- 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: PCS. Frequency: 1/7. (PMID:30715177)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 7/7. (PMID:30715177)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: PCS. Frequency: 1/1. (PMID:25330800)
- Hypochromic microcytic anemia (HP:0004840): A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- 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: 7/7. (PMID:30715177)
- Renal insufficiency (HP:0000083): A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. Evidence: PCS. Frequency: 2/7. (PMID:30715177)
- Narrow mouth (HP:0000160): Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective). Evidence: PCS. Frequency: 1/1. (PMID:25330800)
- 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: PCS. Frequency: 6/8. (PMID:25330800;PMID:30715177)
- Mild proteinuria (HP:0012595): Mildly increased levels of protein in the urine (150-500 mg per day in adults). Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 6/6. (PMID:30715177)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:25330800)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 3/7. (PMID:30715177)
- Decreased activity of mitochondrial respiratory chain (HP:0008972): Decreased activity of the mitochondrial respiratory chain. Evidence: IEA. Frequency: 1/1. (PMID:25330800)
- Ketosis (HP:0001946): Presence of elevated levels of ketone bodies in the body. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Cerebral calcification (HP:0002514): The presence of calcium deposition within the cerebrum. Evidence: PCS. Frequency: 8/8. (PMID:30715177;PMID:21427441)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Spastic tetraplegia (HP:0002510): Spastic paralysis affecting all four limbs. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: PCS. Frequency: 6/7. (PMID:30715177)
- Increased circulating pyruvate concentration (HP:0003542): The concentration of pyruvate in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/7. (PMID:30715177)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 5/5. (PMID:30715177)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 7/7. (PMID:30715177)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 1/1. (PMID:25330800)
- 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: PCS. Frequency: 1/1. (PMID:21427441)
- Leukoencephalopathy (HP:0002352): This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Increased circulating lactate concentration (HP:0002151): Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35). Evidence: PCS. Frequency: 4/8. (PMID:25330800;PMID:30715177)
- 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. Frequency: 2/2. (PMID:25330800;PMID:21427441)
- Generalized tonic seizure (HP:0010818): A generalized tonic seizure is a type of generalized motor seizure characterized by bilateral limb stiffening or elevation, often with neck stiffening without a subsequent clonic phase. The tonic activity can be a sustained abnormal posture, either in extension or flexion, sometimes accompanied by tremor of the extremities. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- 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: PCS. Frequency: 7/7. (PMID:30715177)
- Death in childhood (HP:0003819): Death in during childhood, defined here as between the ages of 2 and 10 years. Evidence: PCS. Frequency: 2/7. (PMID:30715177)
- 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: PCS. Frequency: 1/1. (PMID:25330800)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. Frequency: 2/2. (PMID:25330800;PMID:21427441)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 1/1. (PMID:25330800)
- Decreased CSF biopterin level (HP:0040209): Concentration of biopterin in the cerebrospinal fluid (CSF) below the lower limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- 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:21427441)
- Akinesia (HP:0002304): Inability to initiate changes in activity or movement and to perform ordinary volitional movements rapidly and easily. Evidence: PCS. Frequency: 1/1. (PMID:21427441)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 1/1. (PMID:25330800)
- Congenital sensorineural hearing impairment (HP:0008527): A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset. Evidence: PCS. Frequency: 7/7. Onset: Congenital onset (HP:0003577). (PMID:30715177)
These phenotypes are associated with the disease leukoencephalopathy, progressive, infantile-onset, with or without deafness (OMIM:619147).