- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 2/2. (PMID:22069215)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: IEA. (OMIM:606812)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: IEA. (OMIM:606812)
- Hypoplasia of the brainstem (HP:0002365): Underdevelopment of the brainstem. Evidence: TAS. (OMIM:606812)
- Mitochondrial swelling (HP:0030774): The mitochondrial matrix refers to the substance occupying the space enclosed by the inner membrane of a mitochondrion, which contains enzymes, DNA, granules, and inclusions of protein crystals, glycogen, and lipid. Mitochondrial swelling refers to an increase in size of the mitochondrial matrix. This phenomenon is thought to be related to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix. Mitochondrial swelling may distend the outer membrane until it ruptures. Evidence: PCS. Frequency: 1/1. (PMID:22069215)
- Abnormal speech pattern (HP:0002167): An abnormality in the sound (volume) or cadence (rate) of speech. Evidence: IEA. (OMIM:606812)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: IEA. (OMIM:606812)
- 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: IEA. (OMIM:606812)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: PCS. Frequency: 2/2. (PMID:22069215)
- 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: 1/2. (PMID:22069215)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:606812)
- Relative macrocephaly (HP:0004482): A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account. Evidence: IEA. (OMIM:606812)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:606812)
- Perimembranous ventricular septal defect (HP:0011682): A ventricular septal defect that is confluent with and involves the membranous septum and is bordered by an atrioventricular valve, not including the type 3 VSDs. Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: IEA. (OMIM:606812)
- Cutaneous leiomyoma (HP:0007620): The presence of leiomyoma of the skin. Evidence: IEA. (OMIM:606812)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 2/2. (PMID:22069215)
- 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:606812)
- Intrahepatic cholestasis (HP:0001406): Impairment of bile flow due to obstruction in the small bile ducts within the liver. Evidence: PCS. Frequency: 2/2. (PMID:22069215)
- Polycythemia (HP:0001901): Polycythemia is diagnosed if the red blood cell count, the hemoglobin level, and the red blood cell volume all exceed the upper limits of normal. Evidence: TAS. (OMIM:606812)
- Metabolic acidosis (HP:0001942): Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause. Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- Increased urine succinate level (HP:0033092): The concentration of succinate in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:22069215)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: IEA. (OMIM:606812)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: IEA. (OMIM:606812)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: IEA. (OMIM:606812)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 2/2. (PMID:22069215)
- Status epilepticus (HP:0002133): Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. Evidence: IEA. (OMIM:606812)
- Ascites (HP:0001541): Accumulation of fluid in the peritoneal cavity (between the layers of the peritoneum that lines the abdomen). Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- 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. (OMIM:606812)
- Choroid plexus cyst (HP:0002190): A cyst occurring within the choroid plexus within a cerebral ventricle. Evidence: TAS. (OMIM:606812)
- Conjunctival icterus (HP:0032106): Conjunctival icterus is a condition where there is yellowing of the whites of the eyes. This is most commonly seen in patients who have liver disease. Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: IEA. (OMIM:606812)
- Bilateral fetal pyelectasis (HP:0011129): A bilateral form of fetal pyelectasis. Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- Elevated urine fumaric acid level (HP:0034648): The concentration of fumaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:22069215)
- Necrotizing enterocolitis (HP:0033165): Inflammation of the intestine leading to bacterial invasion causing cellular damage and death which causes necrosis of the colon and intestine. Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- Second trimester onset (HP:0034198): This term refers to a phenotypic feature that was first observed prior to birth during the second trimester, which comprises the range of gestational ages from 14 0/7 weeks to 27 6/7 (inclusive). Evidence: PCS. Frequency: 2/2. (PMID:22069215)
- Hyperbilirubinemia (HP:0002904): An increased amount of bilirubin in the blood. Evidence: IEA. (OMIM:606812)
- Open operculum (HP:0100954): Underdevelopment of the operculum. Evidence: TAS. (OMIM:606812)
- Lissencephaly (HP:0001339): A spectrum of malformations of cortical development caused by insufficient neuronal migration that subsumes the terms agyria, pachygyria and subcortical band heterotopia. See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly. Evidence: PCS. Frequency: 1/2. (PMID:22069215)
- 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:22069215)
- 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: IEA. (OMIM:606812)
- Reduced subcutaneous adipose tissue (HP:0003758): A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness. Evidence: IEA. (OMIM:606812)
- 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: IEA. (OMIM:606812)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: IEA. (OMIM:606812)
- Decreased fumarate hydratase activity (HP:0003536): An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of fumarate hydratase activity. Evidence: PCS. Frequency: 1/1. (PMID:22069215)
- Polymicrogyria (HP:0002126): Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds). Evidence: IEA. (OMIM:606812)
These phenotypes are associated with the disease fumaric aciduria (OMIM:606812).