- Cyanosis (HP:0000961): Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:621)
- Methemoglobinemia (HP:0012119): Abnormally increased levels of methemoglobin in the blood. In this form of hemoglobin, there is an oxidized ferric iron (Fe +3) rather than the reduced ferrous form (Fe 2+) that is normally found in hemoglobin. Methemoglobin has a reduced affinity for oxygen, resulting in a reduced ability to release oxygen to tissues. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:621)
- Abnormality of the nervous system (HP:0000707): An abnormality of the nervous system. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:621)
- Abnormal nail morphology (HP:0001597): Abnormal structure or appearance of the nail. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:621)
- Exertional dyspnea (HP:0002875): Perceived difficulty to breathe that occurs with exercise or exertion and improves with rest. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:621)
- Lip discoloration (HP:0025118): Lightening or darkening of the lips from their usual coloring. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:621)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Blue sclerae (HP:0000592): An abnormal bluish coloration of the sclera. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- 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: Occasional (HP:0040283). (ORPHA:621)
- 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: Occasional (HP:0040283). (ORPHA:621)
- Global brain atrophy (HP:0002283): Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- 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:621)
- Limb dystonia (HP:0002451): A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Cerebral hypomyelination (HP:0006808): Reduced amount of myelin in the nervous system resulting from defective myelinogenesis in the white matter of the central nervous system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Frontal cortical atrophy (HP:0006913): Atrophy of the frontal cortex. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Temporal cortical atrophy (HP:0007112): Atrophy of the temporal cortex. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Severe intellectual disability (HP:0010864): Severe intellectual disability (ID) is defined as a type of ID characterized by severely sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 20-34. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- Severe global developmental delay (HP:0011344): A severe delay in the achievement of motor or mental milestones in the domains of development of a child. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:621)
- 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: Very rare (HP:0040284). (ORPHA:621)
- Hypertonia (HP:0001276): A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:621)
- 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: Very rare (HP:0040284). (ORPHA:621)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:621)
- Small basal ganglia (HP:0012697): Decreased size of the basal ganglia. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:621)
These phenotypes are associated with the disease Autosomal recessive methemoglobinemia (ORPHA:621).