Phenotypes associated with the disease Alacrimia-choreoathetosis-liver dysfunction syndrome (ORPHA:404454):
- 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: Frequent (HP:0040282). (ORPHA:404454)
- Hypotriglyceridemia (HP:0012153): An decrease in the level of triglycerides in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Abnormal myelination (HP:0012447): Any anomaly in the process by which myelin sheaths are formed and maintained around neurons. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Chronic constipation (HP:0012450): Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- 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: Frequent (HP:0040282). (ORPHA:404454)
- Decreased CSF protein concentration (HP:0025457): CSF total protein level is below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Decreased CSF albumin concentration (HP:0025458): CSF albumin level is below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- 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: Very rare (HP:0040284). (ORPHA:404454)
- Bilateral ptosis (HP:0001488). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- Corneal neovascularization (HP:0011496): Ingrowth of new blood vessels into the cornea. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- Lagophthalmos (HP:0030001): A condition in which the eyelids do not close to cover the eye completely. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- Decreased CSF biopterin level (HP:0040209): Concentration of biopterin in the cerebrospinal fluid (CSF) below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Facial hypotonia (HP:0000297): Reduced muscle tone of a muscle that is innervated by the facial nerve (the seventh cranial nerve). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Corneal scarring (HP:0000559). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Oculomotor apraxia (HP:0000657): Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancelation of the vestibulo-ocular reflex. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- 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). (ORPHA:404454)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Congenital hip dislocation (HP:0001374). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Hip dysplasia (HP:0001385): The presence of developmental dysplasia of the hip. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Micronodular cirrhosis (HP:0001413): A type of cirrhosis characterized by the presence of small regenerative nodules. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- 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. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Achilles tendon contracture (HP:0001771): A contracture of the Achilles tendon. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Reduced factor XI activity (HP:0001929): Decreased activity of coagulation factor XI. Factor XI, also known as plasma thromboplastin antecedent, is a serine proteinase that activates factor IX. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- 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: Occasional (HP:0040283). (ORPHA:404454)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Recurrent respiratory infections (HP:0002205): An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Athetosis (HP:0002305): A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Action tremor (HP:0002345): A tremor present when the limbs are active, either when outstretched in a certain position or throughout a voluntary movement. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- 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: Occasional (HP:0040283). (ORPHA:404454)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Coxa valga (HP:0002673): Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Generalized aminoaciduria (HP:0002909): An increased concentration of all types of amino acid in the urine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Acromesomelia (HP:0003086): Small hands and feet. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Limb joint contracture (HP:0003121): A contracture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Axonal loss (HP:0003447): A reduction in the number of axons in the peripheral nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Shoulder dislocation (HP:0003834): A displacement or misalignment of the humerus with respect to the other bones of the should joint. Note that a subluxation is a partial dislocation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Reduced bone mineral density (HP:0004349): A reduction of bone mineral density, that is, of the amount of matter per cubic centimeter of bones. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Reduced protein C activity (HP:0005543): An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein C. Protein C is activated to protein Ca by thrombin bound to thrombomodulin. Activated protein C degrades factors VIIIa and Va. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Prolonged prothrombin time (HP:0008151): Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Atonic seizure (HP:0010819): Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Focal emotional seizure with laughing (HP:0010821): Focal emotional seizure with laughing (gelastic) is characterized by bursts of laughter or giggling, usually without appropriate related emotion of happiness, and described as 'mirthless'. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Focal tonic seizure (HP:0011167): A type of focal motor seizure characterized by sustained increase in muscle contraction, lasting a few seconds to minutes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Hypofibrinogenemia (HP:0011900): Decreased concentration of fibrinogen in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Nodular regenerative hyperplasia of liver (HP:0011954): Diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Decreased resting energy expenditure (HP:0012340): A reduction in the number of calories used per unit time. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Astasia (HP:0020037): A postural abnormality characterized by the inability to stand without external support despite having sufficient muscle strength. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Delayed ability to sit (HP:0025336): A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Staring gaze (HP:0025401): An abnormality in which the eyes are held permanently wide open. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Fatigable weakness of speech muscles (HP:0030194): A type of weakness of the muscles involved in speech that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Suck reflex (HP:0030906): A type of primitive reflex that is elicited by lightly touching or tapping on the lips with an object such as a tongue blade, reflex hammer, or the examiner's finger. At times the reflex is obtained merely by approaching the lips with an object. A positive suck reflex consists of sucking movements by the lips when they are stroked or touched. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Lingual dystonia (HP:0031008): Involuntary protrusions, movements, spams and contortions of the tongue. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Tarsal sclerosis (HP:0031051): An elevation in bone density in one or more tarsal bones of the foot. Sclerosis is normally detected on a radiograph as an area of increased opacity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Impaired oral bolus formation (HP:0031146): An abnormality of swallowing characterized by reduced tongue coordination to form bolus after chewing. Food material spreads over the oral cavity instead of being concentrated into a bolus that is easily swallowed. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Impaired oropharyngeal swallow response (HP:0031162): Delay or absence of the swallow response, reflexes triggered by the contact the food bolus makes with the anterior faucial pillars. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Sclerosis of finger phalanx (HP:0100899): An elevation in bone density in one or more phalanges of the fingers. Sclerosis is normally detected on a radiograph as an area of increased opacity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:404454)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- Cone/cone-rod dystrophy (HP:0000548). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:404454)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:404454)
- Hyperkinetic movements (HP:0002487): Motor hyperactivity with excessive movement of muscles of the body as a whole. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:404454)
- Sensorimotor neuropathy (HP:0007141). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:404454)
- Alacrima (HP:0000522): Absence of tear secretion. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Decreased lacrimation (HP:0000633): Abnormally decreased lacrimation, that is, reduced tear production. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- 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:404454)
- 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: Frequent (HP:0040282). (ORPHA:404454)
- Choreoathetosis (HP:0001266): Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- 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:404454)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Generalized myoclonic seizure (HP:0002123): A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- 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: Frequent (HP:0040282). (ORPHA:404454)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Poor speech (HP:0002465). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Increased susceptibility to fractures (HP:0002659): An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- 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: Frequent (HP:0040282). (ORPHA:404454)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)
- Decreased circulating LDL-C concentration (HP:0003563): The concentration of low-density lipoprotein cholesterol in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:404454)