28.25 : Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake can prevent these complications, though learning difficulties may still occur.

Galactosemia is another metabolic disorder resulting from the deficiency or abnormality of liver enzymes required to convert galactose into glucose. Mutations in the GALE, GALK1, and GALT genes cause different types of galactosemia, with the most common being classic galactosemia due to a mutation in the GALT gene. This gene codes for the enzyme galactose-1-phosphate uridyltransferase, which is essential for breaking down galactose. Consequently, galactose accumulates in the blood, potentially causing life-threatening complications. Early intervention with a lactose-restricted diet can alleviate neonatal signs and prevent complications like liver failure and sepsis. However, developmental delays, speech problems, and motor function abnormalities may persist in children with classic galactosemia.

Glycogen storage disease is another metabolic disorder resulting from the absence of enzymes necessary to convert glycogen back into glucose. This deficiency leads to excessive glycogen accumulation, particularly in the liver and skeletal muscles, causing these organs to enlarge and impair their function.