Phenotypes associated with the disease Niemann-Pick disease, type C1 (OMIM:257220):
- Foam cells (HP:0003651): The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance. Evidence: IEA. (OMIM:257220)
- 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: IEA. (OMIM:257220)
- 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: 12/14. (PMID:11182931)
- 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: PCS. Frequency: 4/4. (PMID:12408188)
- Unesterified cholesterol accumulation in cultured fibroblasts (HP:6000158): An abnormal result of the filipin test. This test is based on the reaction of unesterified cholesterol with fluorescent antibiotic filipin giving a strongly fluorescent, stable cholesterol-filipin complex suitable for in situ detection. An abnormal test result is present if there is a perinuclear accumulation of staining in lysosomal storage organelles (LSOs). Evidence: PCS. (PMID:25665455)
- Fetal ascites (HP:0001791): Accumulation of fluid in the peritoneal cavity during the fetal period. Evidence: IEA. (OMIM:257220)
- 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:257220)
- Neurofibrillary tangles (HP:0002185): Pathological protein aggregates formed by hyperphosphorylation of a microtubule-associated protein known as tau, causing it to aggregate in an insoluble form. Evidence: IEA. (OMIM:257220)
- 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. (PMID:11182931)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 7/13. (PMID:11182931)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:257220)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/4. (PMID:12408188)
- Low cholesterol esterification rate (HP:0003349): A reduction in the rate of cholesterol esterification. Evidence: PCS. Frequency: 13/13. (PMID:3378364;PMID:12408188)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: IEA. (OMIM:257220)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 4/13. (PMID:11182931)
- 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: 4/4. Onset: Juvenile onset (HP:0003621). (PMID:12408188)
- Vertical supranuclear gaze palsy (HP:0000511): A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal. Evidence: IEA. (OMIM:257220)
- Elevated circulating C-triol concentration (HP:6001353): The concentration of cholestane-3beta, 5alpha, 6beta-triol (C-triol) in the blood circulation is above the upper limit of normal. C-triol is a diagnostic biomarker for Niemann-Pick disease type C. Evidence: PCS. (PMID:34810067)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: IEA. (OMIM:257220)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 3/4. (PMID:12408188)
- CNS foam cells (HP:0003640): The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, in the central nervous system. Evidence: IEA. (OMIM:257220)
- Sea-blue histiocytosis (HP:0001982): An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa. Evidence: PCS. Frequency: 4/4. (PMID:12408188)
- Bone-marrow foam cells (HP:0004333): The presence of foam cells in the bone marrow, generally demonstrated by bone-marrow aspiration or biopsy. Foam cells have a vacuolated appearance due to the presence of complex lipid deposits, giving them a foamy or soap-suds appearance. Evidence: IEA. (OMIM:257220)
- 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: IEA. (OMIM:257220)
- Loss of speech (HP:0002371). Evidence: IEA. (OMIM:257220)
- 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. (PMID:11182931)
- Psychosis (HP:0000709): A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis. Evidence: IEA. (OMIM:257220)
- Dementia (HP:0000726): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: IEA. (OMIM:257220)
- Fatal liver failure in infancy (HP:0006583). Evidence: IEA. (OMIM:257220)
- Neuronal loss in central nervous system (HP:0002529). Evidence: IEA. (OMIM:257220)
- 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:11182931)
- Cataplexy (HP:0002524): A sudden and transient episode of bilateral loss of muscle tone, often triggered by emotions. Evidence: IEA. (OMIM:257220)
- 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: IEA. (OMIM:257220)