can cross the cell membrane. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters, which can cause seizures. In some cases, a build-up of calcium pyrophosphate dihydrate (CPPD) crystals in the joint can cause pseudogout. Genetics
Perinatal and infantile hypophosphatasia are inherited as autosomal recessive traits with homozygosity or compound heterozygosity for two defective TNSALP alleles. The mode of inheritance for childhood, adult, and odonto forms of hypophosphatasia can be either autosomal dominant or recessive. Autosomal transmission accounts for the fact that the disease affects males and females with equal frequency. Genetic counseling is complicated by the disease’s variable inheritance pattern, and by incomplete penetration of the trait.Hypophosphatasia is a rare disease that has been reported worldwide and appears to affect individuals of all ethnicities. The prevalence of severe hypophosphatasia is estimated to be 1:100,000 in a population of largely Anglo-Saxon origin. The frequency of mild hypophosphatasia is more challenging to assess because the symptoms may escape notice or be misdiagnosed.