Congenital Metabolic Diseases (CMD)

Congenital Metabolic Diseases (CMD)

Congenital metabolic diseases constitute a category of genetic disorders caused by altered functioning of a specific metabolic pathway. Most individuals affected by these inherited conditions possess a defective gene that causes a deficiency of enzymes. There are hundreds of different inherited metabolic diseases with diverse symptoms, prognosis, and therapies. In most cases, individuals affected by congenital metabolic diseases either produce a non-functioning form of an enzyme or do not produce an enzyme at all that is responsible for controlling a particular metabolic pathway, akin to a missing piece in an assembly line, making it difficult, or impossible, for the entire chain to function correctly.

The production of an enzyme is encoded by genes present in chromosomes. As known, our genetic heritage, contained in the nucleus of every cell in our body, contains the necessary information for its functioning. We inherit half of our genetic heritage from our mother and half from our father. It can happen that a particular gene carries incorrect, “damaged” information, and this can occur because this defect is passed on by one of the parents, or it occurs during conception, embryonic development, or fetal development. Sometimes these genetic defects affect a particular metabolic pathway; this term refers to the set of transformations that normally occur in the human body, which, through sequential biochemical reactions, act on food-derived products or pre-existing compounds, rendering them usable or preventing their accumulation.

These metabolic transformation processes are essential for the production of essential substances and for the elimination of toxic compounds in various organs, as well as for the production of energy within cells and for the proper functioning of many other processes.
So, returning to the example of a complex and well-organized assembly line, raw materials, semi-finished products, and waste materials are constantly used, produced, transported, and disposed of. For example, metabolism is responsible for transforming carbohydrates, proteins, and fats present in food to produce energy, to build tissues, or to convert excess nitrogen into waste products eliminated through urine. Among the various indispensable pieces of this assembly line are proteins called enzymes that enable the implementation of various metabolic reactions.

Glycogen storage diseases (GSDs) are a group of rare metabolic diseases (8 different types) that affect one in 100,000 newborns. They are caused by a deficiency or functional deficit of one of the enzymes involved in glycogen metabolism, which is a polymer consisting of numerous molecules of glucose (sugar) attached to each other in a branched form. Glycogen represents an important and readily available source of energy (glucose) for our body, but when its storage and utilization are not adequately controlled by enzymes, excessive and unregulated accumulation in tissues can occur (mainly in the liver, muscles, kidneys, and brain). Dysregulation of glycogen metabolism can therefore cause serious structural (enlargement of liver, spleen, kidneys) and metabolic alterations that can lead to excessive muscle fatigue, hypoglycemic crises requiring continuous eating, and renal failure.