- Bilateral tonic-clonic seizure (HP:0002069): A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: TAS. (OMIM:610505)
- Concentric hypertrophic cardiomyopathy (HP:0005157): Hypertrophic cardiomyopathy with an symmetrical and concentric pattern of hypertrophy. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: IEA. (OMIM:610505)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. (OMIM:610505)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. (OMIM:610505)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:610505)
- Elevated lactate:pyruvate ratio (HP:0032653): An abnormal increase in the molar ratio of lactate to pyruvate in the blood circulation. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: TAS. (OMIM:610505)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: IEA. (OMIM:610505)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Respiratory failure (HP:0002878): A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: IEA. (OMIM:610505)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Dilated cardiomyopathy (HP:0001644): Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:610505)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: IEA. (OMIM:610505)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Rhabdomyolysis (HP:0003201): Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Decreased activity of mitochondrial complex III (HP:0011924): A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Poor suck (HP:0002033): An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: TAS. (OMIM:610505)
- Increased circulating lactate concentration (HP:0002151): Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35). Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Dyspnea (HP:0002094): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Decreased activity of mitochondrial complex I (HP:0011923): A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Respiratory insufficiency (HP:0002093). Evidence: IEA. (OMIM:610505)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: IEA. (OMIM:610505)
- Hyponatremia (HP:0002902): The concentration of sodium in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:17033963)
- Decreased fetal movement (HP:0001558): An abnormal reduction in quantity or strength of fetal movements. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Decreased activity of mitochondrial complex IV (HP:0008347): A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Neonatal hypotonia (HP:0001319): Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: TAS. (OMIM:610505)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: TAS. (OMIM:610505)
- Apathy (HP:0000741): Apathy is a quantitative reduction of interest, motivation and the initiation and persistence of goal-directed behavior, where often the accompanying emotions, thoughts, and social interactions are also diminished. The individual is typically non-reactive to provocations, positive or negative, and appears to not care. Distinguished from lethargy which involves lack of physical or mental energy. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: TAS. (OMIM:610505)
- Severe lactic acidosis (HP:0004900): A severe form of lactic acidemia. Evidence: PCS. Frequency: 2/2. (PMID:17033963)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. (OMIM:610505)
- Optic neuropathy (HP:0001138). Evidence: TAS. (OMIM:610505)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: PCS. Frequency: 1/2. (PMID:17033963)
These phenotypes are associated with the disease fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (OMIM:610505).