- 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:35708)
- Decreased CSF homovanillic acid concentration (HP:0003785): Decreased concentration of homovanillic acid (HVA) in the cerebrospinal fluid. HVA is a metabolite of dopamine. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:35708)
- Decreased CSF 5-hydroxyindolacetic acid concentration (HP:0025455): 5-HIAA (5-hydroxyindolacetic acid) concentration in the cerebrospinal fluid (CSF) is below the lower limit of normal. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:35708)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- Hyperhidrosis (HP:0000975): Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- 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:35708)
- 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: Frequent (HP:0040282). (ORPHA:35708)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- 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: Frequent (HP:0040282). (ORPHA:35708)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- 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: Frequent (HP:0040282). (ORPHA:35708)
- Sleep disturbance (HP:0002360): An abnormal pattern in the quality, quantity, or characteristics of sleep. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- Oculogyric crisis (HP:0010553): An acute dystonic reaction with blepharospasm, periorbital twitches, and protracted fixed staring episodes. There may be a maximal upward deviation of the eyes in the sustained fashion. Oculogyric crisis can be triggered by a number of factors including neuroleptic medications. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:35708)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Miosis (HP:0000616): Abnormal (non-physiological) constriction of the pupil. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Autistic behavior (HP:0000729): Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Increased circulating prolactin concentration (HP:0000870): The presence of abnormally increased levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland that plays a role in breast development and lactation during pregnancy. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Diminished deep tendon reflex (HP:0001315): A reduction (hyporeflexia) or complete absence (areflexia) of the involuntary muscle contraction normally elicited by a reflex stimulus, such as tapping a deep tendon. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Nasal congestion (HP:0001742): Reduced ability to pass air through the nasal cavity often leading to mouth breathing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Constipation (HP:0002019): Infrequent or difficult evacuation of feces. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Drooling (HP:0002307): Habitual flow of saliva out of the mouth. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- EEG abnormality (HP:0002353): Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Hypokinesia (HP:0002375): Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Limb hypertonia (HP:0002509). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Hypotension (HP:0002615): Low Blood Pressure, vascular hypotension. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:35708)
- 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:35708)
- Tremor (HP:0001337): An unintentional, oscillating to-and-fro muscle movement about a joint axis. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:35708)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:35708)
- Joint contracture (HP:0034392): A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:35708)
These phenotypes are associated with the disease Aromatic L-amino acid decarboxylase deficiency (ORPHA:35708).