glossary

ACIDOSIS: Elevated amounts of organic acids in the blood, which accumulate when food is not properly metabolized.

ADP: Adenosine diphosphate; the low energy product produced when ATP releases energy to the cell.

ADVOCATE: One who supports or defends a cause. One who pleads on behalf of another.

ALPER DISEASE: Progressive Infantile Poliodystrophy.Cases of Alper disease may be caused by disorders of oxidative phosphorylation,including mitochondrial DNA depletion syndromes.

APHASIA: Impaired or absent language function,usually referring to speech; which results from an injury to brain structuresusually in the dominant hemisphere (the side of the brain that controlslanguage function is usually the side opposite to the handedness of the personand is referred to as the dominant hemisphere by definition).

ATAXIA: Un-coordination; Inability to coordinate themuscles in voluntary movement.

ATP: Adenosine triphosphate; cellular energy isstored in the third phosphate bond. ATP is formed from ADP and phosphate in theprocess known as oxidative phosphorylation.

BARTH SYNDROME: Cardiomyopathy-Neutropenia Syndrome.Marked by elevated levels of 3-methylglutaconic acid in the blood and urine.

BETA-OXIDATION: A series of metabolic reactionsnecessary for burning fatty acids (fats).

CARNITINE:(beta-hydroxy-gamma-N-trimiethylamino-butyrate). Responsible for the transportof long chain fatty acids into mitochondria.

CLONUS: An abnormal movement characterized by rapidcontraction and relaxation of muscles.

CNS: Central nervous system (the brain and spinalcord).

COMPLEX I: NADH-Coenzyme Q oxidoreductase (part ofthe Electron Transport Chain).

COMPLEX II: Succinate dehydrogenase (part of theElectron Transport Chain).

COMPLEX III: Coenzyme Q-cytochrome c oxidoreductase(part of the Electron Transport Chain).

COMPLEX IV: Cytochrome c oxidase (COX) (part of theElectron Transport Chain).

COMPLEX V: ATP synthase (part of the ElectronTransport Chain).

COX: Cytochrome c oxidase (Complex IV).

CPEO: Chronic Progressive External OphthalmoplegiaSyndrome. The combination of ptosis and restricted eye movements is referred toas opthalmoplegia.

CYTOCHROME: A type of protein whose function is tocarry electrons or protons (hydrogen ions) by virtue of the reversiblecharging/discharging of an iron atom or iron/sulfur atoms in the center of theprotein. Cytrochromes are central molecules of electron transport in theprocess known as oxidative phosphorylation. The “chrome” means color, and thesecytochromes are divided into four groups. (a, b, c, d) according to theirability to absorb or transmit certain colors of light.

CYTOPATHIES: A pathologic process or disease of the cell or components of the cell.

DYSPHASIA: Lack of coordination in speech, and failure to arrange words in an understandable way; due to brain lesion. Aphasiais the complete or near complete absence of speech, and is used to describe a more severe situation than dysphasia.

DEMENTIA: loss of cognition and mental functions due to a disease or disease process.

DNA: Deoxyribonucleic acid; a two-stranded molecule that contain the genes that provide the blueprint for all of the structures andfunctions of a living being. Most human DNA is nDNA, which is a huge molecule that is folded tightly and stored in the nucleus of the cell. MtDNA is a muchsmaller molecule stored in the mitochondria.

mtDNA: Mitochondrial DNA contain the genes that code for some of the enzymes and some of the necessary molecules needed to makethose enzymes of the respiratory chain. Mitochondria are the only part of the body cell with their own separate and unique DNA. Regardless, most of themitochondria and the respiratory chain are coded by nDNA. MtDNA is inherited only from the mother.

nDNA: Nuclear DNA; located in the nucleus of the cell, this DNA contains the blueprints for cells which make up the body.

ELECTRON TRANSPORT CHAIN (ETC.): Also known as the respiratory chain: The mitochondrial enzymes (also known as complexes I, II,III and IV) that are needed to generate the electron and proton “gradient” that is utilized by complex V to generate ATP.

ENCEPHALOPATHY: Any disease of the brain.

ENZYME: A protein that speeds up a chemical reaction or causes a chemical change in another substance. Enzymes do their work withoutbeing changed or used up in the process.

GENE: The fundamental unit of heredity. Genes are located on strands of DNA found in the cells and mitochondria.

GLUTARIC ACIDEMIA II: See MAD.

HEMIANOPSIA: Loss of vision, due to brain malfunction, for the right or left portion of vision, which may involve eitheror both eyes.

HYPOTONIA: Poor muscle tone, such as seen in “floppybabies”.

KSS: Kearns-Sayre Syndrome, which is the combination of CPEO, cardiac conduction defects and progressive hearing loss, usually duetoo a large deletion in part of the mitochondrial DNA.

LACTATE or LACTIC ACID: A chemical that is formed when sugars are broken down for energy without the presence of adequate oxygen.Lactic acid cannot be used by the body and will accumulate in blood and urine.Lactic acid causes the muscle pain when one runs too fast for too long. In people with mitochondrial disorders, lactic acid forms when the oxidative capacity (ability to burn foods using oxidative phosphorylation) of the person is impaired.

LCFA: long chain fatty acids, which make up the vast majority of fats we consume in our diet.

LCAD: Long-Chain Acyl-CoA Dehydrongenase Deficiency.

LEIGH DISEASE OR SYNDROME: Subacute Necrotizing Encephalomyelopathy.

LHON: Leber Hereditary Optic Neuropathy.

LIC: Lethal Infantile Cardiomyopathy.

MAD: Multiple Acyl-CoA Dehydrogenase Deficiency.

MCAD: Medium-Chain Acyl-CoA Dehydrongenase Deficiency.

MELAS: Mitochondrial Encephalomyopathy LacticAcidosis and Strokelike Episodes.

MERRF: Myoclonic Epilepsy and Ragged-Red FiberDisease.

METABOLISM: The process of cells burning food to produce energy. This is similar to a car’s engine (the cell’s mitochondria)burning gasoline (the food we eat) to produce the energy or torque that turns the drive train that spins the car’s wheels (the energy we need to move andthink).

MITOCHONDRIA: A part of the cell (organelle) that is responsible for energy production. The organelle consists of two sets of membranes, a smooth continuous outer coat and an inner membrane arranged in tubules or in folds that form plate-like double membranes (cristae); the principal energy source of the cell, containing the cytochrome enzymes ofter minimal electron transport and the enzymes of the citric acid cycle, fatty acid oxidation, and oxidative phosphorylation. Responsible for converting nutrients into energy as well as many other specialized tasks.

MITOCHONDRIAL CYTOPATHY: Disease process characterized by mitochondrial dysfunction. The preferred general term for referring to mitochondrial diseases.

MITOCHONDRIAL ENCEPHALOPATHY: Disease process characterized by mitochondrial dysfunction in the brain.

MNGIE: Myoneurogastointestinal Disorder andEncephalopathy.

MYOCLONUS: A single spasm or twitching of a muscle.Myoclonus can be a single event (twitch) or repeated events. Myoclonus can be a normal event (the jerks that occur when we fall asleep) or an abnormal event(those that occur while awake, or those associated with seizures ormitochondrial diseases). Clonus is the repeated spasms of muscles, due to a seizure or increased muscle tone.

MYOPATHY: Any abnormal conditions or disease of the muscle tissues, which include the muscles over our bones (skeletal muscle) and the heart (cardiac muscle).

NARP: Neuropathy Ataxia and Retinitis Pigmentosa.

NYSTAGMUS: Involuntary, erratic eye movements.

PARENTAL EMPOWERMENT: Parents taking charge, assuming responsibility and exercising appropriate and rationale power in a situation.(i.e.: obtaining a second opinion, requesting copies of laboratory reports,requesting or rejecting a muscle biopsy).

PEARSON SYNDROME: A severe disease occurring in infancy affecting bone marrow and pancreas function. Infants with Pearsonsyndrome may develop KSS as they get older.

PHD: Pyruvate Dehydrogenase Deficiency.

PHOSPHORYLATION: The addition of phosphate to an organic compound, such as the addition of phosphate to ADP to form ATP (the function of complex V in the electron transport chain) or the addition of phosphate to glucose to produce glucose monophosphate, through the action of enzymes known as phosphotransferases or kinases.

POINT DELETION: The deletion of a single nucleotideamino acid on a gene.

POINT MUTATION: The substitution of one nucleotide for another nucleotide amino acid on a gene.

PTOSIS: Droopy eyelids.

RESPIRATORY CHAIN: See Electron Transport Chain.

SCAD: Short-Chain Acyl-CoA Dehydrogenase Deficiency.

SEIZURES : Disturbances of brain function, manifested as episodic impairment or loss of consciousness, abnormal movement, or sensorydisturbances. Caused by paroxysmal disturbances in the electrical activity of the brain.

• Myoclonic: Seizures characterized by jerking a body extremity or generalized tonic-clonic seizures within an hour or two of waking from sleep.

• Partial: (Formerly known as focalseizures.) The seizure is limited to one area in the brain. During this type of seizure, the child may experience a range of strange or unusual sensations including sudden, jerky movements of one body part, distortions in hearing or seeing, stomach discomfort, or a sudden sense of fear. Partial seizures are classified as either simple or complex. In simple partial seizures, there is no loss of consciousness. In partial complex seizures, consciousness is impaired.

• Petit-mal: Now called generalized absence seizures. These are characterized by 5 to 15 second lapses in consciousness.During an absence seizure, the child appears to be staring into space and the eyes may roll upwards. Absence seizures typically occur in childhood and resolve in adolescence. Absence seizures are rare in adults.

SNE: Subacute Necrotizing Encephalomyelopathy, or Leigh Disease or Syndrome.

SYNDROME: The aggregate of and symptoms associated with any morbid process and constituting together the picture of the disease.Syndromes can be, but are not necessarily the same as the disease. For example,titubation is a syndrome and never referred to as the disease, while myopathy can be used properly to describe a syndrome or a disease (although most prefer to further subclassify a myopathy in order to be more specific).

TITUBATION: The appearance of staggering or stumble.