Phenotypes associated with the disease recurrent metabolic encephalomyopathic crises-rhabdomyolysis-cardiac arrhythmia-intellectual disability syndrome (OMIM:616878):
- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 14/14. (PMID:26805782;PMID:26805781)
- Cardiac arrest (HP:0001695): An abrupt loss of heart function. Evidence: TAS. (OMIM:616878)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:616878)
- Elevated circulating tetradecenoylcarnitine concentration (HP:6000476): The concentration of tetradecenoylcarnitine (C14:1) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 5/6. (PMID:26805782;PMID:26805781)
- 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: PCS. Frequency: 9/12. (PMID:26805781)
- Gait ataxia (HP:0002066): A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall. Evidence: TAS. (OMIM:616878)
- 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: PCS. Frequency: 2/2. (PMID:26805782;PMID:26805781)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 5/15. (PMID:26805782;PMID:26805781)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:616878)
- Lower limb spasticity (HP:0002061): Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis. Evidence: PCS. Frequency: 2/2. (PMID:26805782)
- Neurodegeneration (HP:0002180): Progressive loss of neural cells and tissue. Evidence: TAS. (OMIM:616878)
- Elevated circulating aldolase concentration (HP:0012544): Concentration of fructose 1,6-bisphosphate aldolase in the blood circulation above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:26805781)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 8/15. (PMID:26805782;PMID:26805781)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: PCS. (PMID:26805781)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 13/13. (PMID:26805782;PMID:26805781)
- Ventricular tachycardia (HP:0004756): A tachycardia originating in the ventricles characterized by rapid heart rate (over 100 beats per minute) and broad QRS complexes (over 120 ms). Evidence: PCS. Frequency: 4/12. (PMID:26805782;PMID:26805781)
- Incoordination (HP:0002311): A deficit in coordination of muscle movements. Coordination is defined as the orchestrated movement of multiple body parts as required to accomplish intended actions, like walking. Evidence: PCS. (PMID:26805781)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 6/6. (PMID:26805782;PMID:26805781)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 3/4. (PMID:26805782;PMID:26805781)
- Spastic diplegia (HP:0001264): Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:616878)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:616878)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/1. (PMID:26805782)
- Ventricular fibrillation (HP:0001663): Uncontrolled contractions of muscles fibers in the left ventricle not producing contraction of the left ventricle. Ventricular fibrillation usually begins with a ventricular premature contraction and a short run of rapid ventricular tachycardia degenerating into uncoordinating ventricular fibrillations. Evidence: TAS. (OMIM:616878)
- 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: PCS. Frequency: 1/1. (PMID:26805781)
- Bradycardia (HP:0001662): A slower than normal heart rate (in adults, slower than 60 beats per minute). Evidence: PCS. Frequency: 1/12. (PMID:26805781)
- Rhabdomyolysis (HP:0003201): Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream. Evidence: PCS. Frequency: 13/15. (PMID:26805782;PMID:26805781)
- Dysarthria (HP:0001260): 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: 2/2. (PMID:26805782;PMID:26805781)
- 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: 14/14. (PMID:26805782;PMID:26805781)
- 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: 9/11. (PMID:26805781)
- Elevated circulating acylcarnitine concentration (HP:0045045): Concentration of acylcarnitine in the blood circulation above the upper limit of normal. Evidence: PCS. (PMID:26805782)
- Prolonged QTc interval (HP:0005184): A longer than normal interval (corrected for heart rate) between the Q and T waves in the heart's cycle. Prolonged QTc can cause premature action potentials during late phase depolarizations thereby leading to ventricular arrhythmias and ventricular fibrillations. Evidence: PCS. Frequency: 8/13. (PMID:26805782;PMID:26805781)
- Premature pubarche (HP:0012411): The onset of growth of pubic hair at an earlier age than normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:616878)
- Premature thelarche (HP:0010314): Premature development of the breasts. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:616878)
- 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: PCS. Frequency: 3/11. (OMIM:616878;PMID:26805782)
- 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:26805781)
- 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: TAS. Frequency: Occasional (HP:0040283). (OMIM:616878)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: PCS. Frequency: 3/3. (PMID:26805781)
- 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: PCS. Frequency: 1/1. (PMID:26805782)
- Hyperactive deep tendon reflexes (HP:0006801). Evidence: TAS. (OMIM:616878)
- Clonus (HP:0002169): A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch. Evidence: PCS. Frequency: 1/1. (PMID:26805781)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 1/1. (PMID:26805782)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 6/6. (PMID:26805782;PMID:26805781)
- 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: TAS. (OMIM:616878)
- Myoglobinuria (HP:0002913): Presence of myoglobin in the urine. Evidence: PCS. Frequency: 2/2. (PMID:26805782;PMID:26805781)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 9/11. (PMID:26805781)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 11/14. (PMID:26805782;PMID:26805781)
- Torsade de pointes (HP:0001664): A type of ventricular tachycardia characterized by polymorphioc QRS complexes that change in amplitue and cycle length, and thus have the appearance of oscillating around the baseline in the EKG. Evidence: PCS. Frequency: 3/13. (PMID:26805782;PMID:26805781)
- Brisk reflexes (HP:0001348): Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal. Evidence: PCS. Frequency: 2/2. (PMID:26805781)
- 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: 1/1. (PMID:26805781)
- 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: 12/13. (PMID:26805782;PMID:26805781)
- Myopathic facies (HP:0002058): A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness. Evidence: PCS. Frequency: 4/4. (PMID:26805781)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 4/11. (PMID:26805782;PMID:26805781)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 2/12. (PMID:26805781)
- Status epilepticus (HP:0002133): 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: 1/1. (PMID:26805782)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/1. (PMID:26805781)
- Gait disturbance (HP:0001288): The term gait disturbance can refer to any disruption of the ability to walk. Evidence: PCS. (PMID:26805781)
- 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: Occasional (HP:0040283). (OMIM:616878)
- Premature ventricular contraction (HP:0006682): Premature ventricular contractions (PVC) or ventricular extrasystoles are premature contractions of the heart that arise in response to an impulse in the ventricles rather than the normal impulse from the sinoatrial (SA) node. Evidence: PCS. Frequency: 1/12. (PMID:26805781)
- Oral-pharyngeal dysphagia (HP:0200136). Evidence: TAS. (OMIM:616878)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: TAS. (OMIM:616878)
- Acute rhabdomyolysis (HP:0008942): An acute form of rhabdomyolysis. Evidence: PCS. (PMID:26805781)