ABMGG Medical Biochemical Genetics key terms

A genetic disorder, usually inherited in an autosomal recessive pattern, in which a defect in an enzyme, transporter, or cofactor disrupts a normal metabolic pathway, causing accumulation of toxic intermediates or deficiency of essential products.

A population-based public health program that tests dried blood spots from newborns for treatable congenital disorders, including many inborn errors of metabolism, so that presymptomatic treatment can prevent irreversible harm.

An analytic technique that ionizes molecules, selects specific precursor ions, fragments them, and measures product ions, allowing simultaneous quantification of many metabolites such as acylcarnitines and amino acids from a single sample.

A panel measuring carnitine esters of fatty acids in blood or plasma, used to detect disorders of fatty acid oxidation and organic acidemias by identifying abnormal species and patterns of acylcarnitines.

A small volume of capillary blood collected onto filter paper and dried, widely used for newborn screening and for follow-up metabolic testing because it is stable and easy to transport.

A quantitative chromatographic measurement of amino acids in plasma, urine, or cerebrospinal fluid that identifies characteristic elevations or deficiencies used to diagnose aminoacidopathies.

A gas chromatography–mass spectrometry test of urine or other fluids that detects and quantifies organic acids, revealing characteristic profiles that diagnose organic acidemias and related disorders.

A laboratory measurement of the catalytic activity of a specific enzyme in cells or tissue, often used to confirm a diagnosis suggested by metabolite testing or to support carrier detection.

Analysis of DNA to identify pathogenic variants in a gene, used to confirm diagnoses, define inheritance, guide family testing, and support prenatal or preimplantation testing.

A DNA change established by evidence to cause disease, distinct from benign variation, and used in clinical decision-making for diagnosis, prognosis, and reproductive planning.

A DNA change whose relationship to disease is not established, so it should not be used alone to make or exclude a diagnosis; interpretation may change as evidence accumulates.

A person with one pathogenic variant in a recessive gene who typically has no or mild symptoms but can pass the variant to offspring; couples at risk may be offered reproductive options.

A pattern in which disease occurs when both copies of a gene carry pathogenic variants; carrier parents each have a 25 percent chance of an affected child with each pregnancy.

A pattern in which a pathogenic variant on the X chromosome causes disease most often in males, while carrier females may be unaffected or variably affected depending on X-inactivation.

A union between close biological relatives, which increases the chance that both partners carry the same recessive pathogenic variant and thus raises the risk of affected offspring.

A process of providing information and support about genetic risks, testing options, and reproductive choices in a nondirective manner that respects the patient's values and decisions.

The ethical and legal requirement to obtain a patient's or family's voluntary agreement to testing or treatment after explaining purpose, benefits, risks, alternatives, and limits of confidentiality.

An abnormally elevated blood ammonia concentration, a medical emergency in metabolic disease that can cause vomiting, lethargy, encephalopathy, and death if not treated promptly.

A defect in one of the enzymes or transporters of the urea cycle that impairs conversion of ammonia to urea, causing hyperammonemia that may present in the newborn period or later.

A medication such as sodium phenylbutyrate or sodium benzoate that provides an alternative pathway for nitrogen excretion, lowering ammonia in urea cycle disorders and related conditions.

A group of disorders in which defective amino acid breakdown causes accumulation of organic acids, producing metabolic acidosis, ketosis, hyperammonemia, and neurologic symptoms.

A state of decreased blood pH due to accumulation of acid or loss of bicarbonate, often signaled by increased anion gap and frequently seen in organic acidemias and mitochondrial disorders.

A calculated difference between measured cations and anions in serum, used to classify metabolic acidosis and to suggest the presence of unmeasured acids such as lactate or organic acids.

A defect in the transport or breakdown of fatty acids for energy, causing hypoketotic hypoglycemia, muscle symptoms, and risk of acute decompensation during fasting or illness.

Low blood glucose accompanied by inappropriately low ketones, a hallmark of fatty acid oxidation defects and some hyperinsulinism states that requires urgent evaluation and glucose administration.

A core management strategy in fatty acid oxidation and other energy-deficiency disorders in which regular feeding and illness-day plans prevent catabolism and metabolic crisis.

Deficiency of phenylalanine hydroxylase or its cofactor causes phenylalanine accumulation; without early dietary treatment, it leads to intellectual disability, making newborn screening and lifelong therapy essential.

A cofactor required by phenylalanine hydroxylase and other enzymes; its deficiency can mimic phenylketonuria but requires different treatment, including neurotransmitter replacement.

Reduced synthesis of dopamine or serotonin, often from defects in biopterin metabolism or tyrosine hydroxylase, causing movement disorder, hypotonia, and developmental delay that may respond to replacement therapy.

A disorder of galactose metabolism, most often galactose-1-phosphate uridylyltransferase deficiency, that causes neonatal jaundice, liver injury, and sepsis and is managed by strict lactose and galactose restriction.

A defect in branched-chain alpha-ketoacid dehydrogenase causing accumulation of leucine, isoleucine, and valine, with neonatal encephalopathy and a characteristic sweet odor; treatment requires dietary restriction and acute management.

A disease impairing oxidative phosphorylation, often from nuclear or mitochondrial DNA defects, producing variable multisystem features such as lactic acidosis, myopathy, and encephalopathy.

A group of inherited defects in lysosomal enzymes or transporters that cause progressive accumulation of substrates and multisystem disease, some now treatable with enzyme replacement or substrate reduction.

Intravenous administration of a recombinant enzyme to replace a deficient activity in selected lysosomal storage disorders, reducing substrate accumulation and improving some clinical outcomes.

A written, family-held plan describing early warning signs and immediate steps such as stopping protein intake, giving glucose, and seeking care to prevent metabolic crisis during illness.

The amount of function remaining in a mutant enzyme, which often correlates with age of onset and severity and helps predict the clinical course of a metabolic disorder.

Reduced or absent activity of a specific enzyme caused by pathogenic variants, leading to blocked substrate conversion and downstream metabolic consequences.

The buildup of a substrate or upstream intermediate when a pathway is blocked, which can damage organs and produce the clinical features of many inborn errors of metabolism.

The proportion of unaffected individuals who test positive on a screening test; in newborn screening, high sensitivity is prioritized even though this rate can be substantial.