Phenotypes associated with the disease 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (OMIM:614739):
- Encephalopathy (HP:0001298): Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state. Evidence: TAS. (OMIM:614739)
- Inability to walk (HP:0002540): Incapability to ambulate. Evidence: IEA. (OMIM:614739)
- Abnormality of the coagulation cascade (HP:0003256): An abnormality of the coagulation cascade, which is comprised of the contact activation pathway (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway) as well as cofactors and regulators. Evidence: TAS. (OMIM:614739)
- 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: PCS. Frequency: 14/14. (PMID:22683713)
- 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. (OMIM:614739)
- 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: Occasional (HP:0040283). (OMIM:614739)
- 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: TAS. (OMIM:614739)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:614739)
- Brain atrophy (HP:0012444): Partial or complete wasting (loss) of brain tissue that was once present. Evidence: PCS. Frequency: 8/11. (PMID:22683713)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. (OMIM:614739)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: TAS. (OMIM:614739)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: TAS. (OMIM:614739)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: TAS. (OMIM:614739)
- Aplasia/Hypoplasia involving the central nervous system (HP:0002977): Absence or underdevelopment of tissue in the central nervous system. Evidence: TAS. (OMIM:614739)
- 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: TAS. Frequency: 14/14. (OMIM:614739)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: TAS. (OMIM:614739)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: PCS. Frequency: 8/13. (PMID:22683713)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:614739)
- Absent speech (HP:0001344): Complete lack of development of speech and language abilities. Evidence: IEA. (OMIM:614739)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 15/15. (PMID:22683713)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. (OMIM:614739)
- 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: 14/14. (PMID:22683713)
- 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: TAS. Frequency: 14/15. (OMIM:614739)
- Putaminal eye sign (HP:6001454): An imaging anomly of the putamen that is thought to be pathognomic for MEGDEL syndrome (3-MethylGlutaconic aciduria, Deafness, Encephalopathy, Leigh-like syndrome MIM #614739). In stage 1 of the disease, T2 signal changes of the pallidum are present. In stage 2, swelling of the putamen and caudate nucleus is seen. The dorsal putamen contains an eye that shows no signal alteration and (thus) seems to be spared during this stage of the disease. It later increases, reflecting progressive putaminal involvement. Sparing of the mid dorsal putamen (showing normal signal surrounded by T2 hyperintense signal) is referred to as the putaminal eye. Evidence: PCS. Frequency: 30/30. (PMID:25642805)
- Abnormality of extrapyramidal motor function (HP:0002071): A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless). Evidence: TAS. (OMIM:614739)
- Neonatal sepsis (HP:0040187): Systemic inflammatory response to infection in newborn babies. Evidence: TAS. (OMIM:614739)
- 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: 13/14. (PMID:22683713)
- 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:22683713)
- 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:614739)
- 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: PCS. Frequency: 13/14. (PMID:22683713)
- 3-Methylglutaconic aciduria (HP:0003535): An increased amount of 3-methylglutaconic acid in the urine. Evidence: PCS. Frequency: 14/14. (PMID:22683713)