- Hypermethioninemia (HP:0003235): An increased concentration of methionine in the blood. Evidence: PCS. Frequency: 13/13. (PMID:20301697;PMID:26667307)
- Lens subluxation (HP:0001132): Partial dislocation of the lens of the eye. Evidence: PCS. Frequency: 13/19. (PMID:9775245)
- Stroke (HP:0001297): Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain. Evidence: IEA. (OMIM:236200)
- Limitation of joint mobility (HP:0001376): A reduction in the freedom of movement of one or more joints. Evidence: IEA. (OMIM:236200)
- 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: IEA. (OMIM:236200)
- Hypopigmentation of the skin (HP:0001010): A reduction of skin color related to a decrease in melanin production and deposition. Evidence: TAS. (OMIM:236200)
- 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: 3/3. (PMID:26667307)
- Reduced cystathionine beta-synthase activity in cultured fibroblasts (HP:6000357): Activity of cystathionine beta-synthase (EC 4.2.1.22) below the lower limit of normal in cultured fibroblasts. Evidence: PCS. (PMID:5647845)
- Depression (HP:0000716): Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior. Evidence: TAS. (OMIM:236200)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 4/23. (PMID:11596648)
- Personality disorder (HP:0012075): A personality disorder is a deeply ingrained pattern of behavior of a specified kind that deviates markedly from the norms of generally accepted behavior. It is typically apparent by the time of adolescence and causes long-term difficulties in personal relationships or functioning in society. Evidence: TAS. (OMIM:236200)
- Dental crowding (HP:0000678): Changes in alignment of teeth in the dental arch. Evidence: IEA. (OMIM:236200)
- 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: 14/14. (PMID:20301697;PMID:8755636;PMID:26667307)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 19/23. (PMID:11596648)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: PCS. Frequency: 2/3. (PMID:26667307)
- Tall stature (HP:0000098): A height above that which is expected according to age and gender norms. Evidence: TAS. (OMIM:236200)
- Homocystinuria (HP:0002156): An increased concentration of homocystine in the urine. Evidence: IEA. (OMIM:236200)
- 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: 3/3. (PMID:26667307)
- 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: IEA. (PMID:20301697)
- Flushing (HP:0031284): Recurrent episodes of redness of the skin together with a sensation of warmth or burning of the affected areas of skin. Evidence: PCS. Frequency: 3/3. (PMID:26667307)
- Cutis marmorata (HP:0000965): A reticular discoloration of the skin with cyanotic (reddish-blue appearing) areas surrounding pale central areas due to dilation of capillary blood vessels and stagnation of blood within the vessels. Cutis marmorata generally occurs on the legs, arms and trunk and is often more severe in cold weather. Evidence: TAS. (OMIM:236200)
- Myocardial infarction (HP:0001658): Necrosis of the myocardium caused by an obstruction of the blood supply to the heart and often associated with chest pain, shortness of breath, palpitations, and anxiety as well as characteristic EKG findings and elevation of serum markers including creatine kinase-MB fraction and troponin. Evidence: IEA. (OMIM:236200)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. (PMID:20301697)
- 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:20301697)
- Pectus carinatum (HP:0000768): A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum. Evidence: PCS. Frequency: 1/3. (PMID:26667307)
- Pancreatitis (HP:0001733): The presence of inflammation in the pancreas. Evidence: IEA. (OMIM:236200)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: TAS. (OMIM:236200)
- Retinal detachment (HP:0000541): Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Evidence: PCS. Frequency: 1/3. (PMID:26667307)
- Biconcave vertebral bodies (HP:0004586): Exaggerated concavity of the anterior or posterior surface of the vertebral body, i.e., the upper and lower vertebral endplates are hollowed inward. Evidence: TAS. (OMIM:236200)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: IEA. (OMIM:236200)
- Hyperhomocystinemia (HP:0002160): An increased concentration of homocystine in the blood. Evidence: PCS. Frequency: 14/14. (PMID:20301697;PMID:8755636;PMID:26667307)
- Generalized osteoporosis (HP:0040160). Evidence: TAS. (OMIM:236200)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 3/3. (PMID:26667307)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: PCS. Frequency: 0/1. (PMID:8755636)
- Thromboembolism (HP:0001907): The formation of a blood clot inside a blood vessel that subsequently travels through the blood stream from the site where it formed to another location in the body, generally leading to vascular occlusion at the distant site. Evidence: PCS. (PMID:20301697)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:236200)
- Unsteady gait (HP:0002317). Evidence: PCS. Frequency: 3/3. (PMID:26667307)
- 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: IEA. (OMIM:236200)
- Exotropia (HP:0000577): A form of strabismus with one or both eyes deviated outward. Evidence: PCS. Frequency: 3/3. (PMID:26667307)
- Arachnodactyly (HP:0001166): Abnormally long and slender fingers (spider fingers). Evidence: PCS. Frequency: 3/4. (PMID:8755636;PMID:26667307)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 4/4. (PMID:8755636;PMID:26667307)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. (PMID:20301697)
- Brittle hair (HP:0002299): Fragile, easily breakable hair, i.e., with reduced tensile strength. Evidence: IEA. (OMIM:236200)
- Ectopia lentis (HP:0001083): Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation. Evidence: PCS. Frequency: 18/37. (PMID:8755636;PMID:26667307;PMID:9775245;PMID:11641642)
- 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: IEA. (OMIM:236200)
- Disproportionate tall stature (HP:0001519): A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim. Evidence: PCS. Frequency: 11/11. (PMID:20301697;PMID:8755636)
- Methioninuria (HP:0032352): Level of methionine in urine above the upper limit of normal. Evidence: IEA. (OMIM:236200)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. Frequency: 4/19. (PMID:9775245)
- Glaucoma (HP:0000501): Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure. Evidence: IEA. (OMIM:236200)
- Mitral valve prolapse (HP:0001634): One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle. Evidence: IEA. (OMIM:236200)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: PCS. Frequency: 11/22. (PMID:26667307;PMID:9775245)
These phenotypes are associated with the disease classic homocystinuria (OMIM:236200).