- Encephalopathy (HP:0001298, a Human Phenotype Ontology term): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: PCS. (PMID:30245030)
- Mutism (HP:0002300, a Human Phenotype Ontology term): Complete lack of speech or verbal communication in a person despite attempts to engage in conversation. Mutism as a phenomena assumes the individual has previous capacity for speech and in the pediatric population it assumes that the person is past the age of typical language development. Evidence: IEA. (OMIM:618253)
- Poor speech (HP:0002465, a Human Phenotype Ontology term). Evidence: PCS. (PMID:30245030)
- Progressive neurologic deterioration (HP:0002344, a Human Phenotype Ontology term). Evidence: PCS. (PMID:30245030)
- Congenital onset (HP:0003577, a Human Phenotype Ontology term): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Seizure (HP:0001250, a Human Phenotype Ontology term): 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: PCS. Frequency: 2/4. (PMID:30245030)
- Infantile onset (HP:0003593, a Human Phenotype Ontology term): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Generalized hypotonia (HP:0001290, a Human Phenotype Ontology term): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Aspiration pneumonia (HP:0011951, a Human Phenotype Ontology term): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Sparse hair (HP:0008070, a Human Phenotype Ontology term): Reduced density of hairs. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Craniofacial dystonia (HP:0012179, a Human Phenotype Ontology term): A form of focal dystonia affecting the face and especially the jaw that is induced by the act of speaking. It is an involuntary contraction of the masticatory muscles, resulting in dysarthria or dysphagia. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Childhood onset (HP:0011463, a Human Phenotype Ontology term): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Irritability (HP:0000737, a Human Phenotype Ontology term): 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. Frequency: 1/4. (PMID:30245030)
- Hyperammonemia (HP:0001987, a Human Phenotype Ontology term): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Hypoglycemia (HP:0001943, a Human Phenotype Ontology term): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Ventriculomegaly (HP:0002119, a Human Phenotype Ontology term): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Metabolic acidosis (HP:0001942, a Human Phenotype Ontology term): 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. (PMID:30245030)
- Lactic acidosis (HP:0003128, a Human Phenotype Ontology term): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 2/4. (PMID:30245030)
- Axial hypotonia (HP:0008936, a Human Phenotype Ontology term): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Oligohydramnios (HP:0001562, a Human Phenotype Ontology term): Diminished amniotic fluid volume in pregnancy. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Dysphagia (HP:0002015, a Human Phenotype Ontology term): Difficulty in swallowing. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Status epilepticus (HP:0002133, a Human Phenotype Ontology term): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: PCS. Frequency: 2/4. (PMID:30245030)
- Cerebellar hypoplasia (HP:0001321, a Human Phenotype Ontology term): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Feeding difficulties (HP:0011968, a Human Phenotype Ontology term): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Bronchiectasis (HP:0002110, a Human Phenotype Ontology term): Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Dysarthria (HP:0001260, a Human Phenotype Ontology term): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Global developmental delay (HP:0001263, a Human Phenotype Ontology term): 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. (PMID:30245030)
- Increased circulating lactate concentration (HP:0002151, a Human Phenotype Ontology term): 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: 1/4. (PMID:30245030)
- Increased CSF lactate (HP:0002490, a Human Phenotype Ontology term): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 2/4. (PMID:30245030)
- Respiratory insufficiency (HP:0002093, a Human Phenotype Ontology term). Evidence: PCS. (PMID:30245030)
- Decreased activity of mitochondrial complex I (HP:0011923, a Human Phenotype Ontology term): A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. Evidence: PCS. (PMID:30245030)
- Reduced cerebral white matter volume (HP:0034295, a Human Phenotype Ontology term): An abnormally low volume of the white matter of the brain. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Motor regression (HP:0033044, a Human Phenotype Ontology term): Loss of previously achieved motor skills, as manifested by loss of developmental motor milestones. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Small for gestational age (HP:0001518, a Human Phenotype Ontology term): Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age. Evidence: PCS. Frequency: 2/4. (PMID:30245030)
- Autosomal recessive inheritance (HP:0000007, a Human Phenotype Ontology term): 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:30245030)
- Optic atrophy (HP:0000648, a Human Phenotype Ontology term): 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. Frequency: 2/4. (PMID:30245030)
- Loss of ambulation (HP:0002505, a Human Phenotype Ontology term): Inability to walk in a person who previous had the ability to walk. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Intrauterine growth retardation (HP:0001511, a Human Phenotype Ontology term): An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. Evidence: PCS. Frequency: 2/4. (PMID:30245030)
- Hypospadias (HP:0000047, a Human Phenotype Ontology term): 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: 1/4. (PMID:30245030)
- Spasticity (HP:0001257, a Human Phenotype Ontology term): A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Apnea (HP:0002104, a Human Phenotype Ontology term): 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: 1/4. (PMID:30245030)
- Decreased total neutrophil count (HP:0001875, a Human Phenotype Ontology term): Abnormal decrease of absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
- Simplified gyral pattern (HP:0009879, a Human Phenotype Ontology term): An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly. Evidence: PCS. Frequency: 1/4. (PMID:30245030)
These phenotypes are associated with the disease mitochondrial complex I deficiency, nuclear type 33 (OMIM:618253, an entry in Online Mendelian Inheritance in Man).