Phenotypes associated with the disease tyrosinemia type I (OMIM:276700):
- Nephrocalcinosis (HP:0000121): Nephrocalcinosis is the deposition of calcium salts in renal parenchyma. Evidence: IEA. (OMIM:276700)
- Hypermethioninemia (HP:0003235): An increased concentration of methionine in the blood. Evidence: IEA. (OMIM:276700)
- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 18/18. (PMID:33046095)
- Hypertyrosinemia (HP:0003231): An increased concentration of tyrosine in the blood. Evidence: PCS. (PMID:33046095)
- 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: IEA. (OMIM:276700)
- Episodic peripheral neuropathy (HP:0006949). Evidence: IEA. (OMIM:276700)
- Elevated urinary succinylacetone level (HP:6000598): Presence in the urine of succinylacetone, which is one of the toic block metabolites formed in tyrosinaemia type 1 because of a defect in the final enzyme of the pathway of the degradation of tyrosine, namely fumarylacetoacetase (FAH, EC 3.7.1.2). Evidence: PCS. (PMID:23311542)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 10/17. (PMID:33046095)
- Cirrhosis (HP:0001394): A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function. Evidence: IEA. (OMIM:276700)
- Elevated urinary 4-tyramine level (HP:6000775): The amount of 4-tyramine in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: PCS. (PMID:20301688)
- Prolonged prothrombin time (HP:0008151): Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT. Evidence: TAS. (OMIM:276700)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: IEA. (OMIM:276700)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 8/18. (PMID:33046095)
- Elevated circulating alpha-fetoprotein concentration (HP:0006254): The concentration of alpha-fetoprotein in the blood circulation is above the upper limit of normal. Evidence: IEA. (OMIM:276700)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 9/18. (PMID:33046095)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: PCS. Frequency: 9/18. (PMID:33046095)
- 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: IEA. (OMIM:276700)
- Hypophosphatemic rickets (HP:0004912). Evidence: IEA. (OMIM:276700)
- Periodic paralysis (HP:0003768): Episodes of muscle weakness. Evidence: IEA. (OMIM:276700)
- Gastrointestinal hemorrhage (HP:0002239): Hemorrhage affecting the gastrointestinal tract. Evidence: TAS. (OMIM:276700)
- 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: IEA. (OMIM:276700)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 6/17. (PMID:33046095)
- 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: 12/18. (PMID:33046095)
- Hepatocellular carcinoma (HP:0001402): A kind of neoplasm of the liver that originates in hepatocytes and presents macroscopically as a soft and hemorrhagic tan mass in the liver. Evidence: IEA. (OMIM:276700)
- Prolonged partial thromboplastin time (HP:0003645): Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms. Evidence: TAS. (OMIM:276700)
- Pancreatic islet-cell hyperplasia (HP:0004510): Hyperplasia of the islets of Langerhans, i.e., of the regions of the pancreas that contain its endocrine cells. Evidence: IEA. (OMIM:276700)
- Ascites (HP:0001541): Accumulation of fluid in the peritoneal cavity (between the layers of the peritoneum that lines the abdomen). Evidence: PCS. Frequency: 9/18. (PMID:33046095)
- Episodic vomiting (HP:0002572): Paroxysmal, recurrent episodes of vomiting. Evidence: PCS. Frequency: 7/18. (PMID:33046095)
- Elevated urinary delta-aminolevulinic acid (HP:0003163): An increased concentration of 5-aminolevulinic acid (CHEBI:17549) in the urine. Evidence: IEA. (OMIM:276700)
- Elevated circulating succinylacetone concentration (HP:6001410): The concentration of succinylacetone in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:32832707)
- Glomerular sclerosis (HP:0000096): Accumulation of scar tissue within the glomerulus. Evidence: IEA. (OMIM:276700)
- Paralytic ileus (HP:0002590). Evidence: IEA. (OMIM:276700)
- Diminished tissue fumarylacetoacetate hydrolase activity (HP:6000827): Concentration or activity of fumarylacetoacetate hydrolase (FAH; EC 3.7.1.2) below the lower limit of normal. This enzyme can be measured in multiple tissues including leukocytes and cultured fibroblasts. Evidence: PCS. Frequency: 9/9. (PMID:6622096)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: IEA. (OMIM:276700)
- 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:8028615)
- Melena (HP:0002249): The passage of blackish, tarry feces associated with gastrointestinal hemorrhage. Melena occurs if the blood remains in the colon long enough for it to be broken down by colonic bacteria. One degradation product, hematin, imbues the stool with a blackish color. Thus, melena generally occurs with bleeding from the upper gastrointestinal tract (e.g., stomach ulcers or duodenal ulcers), since the blood usually remains in the gut for a longer period of time than with lower gastrointestinal bleeding. Evidence: PCS. Frequency: 5/18. (PMID:33046095)
- Renal Fanconi syndrome (HP:0001994): An inability of the tubules in the kidney to reabsorb small molecules, causing increased urinary loss of electrolytes (sodium, potassium, bicarbonate), minerals, glucose, amino acids, and water. Evidence: IEA. (OMIM:276700)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 12/18. (PMID:33046095)
- Enlarged kidney (HP:0000105): An abnormal increase in the size of the kidney. Evidence: PCS. Frequency: 10/17. (PMID:33046095)