Glossary

29 terms

MCADD Medium-chain acyl-CoA dehydrogenase deficiencyBasics

An inherited metabolic disorder that prevents the body from converting certain fats to energy, particularly during periods of fasting. It is caused by a deficiency of the MCAD enzyme.

MCAD enzyme Medium-chain acyl-CoA dehydrogenaseBiochemistry

The enzyme that metabolizes medium-chain fatty acids (those with 4 to 12 carbon atoms). It is essential for fatty acid β-oxidation and works inside mitochondria.

ACADM gene Genetics

The gene that provides instructions for making the MCAD enzyme. It is located on chromosome 1 (1p31.1). Other names include ACAD1, ACADM_HUMAN, MCAD, MCADH.

Autosomal recessive Genetics

A pattern of inheritance in which both copies of a gene carry a change for a person to be affected. Parents each carry one copy and typically do not show symptoms.

K304E c.985A>GGenetics

The most common disease-causing MCADD mutation, replacing lysine with glutamic acid at position 304 in the MCAD enzyme (current HGVS nomenclature: p.Lys329Glu / K329E). It is subject to a strong founder effect from northwestern Europe.

Fatty acid β-oxidation Biochemistry

The multistep process that breaks down fats and converts them to energy. MCAD catalyzes the first step in this cycle for medium-chain fatty acids.

Medium-chain fatty acids Biochemistry

Fatty acids with 4 to 12 carbon atoms, found in foods and body fat. They are the specific substrate of the MCAD enzyme.

Mitochondria Biochemistry

The energy-producing centers within cells, where the MCAD enzyme and fatty acid β-oxidation operate.

Acylcarnitines Diagnosis

Molecules formed when fatty acids that cannot be oxidized are attached to carnitine for transport out of mitochondria. Their levels in blood are used to screen for MCADD.

C8 OctanoylcarnitineDiagnosis

The hallmark accumulating acylcarnitine in MCADD and the primary biomarker used in newborn screening. It is the most sensitive and specific marker.

C6 HexanoylcarnitineDiagnosis

A secondary acylcarnitine marker that is also elevated in MCADD.

C10 DecanoylcarnitineDiagnosis

A secondary acylcarnitine marker that is also elevated in MCADD.

C10:1 DecenoylcarnitineDiagnosis

An acylcarnitine that is also elevated in some cases of MCADD.

Hypoglycemia Low blood glucoseBiochemistry

Low blood glucose. In MCADD it results from the inability to produce energy from fatty acid oxidation during fasting, together with depleted glycogen stores.

Hypoketotic hypoglycemia Biochemistry

Low blood glucose combined with inappropriately low ketone bodies — a characteristic feature of MCADD crises that distinguishes them from other causes of hypoglycemia.

Ketone bodies Biochemistry

Molecules the body makes from fat during fasting. In MCADD, ketone production is impaired, so ketones stay inappropriately low during a crisis.

Fasting Management

A period without food. Fasting is the most significant trigger for metabolic decompensation in MCADD.

Metabolic decompensation Biochemistry

A dangerous breakdown of metabolic control in which the body cannot make enough energy and partly processed fats build up, potentially damaging the liver and brain.

Newborn screening Diagnosis

Population screening performed shortly after birth. For MCADD it uses tandem mass spectrometry to analyze acylcarnitines from dried blood spots.

Tandem mass spectrometry MS/MSDiagnosis

An analytical technique used in newborn screening to measure acylcarnitine species from a dried blood spot, allowing detection of multiple metabolic disorders at once.

Dried blood spot Guthrie cardDiagnosis

A blood sample collected on filter paper (typically from a heel prick) and used for newborn screening.

Glycogen Biochemistry

The body’s stored form of glucose. Glycogen stores are depleted after several hours of fasting, after which fatty acid oxidation becomes a primary energy source.

MCTs Medium-chain triglyceridesManagement

Fats composed of medium-chain fatty acids (C6–C12), found in coconut oil, palm kernel oil, and some supplements. Orphanet (a Tier A source) recommends they should be avoided in MCADD.

Reye syndrome Basics

A severe disorder that may develop in children during apparent recovery from viral infections (associated with aspirin use). MCADD is sometimes mistaken for Reye syndrome.

Residual enzyme activity Research

The remaining MCAD enzyme activity a person has. Some observational studies suggest it may help predict clinical severity, but the genotype–phenotype relationship is incomplete.

Chemical chaperone Research

An approach that aims to stabilize a misfolded enzyme protein so it functions better. It is the rationale behind the experimental phenylbutyrate trials for the K304E variant.

Sodium phenylbutyrate ACER-001Research

An experimental drug being studied in Phase 2 trials as a potential treatment for MCADD. It is not an approved treatment.

Glycerol phenylbutyrate Ravicti™Research

An experimental drug studied as a chaperone therapy in a completed Phase 1 trial in MCADD patients with the K304E mutation. It is not an approved treatment.

Triheptanoin Research

An odd-chain triglyceride that was being investigated for preventing hypoglycemia in MCADD. Both trials were withdrawn before enrolling participants.