Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Galactosemia follows an autosomal recessive mode of inheritance that confers a deficiency in an enzyme responsible for adequate galactose degradation.
Galactokinase is an enzyme (phosphotransferase) that facilitates the phosphorylation of α-D-galactose to galactose 1-phosphate at the expense of one molecule of ATP. Galactokinase catalyzes the second step of the Leloir pathway, a metabolic pathway found in most organisms for the catabolism of α-D-galactose to glucose 1-phosphate. First isolated from mammalian liver, galactokinase has been studied extensively in yeast, archaea, plants, and humans.
Adenosine deaminase deficiency is a metabolic disorder that causes immunodeficiency. It is caused by mutations in the ADA gene. It accounts for about 10–20% of all cases of autosomal recessive forms of severe combined immunodeficiency (SCID) after excluding disorders related to inbreeding.
Galactose-1-phosphate uridyltransferase is an enzyme responsible for converting ingested galactose to glucose.
Isovaleric acidemia is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.
Short-chain acyl-coenzyme A dehydrogenase deficiency (SCADD) is an autosomal recessive fatty acid oxidation disorder which affects enzymes required to break down a certain group of fats called short chain fatty acids.
Autosomal recessive multiple epiphyseal dysplasia (ARMED), also called epiphyseal dysplasia, multiple, 4 (EDM4), multiple epiphyseal dysplasia with clubfoot or –with bilayered patellae, is an autosomal recessive congenital disorder affecting cartilage and bone development. The disorder has relatively mild signs and symptoms, including joint pain, scoliosis, and malformations of the hands, feet, and knees.
Carbamoyl phosphate synthetase I deficiency is an autosomal recessive metabolic disorder that causes ammonia to accumulate in the blood due to a lack of the enzyme carbamoyl phosphate synthetase I. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.
Sarcosinemia (SAR), also called hypersarcosinemia and SARDH deficiency, is a rare autosomal recessive metabolic disorder characterized by an increased concentration of sarcosine in blood plasma and urine ("sarcosinuria"). It can result from an inborn error of sarcosine metabolism, or from severe folate deficiency related to the folate requirement for the conversion of sarcosine to glycine. It is thought to be a relatively benign condition.
Purine nucleoside phosphorylase deficiency is a rare autosomal recessive metabolic disorder which results in immunodeficiency.
Galactose epimerase deficiency, also known as GALE deficiency, Galactosemia III and UDP-galactose-4-epimerase deficiency, is a rare, autosomal recessive form of galactosemia associated with a deficiency of the enzyme galactose epimerase.
D-Galactose-1-phosphate is an intermediate in the intraconversion of glucose and uridine diphosphate galactose. It is formed from galactose by galactokinase.The improper metabolism of galactose-1-phosphate is a characteristic of galactosemia. The Leloir pathway is responsible for such metabolism of galactose and its intermediate, galactose-1-phosphate. Deficiency of enzymes found in this pathway can result in galactosemia; therefore, diagnosis of this genetic disorder occasionally involves measuring the concentration of these enzymes. One of such enzymes is galactose-1-phosphate uridylyltransferase (GALT). The enzyme catalyzes the transfer of a UDP-activator group from UDP-glucose to galactose-1-phosphate. Although the cause of enzyme deficiency in the Leloir pathway is still disputed amongst researchers, some studies suggest that protein misfolding of GALT, which may lead to an unfavorable conformational change that impacts its thermal stability and substrate-binding affinity, may play a role in the deficiency of GALT in Type 1 galactosemia. Increase in galactitol concentration can be seen in patients with galactosemia; putting patients at higher risk for presenile cataract.
Essential fructosuria, caused by a deficiency of the enzyme hepatic fructokinase, is a clinically benign condition characterized by the incomplete metabolism of fructose in the liver, leading to its excretion in urine. Fructokinase is the first enzyme involved in the degradation of fructose to fructose-1-phosphate in the liver.
Galactose-1-phosphate uridylyltransferase deficiency(classic galactosemia) is the most common type of galactosemia, an inborn error of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridylyltransferase. It is an autosomal recessive metabolic disorder that can cause liver disease and death if untreated. Treatment of galactosemia is most successful if initiated early and includes dietary restriction of lactose intake. Because early intervention is key, galactosemia is included in newborn screening programs in many areas. On initial screening, which often involves measuring the concentration of galactose in blood, classic galactosemia may be indistinguishable from other inborn errors of galactose metabolism, including galactokinase deficiency and galactose epimerase deficiency. Further analysis of metabolites and enzyme activities are needed to identify the specific metabolic error.
Woodhouse–Sakati syndrome, is a rare autosomal recessive multisystem disorder which causes malformations throughout the body, and deficiencies affecting the endocrine system.
Antley–Bixler syndrome is a rare, severe autosomal recessive congenital disorder characterized by malformations and deformities affecting the majority of the skeleton and other areas of the body.
A galactosemic cataract is cataract which is associated with the consequences of galactosemia.
Inborn errors of carbohydrate metabolism are inborn error of metabolism that affect the catabolism and anabolism of carbohydrates.
Galactitol (dulcitol) is a sugar alcohol, the reduction product of galactose. It has a slightly sweet taste. In people with galactokinase deficiency, a form of galactosemia, excess dulcitol forms in the lens of the eye leading to cataracts.
Duarte galactosemia is an inherited condition associated with diminished ability to metabolize galactose due to a partial deficiency of the enzyme galactose-1-phosphate uridylyltransferase. DG differs from classic galactosemia in that patients with Duarte galactosemia have partial GALT deficiency whereas patients with classic galactosemia have complete, or almost complete, GALT deficiency. Duarte galactosemia (DG) is much more common than classic galactosemia, and is estimated to affect close to one in 4,000 infants born in the United States. Historically, most healthcare professionals have considered DG to be clinically mild based on pilot studies and anecdotal experience, and in 2019 a large study confirmed that children with DG are not at increased risk for developmental problems relative to children who do not have DG. Due to regional variations in newborn screening (NBS) protocols, some infants with DG are identified by NBS but others are not.
