- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: IEA. (OMIM:210200)
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: PCS. Frequency: 1/1. (PMID:11181649)
- Decreased circulating carnitine concentration (HP:0003234): Concentration of carnitine in the blood circulation below the lower limit of normal. Evidence: PCS. Frequency: 3/3. (PMID:11181649;PMID:17968484)
- 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: 1/2. (PMID:17968484)
- Profound intellectual disability (HP:0002187): Profound intellectual disability (ID) is defined as a type of ID characterized by profoundly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) below 20. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- 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: IEA. (OMIM:210200)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 2/5. (PMID:11170888)
- Elevated circulating 3-hydroxyisovalerylcarnitine concentration (HP:0035028): Concentration of 3-hydroxyisovalerylcarnitine in the blood circulation above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:210200)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Severe postnatal growth retardation (HP:0008850): Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Generalized dystonia (HP:0007325): A type of dystonia that affects all or most of the body. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Episodic metabolic acidosis (HP:0004911): Repeated transient episodes of metabolic acidosis, that is, of the buildup of acid or depletion of base due to accumulation of metabolic acids. Evidence: IEA. (OMIM:210200)
- 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: IEA. (OMIM:210200)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 3/3. (PMID:11181649;PMID:17968484)
- Reduced 3-methylcrotonyl CoA carboxylase activity in cultured fibroblasts (HP:4000206): Activity of 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4) below the lower limit of normal in cultured fibroblasts. Evidence: PCS. Frequency: 2/2. (PMID:11181649;PMID:17968484)
- 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. Frequency: 1/1. (PMID:17968484)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 1/1. (PMID:11181649)
- 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:17968484)
- 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: 1/1. (PMID:17968484)
- Neonatal seizure (HP:0032807): A seizure occurring within the neonatal period (28 days beyond the full term date). Evidence: PCS. Frequency: 1/1. (PMID:11181649)
- 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: 1/2. (PMID:11181649;PMID:17968484)
- Abnormal CNS myelination (HP:0011400): An abnormality of myelination of nerves in the central nervous system. Evidence: PCS. Frequency: 0/1. (PMID:17968484)
- EEG with frontal focal spikes (HP:0012015): EEG with focal sharp transient waves of a duration less than 80 msec in the frontal region. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Hyperleucinemia (HP:0010911): The concentration of leucine in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Acute hyperammonemia (HP:0008281): An increased concentration of ammonia in the blood with sudden onset. Evidence: IEA. (OMIM:210200)
- 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:11181649)
- Apnea (HP:0002104): 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: IEA. (OMIM:210200)
- 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:11181649)
- Hypsarrhythmia (HP:0002521): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. Frequency: 1/1. (PMID:11181649)
- Stridor (HP:0010307): Stridor is a high pitched sound resulting from turbulent air flow in the upper airway. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- EEG with parietal focal spike waves (HP:0012012): EEG with focal sharp transient waves in the parietal region, i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Insomnia (HP:0100785): Persistent difficulty in starting or maintaining sleep, or waking up earlier than desired, despite having adequate opportunities and conditions for sleep. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- 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:210200)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- 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. Frequency: 1/1. (PMID:17968484)
- Elevated urinary 3-methylcrotonylglycine level (HP:0033596): An abnormally increased amount of 3-methylcrotonylglycine in the urine. Evidence: PCS. Frequency: 10/10. (PMID:11170888;PMID:11181649;PMID:17968484)
- 3-hydroxyisovaleric aciduria (HP:0033111): Concentration of 3-hydroxyisovaleric acid in the urine above the normal range. Evidence: PCS. Frequency: 10/10. (PMID:11170888;PMID:11181649;PMID:17968484)
- Acute hepatic steatosis (HP:0006573): An acute form of hepatic steatosis. Evidence: IEA. (OMIM:210200)
- Clonic seizure (HP:0020221): A clonic seizure is a type of motor seizure characterized by sustained rhythmic jerking, that is regularly repetitive. Evidence: PCS. Frequency: 1/1. (PMID:11181649)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: IEA. (OMIM:210200)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: TAS. (OMIM:210200)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Hyperreflexia (HP:0001347): Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Opisthotonus (HP:0002179): Opisthotonus is defined as a dramatic abnormal posture due to spastic contraction of the extensor muscles of the neck, trunk, and lower extremities that produces a severe backward arching from neck to heel. In most cases, the trunk is elevated off the ground by a few inches. It is usually sudden in onset and can be sustained or repetitive. It can be considered a variant of decerebrate posturing involving a hyperextension of the neck, back, and limbs. Evidence: IEA. (OMIM:210200)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/5. (PMID:11170888)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: IEA. (OMIM:210200)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Adult onset (HP:0003581): Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later. Evidence: PCS. Frequency: 2/5. (PMID:11170888)
- Hematuria (HP:0000790): The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine). Evidence: PCS. Frequency: 1/1. (PMID:17968484)
- Bilateral tonic-clonic seizure with generalized onset (HP:0025190): A bilateral tonic-clonic seizure with generalized onset is a type of bilateral tonic-clonic seizure characterized by generalized onset; these seizures rapidly engage networks in both hemispheres at the start of the seizure. Evidence: PCS. Frequency: 1/1. (PMID:11181649)
- Tonic seizure (HP:0032792): A tonic seizure is a type of motor seizure characterized by unilateral or bilateral limb stiffening or elevation, often with neck stiffening. Evidence: PCS. Frequency: 1/1. (PMID:11181649)
These phenotypes are associated with the disease 3-methylcrotonyl-CoA carboxylase 1 deficiency (OMIM:210200).