- 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: 1/10. (PMID:26510951)
- 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: TAS. (OMIM:220111)
- 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: 1/10. (PMID:26510951)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:220111)
- 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: 5/10. (PMID:26510951)
- 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:220111)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Hyperglycemia (HP:0003074): An increased concentration of glucose in the blood. Evidence: TAS. (OMIM:220111)
- Aortic valve atresia (HP:0010883): A congenital disorder of the aortic valve in which the orifice of the valve fails to develop. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Bicuspid aortic valve (HP:0001647): The presence of an aortic valve with two instead of the normal three cusps (flaps). Bicuspid aortic valvue is a malformation of a commissure (small space between the attachment of each cusp to the aortic wall) and the adjacent parts of the two corresponding cusps forming a raphe (the fused area of the two underdeveloped cusps turning into a malformed commissure between both cusps; the raphe is a fibrous ridge that extends from the commissure to the free edge of the two underdeveloped, conjoint cusps). Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: TAS. (OMIM:220111)
- Esodeviation (HP:0020045): A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Death in infancy (HP:0001522): Death within the first 24 months of life. Evidence: PCS. Frequency: 3/10. (PMID:26510951)
- Hirsutism (HP:0001007): Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair). Evidence: PCS. Frequency: 2/10. (PMID:26510951)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 6/10. (PMID:26510951)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: TAS. (OMIM:220111)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Truncal ataxia (HP:0002078): Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 7/10. (PMID:26510951)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- 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. Frequency: 10/10. (OMIM:220111)
- 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: 10/10. (PMID:26510951)
- Low anterior hairline (HP:0000294): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella. Evidence: IEA. (OMIM:220111)
- Midface retrusion (HP:0011800): Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. Evidence: TAS. (OMIM:220111)
- Bilateral superior vena cava (HP:0033379): The presence of a left and a right superior vena cava. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Peripheral demyelination (HP:0011096): A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system. Evidence: TAS. (OMIM:220111)
- 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:12529507)
- Partial agenesis of the corpus callosum (HP:0001338): A partial failure of the development of the corpus callosum. Evidence: PCS. Frequency: 1/6. (PMID:26510951)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- 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: 2/10. (PMID:26510951)
- Mitral regurgitation (HP:0001653): An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- 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: PCS. Frequency: 1/10. (PMID:26510951)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: TAS. (OMIM:220111)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Microvesicular hepatic steatosis (HP:0001414): A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes. Evidence: TAS. (OMIM:220111)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: IEA. (OMIM:220111)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 3/10. (PMID:26510951)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: IEA. (OMIM:220111)
- Dysmetria (HP:0001310): A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Ketonuria (HP:0002919): High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. (PMID:26510951)
- Mitral atresia (HP:0011560): A congenital defect with failure to open of the mitral valve orifice. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 3/10. (PMID:26510951)
- Ketosis (HP:0001946): Presence of elevated levels of ketone bodies in the body. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Fetal distress (HP:0025116): An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile. Evidence: PCS. Frequency: 3/10. (PMID:26510951)
- CNS demyelination (HP:0007305): A loss of myelin from nerve fibers in the central nervous system. Evidence: TAS. (OMIM:220111)
- Anteriorly placed anus (HP:0001545): Anterior malposition of the anus. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: TAS. Frequency: 10/10. (OMIM:220111)
- Persistent lactic acidosis (HP:0004898): A continuous form of lactic acidemia. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Prolonged partial thromboplastin time (HP:0003645): Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: PCS. Frequency: 1/6. (PMID:26510951)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 2/10. (PMID:26510951)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: PCS. (PMID:26510951)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 2/10. (PMID:26510951)
- Thickened nuchal skin fold (HP:0000474): A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold (NF) measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. An NF measurement greater than 5 mm at 14 to 17+6 weeks of gestation, or 6 mm at 18 to 28 weeks has been associated with a markedly increased risk for Down syndrome. Evidence: PCS. Frequency: 2/10. (PMID:26510951)
- 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: 1/10. (PMID:26510951)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Malar flattening (HP:0000272): Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation. Evidence: TAS. (OMIM:220111)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: TAS. (OMIM:220111)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: PCS. Frequency: 3/3. (PMID:26510951)
- Pulmonary edema (HP:0100598): Fluid accumulation in the lungs. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- 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: 1/10. (PMID:26510951)
- Motor regression (HP:0033044): Loss of previously achieved motor skills, as manifested by loss of developmental motor milestones. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Small for gestational age (HP:0001518): 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: 1/10. (PMID:26510951)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Left ventricular hypertrophy (HP:0001712): Enlargement or increased size of the heart left ventricle. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- 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: 10/10. (PMID:26510951)
- Increased hepatocellular lipid droplets (HP:0006565): An abnormal increase in the amount of intracellular lipid droplets in hepatocytes. Evidence: IEA. (OMIM:220111)
- Severe lactic acidosis (HP:0004900): A severe form of lactic acidemia. Evidence: PCS. Frequency: 1/10. (PMID:26510951)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 2/10. (PMID:26510951)
- Simplified gyral pattern (HP:0009879): 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: 1/6. (PMID:26510951)
These phenotypes are associated with the disease congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (OMIM:220111).