Pathophysiology
Normal carbohydrate balance and maintenance of blood glucose levels
Glycogen in liver and (to a lesser degree) kidneys serves as a form of stored, rapidly accessible glucose, so that the blood glucose level can be maintained between meals. For about 3 hours after a carbohydrate-containing meal, high insulin levels direct liver cells to take glucose from the blood, to convert it to glucose-6-phosphate (G6P) with the enzyme glucokinase, and to add the G6P molecules to the ends of chains of glycogen (glycogen synthesis). Excess G6P is also shunted into production of triglycerides and exported for storage in adipose tissue as fat. When digestion of a meal is complete, insulin levels fall, and enzyme systems in the liver cells begin to remove glucose molecules from strands of glycogen in the form of G6P. This process is termed glycogenolysis. The G6P remains within the liver cell unless the phosphate is cleaved by glucose-6-phosphatase. This dephosphorylation reaction produces free glucose and free PO4 anions. The free glucose molecules can be transported out of the liver cells into the blood to maintain an adequate supply of glucose to the brain and other organs of the body. Glycogenolysis can supply the glucose needs of an adult body for 12–18 hours. When fasting continues for more than a few hours, falling insulin levels permit catabolism of muscle protein and triglycerides from adipose tissue. The products of these processes are amino acids (mainly alanine), free fatty acids, and lactic acid. Free fatty acids from triglycerides are converted to ketones, and to acetyl-CoA.
Aspartylglucosaminuria (AGU) is an inherited disease that is characterized by a decline in mental functioning, accompanied by an increase in skin, bone and joint issues. The disease is caused by a defect in an enzyme known as aspartylglucosaminidase. This enzyme plays a significant role in our bodies because it aids in breaking down certain sugars (for example, oligosaccharides) that are attached to specific proteins (for example, glycoproteins). Aspartylglucosaminuria itself is characterized as a lysosomal disease because it does deal with inadequate activity in an enzymes function. Aspartylglucosaminidase functions to break down glycoproteins. These proteins are most abundant in the tissues of the body and in the surfaces of major organs, such as the liver, spleen, thyroid and nerves. When glycoproteins are not broken down, aspartylglucosaminidase backs up in the lysosomes along with other substances. This backup causes progressive damage to the tissues and organs. Signs and symptoms
At birth, there is no sign that a child will develop symptoms of aspartylglucosaminuria. Typically, signs and symptoms become apparent between two and four years of age and become progressively worse as the individual ages.