Phenotypes associated with the disease severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (OMIM:615486):
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: PCS. Frequency: 6/30. (PMID:24103465;PMID:25913036)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: TAS. (OMIM:615486)
- Cholestasis (HP:0001396): Impairment of bile flow due to obstruction in bile ducts. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Thrombocytosis (HP:0001894): Increased numbers of platelets in the peripheral blood. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Hepatic failure (HP:0001399). Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- 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: 1/1. (PMID:24103465)
- Hepatic fibrosis (HP:0001395): The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process. Evidence: PCS. Frequency: 1/29. (PMID:25913036)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 26/29. (PMID:25913036)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 25/29. (PMID:25913036)
- 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: PCS. Frequency: 8/29. (PMID:25913036)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 13/29. (PMID:25913036)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 23/30. (PMID:24103465;PMID:25913036)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 3/29. (PMID:25913036)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Abnormal pulmonary interstitial morphology (HP:0006530): Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Neonatal onset (HP:0003623): Onset of signs or symptoms of disease within the first 28 days of life. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Lactic acidosis (HP:0003128): An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 19/29. (PMID:25913036)
- Intraalveolar phospholipid accumulation (HP:0006517): Accumulation of amorphous PAS-positive material in the space between alveolar macrophages, sometimes as condensed form (oval bodies) are typically found in alveolar proteinosis. Evidence: PCS. (PMID:25913036)
- 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:24103465)
- Dyspnea (HP:0002094): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: PCS. Frequency: 28/29. (PMID:25913036)
- Cough (HP:0012735): A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. Evidence: PCS. Frequency: 7/29. (PMID:25913036)
- Elevated gamma-glutamyltransferase level (HP:0030948): Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues. Evidence: PCS. Frequency: 20/29. (PMID:25913036)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. (PMID:25913036)
- Hypoxemia (HP:0012418): An abnormally low level of blood oxygen. Evidence: PCS. Frequency: 14/29. (PMID:25913036)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 1/1. (PMID:24103465)
- Clubbing (HP:0001217): Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails. Evidence: PCS. Frequency: 8/29. (PMID:25913036)
- 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:24103465)
- Pulmonary fibrosis (HP:0002206): Replacement of normal lung tissues by fibroblasts and collagen. Evidence: PCS. Frequency: 12/18. (PMID:25913036)