Phenotypes associated with the disease mitochondrial complex I deficiency, nuclear type 1 (OMIM:252010):
- 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: 1/1. (PMID:11181577)
- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: IEA. (OMIM:252010)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: IEA. (OMIM:252010)
- 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: 3/3. (PMID:11181577;PMID:10944442)
- 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: IEA. (OMIM:252010)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Progressive macrocephaly (HP:0004481): The progressive development of an abnormally large skull. Evidence: IEA. (OMIM:252010)
- Cerebral edema (HP:0002181): Abnormal accumulation of fluid in the brain. Evidence: IEA. (OMIM:252010)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: IEA. (OMIM:252010)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: IEA. (OMIM:252010)
- Leukodystrophy (HP:0002415): Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies. Evidence: IEA. (OMIM:252010)
- Undetectable visual evoked potentials (HP:0007965). Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Exercise intolerance (HP:0003546): A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender. Evidence: IEA. (OMIM:252010)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: IEA. (OMIM:252010)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: IEA. (OMIM:252010)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Ragged-red muscle fibers (HP:0003200): An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm. Evidence: PCS. Frequency: 1/3. (PMID:11181577;PMID:10944442)
- Babinski sign (HP:0003487): Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract. Evidence: IEA. (OMIM:252010)
- Short chin (HP:0000331): Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- 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:10944442)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: IEA. (OMIM:252010)
- 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: PCS. Frequency: 1/1. (PMID:11181577)
- 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: 3/3. (PMID:11181577;PMID:10944442)
- Dyskinesia (HP:0100660): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: IEA. (OMIM:252010)
- 3-hydroxydicarboxylic aciduria (HP:0008160): The concentration of 2-hydroxydicarboxylic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: IEA. (OMIM:252010)
- 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: IEA. (OMIM:252010)
- Cyanosis (HP:0000961): Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood. Evidence: PCS. Frequency: 1/1. (PMID:11181577)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: PCS. Frequency: 1/1. (PMID:10944442)
- Spasticity (HP:0001257): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: IEA. (OMIM:252010)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: PCS. Frequency: 1/1. (PMID:11181577)
- Coma (HP:0001259): The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli. Evidence: IEA. (OMIM:252010)
- Optic neuropathy (HP:0001138). Evidence: IEA. (OMIM:252010)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Hepatic failure (HP:0001399). Evidence: IEA. (OMIM:252010)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: TAS. (OMIM:252010)
- Concentric hypertrophic cardiomyopathy (HP:0005157): Hypertrophic cardiomyopathy with an symmetrical and concentric pattern of hypertrophy. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- 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:10944442)
- Focal T2 hyperintense basal ganglia lesion (HP:0007183): A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 3/3. (PMID:11181577;PMID:10944442)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Blindness (HP:0000618): Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation. Evidence: IEA. (OMIM:252010)
- Mitochondrial inheritance (HP:0001427): A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy). Evidence: IEA. (OMIM:252010)
- 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: PCS. Frequency: 2/2. (PMID:10944442)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: IEA. (OMIM:252010)
- Lacticaciduria (HP:0003648): An increased concentration of lactic acid in the urine. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- 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: 2/2. (PMID:10944442)
- Tongue fasciculations (HP:0001308): Fasciculations or fibrillation affecting the tongue muscle. Evidence: PCS. Frequency: 1/1. (PMID:11181577)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: IEA. (OMIM:252010)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: IEA. (OMIM:252010)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 1/1. (PMID:11181577)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 2/2. (PMID:10944442)
- Respiratory insufficiency (HP:0002093). Evidence: IEA. (OMIM:252010)
- Focal T2 hypointense basal ganglia lesion (HP:0012752): A darker than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hypointensity affecting a particular region of the basal ganglia. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: PCS. Frequency: 1/1. (PMID:11181577)
- Increased intramyocellular lipid droplets (HP:0012240): An abnormal increase in intracellular lipid droplets In a muscle. The number and size of these drops can increase with somd disorders of lipid metabolism affecting muscle. See PMID 20691590 for histological images. Evidence: PCS. Frequency: 2/3. (PMID:11181577;PMID:10944442)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: IEA. (OMIM:252010)
- Increased CSF protein concentration (HP:0002922): Increased concentration of protein in the cerebrospinal fluid. Evidence: PCS. Frequency: 1/2. (PMID:10944442)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: IEA. (OMIM:252010)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. (OMIM:252010)
- Severe lactic acidosis (HP:0004900): A severe form of lactic acidemia. Evidence: PCS. Frequency: 1/1. (PMID:11181577)
- Acute necrotizing encephalopathy (HP:0006965). Evidence: IEA. (OMIM:252010)