ABMGG Clinical Biochemical Genetics key terms

A heritable disorder caused by a defect in an enzyme, transporter, or cofactor needed for normal biochemical pathways, leading to accumulation of upstream metabolites, deficiency of downstream products, or both.

Population-based testing of dried blood spots from newborns to detect treatable congenital disorders before symptoms appear, allowing early intervention to prevent disability or death.

An analytical technique that ionizes compounds, separates them by mass-to-charge ratio in multiple stages, and quantifies them; in newborn screening it measures amino acids and acylcarnitines from a single dried blood spot.

A panel measuring carnitine esters of fatty acids of varying chain length in blood or plasma, used to detect fatty acid oxidation defects and organic acidemias by characteristic chain-length patterns.

Quantitative measurement of free amino acids in plasma, urine, or cerebrospinal fluid by chromatography or mass spectrometry, used to identify disorders such as phenylketonuria, maple syrup urine disease, and citrullinemia.

Detection and quantification of organic acids in urine, typically by gas chromatography-mass spectrometry, revealing characteristic excretion patterns that diagnose organic acidemias and some fatty acid oxidation disorders.

A combined technique that separates volatile compounds by gas chromatography and identifies them by mass spectral fragmentation patterns; widely used for urine organic acid and other metabolite profiling.

Blood collected onto filter paper and air-dried, allowing stable transport and storage; the standard specimen for newborn screening and useful for remote or retrospective biochemical testing.

A laboratory measurement of catalytic activity in cells or tissue, often using fluorogenic or chromogenic substrates, used to confirm diagnoses such as lysosomal storage disorders and to assess residual function.

The fraction of normal catalytic function remaining in a patient's enzyme, which often correlates with severity and can distinguish attenuated from severe phenotypes in many metabolic disorders.

The relationship between specific genetic variants and the observable clinical or biochemical features they produce, used to predict prognosis and guide monitoring and treatment decisions.

A genetic change whose association with disease has not been established; it should not be used alone to make a diagnosis or alter management without additional biochemical or segregation evidence.

Follow-up biochemical or molecular analysis performed after an abnormal screening result to establish or exclude a diagnosis before initiating lifelong treatment.

The proportion of unaffected individuals who test abnormal on a screening test; in newborn screening it drives parental anxiety and follow-up costs and is balanced against sensitivity.

The probability that a positive screening result truly reflects disease, which depends on test sensitivity and specificity and on the prevalence of the disorder in the screened population.

An autosomal recessive disorder of phenylalanine hydroxylase or its cofactor that causes phenylalanine accumulation and, if untreated, intellectual disability; managed with dietary phenylalanine restriction and monitoring.

A cofactor required by phenylalanine hydroxylase and other aromatic amino acid hydroxylases; its deficiency causes hyperphenylalaninemia with neurotransmitter depletion and requires distinct treatment from classic phenylketonuria.

An autosomal recessive defect of branched-chain alpha-ketoacid dehydrogenase causing accumulation of leucine, isoleucine, and valine; classic forms present in the neonatal period with encephalopathy and a sweet urine odor.

Leucine, isoleucine, and valine, which share a catabolic pathway; leucine is the most neurotoxic when elevated, so treatment of maple syrup urine disease focuses on strict leucine control.

A group of disorders in which defective amino acid or fatty acid catabolism causes accumulation of organic acids, producing metabolic acidosis, hyperammonemia, and encephalopathy during catabolic stress.

A defect in one of the enzymes or transporters that convert ammonia to urea, causing hyperammonemia that can lead to cerebral edema, vomiting, and lethargy, especially after protein loading or illness.

Elevated blood ammonia, which is neurotoxic and may cause vomiting, lethargy, seizures, and coma; urgent measurement and treatment are required when a metabolic disorder is suspected.

A drug such as sodium phenylbutyrate or sodium benzoate that provides an alternative pathway for waste nitrogen excretion, lowering ammonia in urea cycle disorders when the normal pathway is impaired.

A disorder of mitochondrial fatty acid breakdown, such as medium-chain acyl-CoA dehydrogenase deficiency, that causes hypoketotic hypoglycemia and can progress to liver failure or cardiac arrhythmia during fasting.

Low blood glucose with inappropriately low ketone production, a hallmark of fatty acid oxidation defects and some hyperinsulinism disorders that signals impaired fat-derived fuel supply during fasting.

A small molecule that shuttles long-chain fatty acids into mitochondria for oxidation; primary or secondary deficiency impairs fatty acid oxidation and can cause muscle weakness, cardiomyopathy, and hypoketotic hypoglycemia.

A group of inherited defects in lysosomal enzymes, transporters, or cofactors that cause undegraded substrates to accumulate, producing progressive multisystem disease such as organomegaly, neurodegeneration, or skeletal changes.

Treatment that supplies a functional form of a deficient enzyme, often as an intravenous infusion, to reduce substrate accumulation in disorders such as Gaucher disease and Pompe disease.

The buildup of a metabolite upstream of a blocked enzymatic step, which drives much of the pathology in metabolic disease and serves as a target for therapies that reduce or divert the substrate.

A nonprotein molecule such as a vitamin derivative required for enzyme activity; cofactor defects can mimic primary enzyme deficiencies and may respond to supplementation with the cofactor or its precursor.

Acute deterioration of a previously stable metabolic disorder, often triggered by infection, fasting, or surgery, with vomiting, lethargy, acidosis, or encephalopathy requiring urgent intervention.

A written emergency plan that reduces protein or substrate intake and supplies calories and fluids during illness to prevent catabolism and decompensation in patients with metabolic disorders.

Controlled limitation of a specific nutrient, such as phenylalanine or leucine, to keep toxic metabolites within safe ranges while supporting growth, requiring frequent monitoring and dietitian involvement.

A specialist who designs and monitors medical nutrition therapy for metabolic disorders, calculating nutrient intake, prescribing medical foods, and adjusting diets during illness or growth transitions.

Testing an asymptomatic person for a heterozygous pathogenic variant, offered to relatives of affected individuals or to couples based on ancestry or family history to inform reproductive risk.

A pattern in which two pathogenic variants, one from each parent, are required for disease; carriers are typically unaffected and each offspring of two carriers has a one-in-four risk of being affected.

A process of helping patients and families understand a genetic condition, its inheritance, testing options, and reproductive risks, and supporting informed decisions while addressing emotional and ethical concerns.

The responsible selection and use of laboratory tests so that results meaningfully guide care, avoiding unnecessary testing while ensuring appropriate follow-up of abnormal or critical values.