- Stage 5 chronic kidney disease (HP:0003774): A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine. Evidence: TAS. (OMIM:222700)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: TAS. (OMIM:222700)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: TAS. (OMIM:222700)
- Hyperlysinuria (HP:0003297): An increased concentration of lysine in the urine. Evidence: PCS. Frequency: 10/10. (PMID:10080182)
- 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: 4/9. (PMID:10080182)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 8/10. (PMID:10080182)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 10/10. (PMID:10080182)
- Sparse hair (HP:0008070): Reduced density of hairs. Evidence: TAS. (OMIM:222700)
- 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: 5/6. (PMID:10080182)
- Hemophagocytosis (HP:0012156): Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues. Evidence: TAS. (OMIM:222700)
- Hypolysinemia (HP:0500142): The concentration of lysine in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 10/10. (PMID:10080182)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. (PMID:10080182)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: IEA. Frequency: 4/7. (OMIM:222700)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: TAS. (OMIM:222700)
- Recurrent fractures (HP:0002757): The repeated occurrence of bone fractures (implying an abnormally increased tendency for fracture). Evidence: TAS. (OMIM:222700)
- Muscle weakness (HP:0001324): Reduced strength of muscles. Evidence: IEA. (OMIM:222700)
- Nausea (HP:0002018): A sensation of unease in the stomach together with an urge to vomit. Evidence: PCS. (PMID:10080182)
- Hyperextensible skin (HP:0000974): A condition in which the skin can be stretched beyond normal, and then returns to its initial position. Evidence: TAS. (OMIM:222700)
- 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: PCS. Frequency: 2/4. (PMID:10080182)
- Protein avoidance (HP:0002038). Evidence: PCS. Frequency: 9/10. (PMID:10080182)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:222700)
- Cutis laxa (HP:0000973): Wrinkled, redundant, inelastic and sagging skin. Evidence: IEA. (OMIM:222700)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: IEA. (OMIM:222700)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: IEA. (OMIM:222700)
- Fine hair (HP:0002213): Hair that is fine or thin to the touch. Evidence: TAS. (OMIM:222700)
- 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: TAS. (OMIM:222700)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: IEA. (OMIM:222700)
- Decreased total leukocyte count (HP:0001882): An abnormal decreased number of leukocytes in the blood. Evidence: IEA. (OMIM:222700)
- 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. (PMID:10080182)
- 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: 10/10. (PMID:10080182)
- 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: IEA. (OMIM:222700)
- Malnutrition (HP:0004395): A deficiency in the intake of energy and nutrients. Evidence: TAS. (OMIM:222700)
- Increased circulating ferritin concentration (HP:0003281): Increased concentration of ferritin in the blood circulation. Evidence: IEA. (OMIM:222700)
- Respiratory insufficiency (HP:0002093). Evidence: IEA. Frequency: 1/4. (OMIM:222700)
- Pulmonary hemorrhage (HP:0040223): Pulmonary hemorrhage is a bleeding within the lungs. Older children and adults may spit blood or bloody sputum. Neonates, infants and young children usually do not spit up blood. Anemia, pulmonary infiltrates, increasingling bloody return on BAL and the presence of hemosiderin-laden macrophages in broncho-alveolar lavage (BAL) fluid or lung biopsy can diagnose lung bleeding. Alveolar macrophages contain phagocytosed red blood cells and stain positive for hemosiderin, a product of hemoglobin degradation, after about 48-72 hours following pulmonary hemorraghe. Previous or recurrent bleeding can thus be distinguished from fresh events. A differentiation into local or diffuse is of importance. Also differentiate if pulmonary hemorrhage is due to a primary lung disorder or a manifestation of a systemic disease. Evidence: TAS. (OMIM:222700)
- 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:10080182)
- Psychotic episodes (HP:0000725): Periods of time during which an individual experiences significant disturbances in their thoughts, perceptions, emotions, and behavior, resulting in a loss of touch with reality. These episodes are hallmark features of psychotic disorders such as schizophrenia, schizoaffective disorder, and certain forms of bipolar disorder. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:222700)
- Truncal obesity (HP:0001956): Obesity located preferentially in the trunk of the body as opposed to the extremities. Evidence: TAS. (OMIM:222700)
- Oroticaciduria (HP:0003218): An increased concentration of orotic acid in the urine. Evidence: TAS. (OMIM:222700)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: IEA. (OMIM:222700)
- Pancreatitis (HP:0001733): The presence of inflammation in the pancreas. Evidence: IEA. (OMIM:222700)
- Coma (HP:0001259): The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli. Evidence: IEA. (OMIM:222700)
These phenotypes are associated with the disease lysinuric protein intolerance (OMIM:222700).