Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.
Methylmalonic acidemias, also called methylmalonic acidurias, are a group of inherited metabolic disorders, that prevent the body from properly breaking down proteins and fats. This leads to a buildup of a toxic level of methylmalonic acid in body liquids and tissues. Due to the disturbed branched-chain amino acids (BCAA) metabolism, they are among the classical organic acidemias.
Newborn screening (NBS) is a public health program of screening in infants shortly after birth for conditions that are treatable, but not clinically evident in the newborn period. The goal is to identify infants at risk for these conditions early enough to confirm the diagnosis and provide intervention that will alter the clinical course of the disease and prevent or ameliorate the clinical manifestations. NBS started with the discovery that the amino acid disorder phenylketonuria (PKU) could be treated by dietary adjustment, and that early intervention was required for the best outcome. Infants with PKU appear normal at birth, but are unable to metabolize the essential amino acid phenylalanine, resulting in irreversible intellectual disability. In the 1960s, Robert Guthrie developed a simple method using a bacterial inhibition assay that could detect high levels of phenylalanine in blood shortly after a baby was born. Guthrie also pioneered the collection of blood on filter paper which could be easily transported, recognizing the need for a simple system if the screening was going to be done on a large scale. Newborn screening around the world is still done using similar filter paper. NBS was first introduced as a public health program in the United States in the early 1960s, and has expanded to countries around the world.
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.
Maple syrup urine disease (MSUD) is a rare, inherited metabolic disorder that affects the body's ability to metabolize amino acids due to a deficiency in the activity of the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex. It particularly affects the metabolism of amino acids—leucine, isoleucine, and valine. With MSUD, the body is not able to properly break down these amino acids, therefore leading to the amino acids to build up in urine and become toxic. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax due to the buildup of these amino acids.
A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the normal metabolic process. It can also be defined as inherited single gene anomaly, most of which are autosomal recessive.
Glutaric acidemia type 1 (GA1) is an inherited disorder in which the body is unable to completely break down the amino acids lysine, hydroxylysine and tryptophan. Excessive levels of their intermediate breakdown products can accumulate and cause damage to the brain, but particularly the basal ganglia, which are regions that help regulate movement. GA1 causes secondary carnitine deficiency, as glutaric acid, like other organic acids, is detoxified by carnitine. Mental retardation may occur.
Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics.
Argininosuccinic aciduria is an inherited disorder that causes the accumulation of argininosuccinic acid in the blood and urine. Some patients may also have an elevation of ammonia, a toxic chemical, which can affect the nervous system. Argininosuccinic aciduria may become evident in the first few days of life because of high blood ammonia, or later in life presenting with "sparse" or "brittle" hair, developmental delay, and tremors.
2,4 Dienoyl-CoA reductase deficiency is an inborn error of metabolism resulting in defective fatty acid oxidation caused by a deficiency of the enzyme 2,4 Dienoyl-CoA reductase. Lysine degradation is also affected in this disorder leading to hyperlysinemia. The disorder is inherited in an autosomal recessive manner, meaning an individual must inherit mutations in NADK2, located at 5p13.2 from both of their parents. NADK2 encodes the mitochondrial NAD kinase. A defect in this enzyme leads to deficient mitochondrial nicotinamide adenine dinucleotide phosphate levels. 2,4 Dienoyl-CoA reductase, but also lysine degradation are performed by NADP-dependent oxidoreductases explaining how NADK2 deficiency can lead to multiple enzyme defects.
3-Methylcrotonyl-CoA carboxylase deficiency also known as 3-Methylcrotonylglycinuria is an inborn error of leucine metabolism and is inherited through an autosomal recessive fashion. 3-Methylcrotonyl-CoA carboxylase deficiency is caused by mutations in the MCCC1 gene, formerly known as MMCA, or the MCCC2 gene, formerly known as MCCB. MCCC1 encodes the a-subunits of 3-methylcrotonyl-CoA carboxylase while MCCC2 encodes the b-subunits. The clinical presentation of 3-Methylcrotonyl-CoA carboxylase deficiency is varied, even within members of the same family.
Histidinemia is a rare autosomal recessive metabolic disorder caused by a deficiency of the enzyme histidase. Histidase is needed for the metabolism of the amino acid histidine. Although originally thought to be linked to multiple developmental disorders histidinemia is now accepted as a relatively benign disorder, leading to a reduction in the prevalence of neonatal screening procedures.
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.
Guanidinoacetate methyltransferase deficiency is an autosomal recessive cerebral creatine deficiency that primarily affects the nervous system and muscles. It is the first described disorder of creatine metabolism, and results from deficient activity of guanidinoacetate methyltransferase, an enzyme involved in the synthesis of creatine. Clinically, affected individuals often present with hypotonia, seizures and developmental delay. Diagnosis can be suspected on clinical findings, and confirmed by specific biochemical tests, brain magnetic resonance spectroscopy, or genetic testing. Biallelic pathogenic variants in GAMT are the underlying cause of the disorder. After GAMT deficiency is diagnosed, it can be treated by dietary adjustments, including supplementation with creatine. Treatment is highly effective if started early in life. If treatment is started late, it cannot reverse brain damage which has already taken place.
Organic acidemia is a term used to classify a group of metabolic disorders which disrupt normal amino acid metabolism, particularly branched-chain amino acids, causing a buildup of acids which are usually not present.
Urocanic aciduria is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme urocanase. It is a secondary disorder of histidine metabolism.
Ornithine aminotransferase deficiency is an inborn error of ornithine metabolism, caused by decreased activity of the enzyme ornithine aminotransferase. Biochemically, it can be detected by elevated levels of ornithine in the blood. Clinically, it presents initially with poor night vision, which slowly progresses to total blindness. It is believed to be inherited in an autosomal recessive manner. Approximately 200 known cases have been reported in the literature. The incidence is highest in Finland, estimated at 1:50,000.
Metascreen is an advanced non-invasive metabolic screening test distributed by Cordlife Group Limited ("Cordlife"). It can detect as many as 110 inborn errors of metabolism from a urine specimen. Cordlife owns the brand name and trademark, "Metascreen".
Combined malonic and methylmalonic aciduria (CMAMMA), also called combined malonic and methylmalonic acidemia is an inherited metabolic disease characterized by elevated levels of malonic acid and methylmalonic acid. However, the methylmalonic acid levels exceed those of malonic acid. CMAMMA is not only an organic aciduria but also a defect of mitochondrial fatty acid synthesis (mtFASII). Some researchers have hypothesized that CMAMMA might be one of the most common forms of methylmalonic acidemia, and possibly one of the most common inborn errors of metabolism. Due to being infrequently diagnosed, it most often goes undetected.
