- 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: 6/6. (PMID:18179882)
- 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: 2/5. (PMID:18179882)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 9/9. (PMID:18179882)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: IEA. (OMIM:618237)
- 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: PCS. Frequency: 5/5. (PMID:18179882)
- Flexion contracture (HP:0001371): A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. Evidence: IEA. (OMIM:618237)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: IEA. (OMIM:618237)
- 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: PCS. Frequency: 1/1. (PMID:18179882)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 5/5. (PMID:18179882)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. (PMID:18179882)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 5/5. (PMID:18179882)
- Irritability (HP:0000737): An emotional state characterized by negative feelings of heightened frustration, annoyance, or feeling upset, often triggered by internal factors (e.g., fatigue, hunger, unfulfilled desires) or external factors (e.g., social or environmental challenges). Irritability may be unpredictable, and is accompanied by a lowered threshold for emotional reactivity and observable features (speech, facial expressions, or psychomotor activity). Evidence: PCS. (PMID:18179882)
- Reduced eye contact (HP:0000817): A reduced frequency or duration of eye contact. Evidence: PCS. Frequency: 5/5. (PMID:18179882)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: PCS. Frequency: 9/9. Onset: Congenital onset (HP:0003577). (PMID:18179882)
- CNS demyelination (HP:0007305): A loss of myelin from nerve fibers in the central nervous system. Evidence: PCS. Frequency: 1/1. (PMID:18179882)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. (PMID:18179882)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. (PMID:18179882)
- 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: 9/9. (PMID:18179882)
- 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: 4/4. (PMID:18179882)
- 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: 1/6. Onset: Childhood onset (HP:0011463). (PMID:18179882)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. (PMID:18179882)
- 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:18179882)
- 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: PCS. (PMID:18179882)
- Intrauterine growth retardation (HP:0001511): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: IEA. (OMIM:618237)
- Neonatal death (HP:0003811): Death within the first 28 days of life. Evidence: PCS. Frequency: 3/9. (PMID:18179882)
These phenotypes are associated with the disease mitochondrial complex I deficiency, nuclear type 15 (OMIM:618237).