- 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: Frequent (HP:0040282). (ORPHA:70472)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Decreased liver function (HP:0001410): Reduced ability of the liver to perform its functions. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Chorea (HP:0002072): Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Progressive neurologic deterioration (HP:0002344). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Cytochrome C oxidase-negative muscle fibers (HP:0003688): An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Multifocal epileptiform discharges (HP:0010841): An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- EEG with abnormally slow frequencies (HP:0011203): EEG with abnormally slow frequencies. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Abnormality of movement (HP:0100022): An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:70472)
- Brachycephaly (HP:0000248): An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Congestive heart failure (HP:0001635): The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Abnormal cerebral morphology (HP:0002060): Any structural abnormality of the telencephalon, which is also known as the cerebrum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Orofacial dyskinesia (HP:0002310). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Obstructive sleep apnea (HP:0002870): Obstructive Sleep Apnea is a condition characterized by the obstruction of the airway and pauses in breathing during sleep, which occur multiple times throughout the night. It is related to the relaxation of muscle tone that typically happens during sleep, leading to a partial collapse of the soft tissues in the airway and causing airflow obstruction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Hypopigmentation of hair (HP:0005599). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Central sleep apnea (HP:0010536): Sleep apnea results from a temporary loss of the central drive to the muscles responsible for breathing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Gastrostomy tube feeding in infancy (HP:0011471): Feeding problem necessitating gastrostomy tube feeding. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Abnormal reproductive system morphology (HP:0012243): A structural or developmental anomaly of any of the tissues involved in the genital system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- Dyskinesia (HP:0100660): A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:70472)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- 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: Very frequent (HP:0040281). (ORPHA:70472)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- Stroke-like episode (HP:0002401): No consensus exists on what a stroke-like episode is, but these episodes can be functionally defined as a new neurological deficit, occurring with or without the context of seizures, which last longer than 24 hours. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- Increased CSF lactate (HP:0002490): Increased concentration of lactate in the cerebrospinal fluid. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- 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: Very frequent (HP:0040281). (ORPHA:70472)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
- Abnormal circulating enzyme concentration or activity (HP:0012379): Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:70472)
These phenotypes are associated with the disease Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type (ORPHA:70472).