Phenotypes associated with the disease mitochondrial DNA depletion syndrome 4a (OMIM:203700):
- 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: PCS. Frequency: 1/3. (PMID:15122711)
- 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: IEA. (OMIM:203700)
- 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:15122711)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:203700)
- Paralysis (HP:0003470): Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Motor paralysis results from deficits of the upper motor neurons (corticospinal, corticobulbar, or subcorticospinal). Motor paralysis is often accompanied by an impairment in the facility of movement. Evidence: IEA. (OMIM:203700)
- Bile duct proliferation (HP:0001408): Proliferative changes of the bile ducts. Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- Tracheomalacia (HP:0002779). Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Aciduria (HP:0012072): Excretion of urine with an acid pH, i.e., having an increased hydrogen ion concentration. Evidence: TAS. (OMIM:203700)
- Acute hepatic failure (HP:0006554): Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as acute if there is onset of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver. Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Visual loss (HP:0000572): Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that). Evidence: IEA. (OMIM:203700)
- Ascites (HP:0001541): Accumulation of fluid in the peritoneal cavity (between the layers of the peritoneum that lines the abdomen). Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- Hypoventilation (HP:0002791): A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide). Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- 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:203700)
- 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: 1/3. (PMID:15122711)
- Tetraparesis (HP:0002273): Weakness of all four limbs. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Vegetative state (HP:0031358): The absence of wakefulness and consciousness, but in contrast to a coma, there is involuntary opening of the eyes and movements such as teeth grinding, yawning, or thrashing of the extremities. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Abnormality of visual evoked potentials (HP:0000649): An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex. Evidence: IEA. (OMIM:203700)
- Dementia (HP:0000726): A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. Evidence: IEA. (OMIM:203700)
- 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:15122711)
- Microvesicular hepatic steatosis (HP:0001414): A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes. Evidence: IEA. (OMIM:203700)
- Micronodular cirrhosis (HP:0001413): A type of cirrhosis characterized by the presence of small regenerative nodules. Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- Myoclonus (HP:0001336): Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements. Evidence: IEA. (OMIM:203700)
- Rapidly progressive (HP:0003678): Applies to a disease manifestation that quickly increases in scope or severity over the course of time. Evidence: PCS. (PMID:15122711)
- 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: 1/3. (PMID:15122711)
- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- 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: PCS. Frequency: 2/3. (PMID:15122711)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. (OMIM:203700)
- Epilepsia partialis continua (HP:0012847): Epilepsia partialis continua (also called Kojevnikov's or Kozhevnikov's epilepsia) is a type of focal motor status epilepticus characterized by repeated stereotyped simple motor manifestations such as jerks, typically of a limb or the face, recurring every few seconds or minutes for extended periods (days or years). Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- 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: 1/3. (PMID:15122711)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:203700)
- Cerebral visual impairment (HP:0100704): A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. Evidence: PCS. Frequency: 3/3. (PMID:15122711)
- Focal myoclonic seizure (HP:0011166): A type of focal motor seizure characterized by sudden, brief (<100 ms) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Anasarca (HP:0012050): An extreme form of generalized edema with widespread and massive edema due to effusion of fluid into the extracellular space. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. Frequency: 3/3. (PMID:15122711)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- 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: PCS. Frequency: 1/3. (PMID:15122711)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. (OMIM:203700)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: IEA. (OMIM:203700)
- Generalized non-convulsive status epilepticus without coma (HP:0032860): Generalized non-convulsive status epilepticus without coma is a type of status epilepticus without prominent motor signs, which is electrographically generalized. It is a prolonged absence seizure. Evidence: PCS. Frequency: 1/3. (PMID:15122711)
- Gliosis (HP:0002171): Gliosis is the focal proliferation of glial cells in the central nervous system. Evidence: PCS. Frequency: 2/3. (PMID:15122711)
- Neuronal loss in central nervous system (HP:0002529). Evidence: IEA. (OMIM:203700)
- Ethylmalonic aciduria (HP:0003219): The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: TAS. (OMIM:203700)
- Increased CSF protein concentration (HP:0002922): Increased concentration of protein in the cerebrospinal fluid. Evidence: IEA. (OMIM:203700)
- Cerebral cortical neurodegeneration (HP:0006964). Evidence: IEA. (OMIM:203700)
- 3-Methylglutaconic aciduria (HP:0003535): An increased amount of 3-methylglutaconic acid in the urine. Evidence: TAS. (OMIM:203700)
- Astrocytosis (HP:0002446): Proliferation of astrocytes in the area of a lesion of the central nervous system. Evidence: IEA. (OMIM:203700)