- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:470)
- Abnormal renal tubule morphology (HP:0000091): An abnormality of the renal tubules. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Glomerulonephritis (HP:0000099): Inflammation of the renal glomeruli. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Nephrocalcinosis (HP:0000121): Nephrocalcinosis is the deposition of calcium salts in renal parenchyma. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Renal tubular dysfunction (HP:0000124): Abnormal function of the renal tubule. The basic functional unit of the kidney, the nephron, consists of a renal corpuscle attached to a renal tubule, with roughly 0.8 to 1.5 nephrons per adult kidney. The functions of the renal tubule include reabsorption of water, electrolytes, glucose, and amino acids and secretion of substances such as uric acid. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hematuria (HP:0000790): The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- 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: Frequent (HP:0040282). (ORPHA:470)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hepatic failure (HP:0001399). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hepatosplenomegaly (HP:0001433): Simultaneous enlargement of the liver and spleen. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Decreased total leukocyte count (HP:0001882): An abnormal decreased number of leukocytes in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Abnormal bleeding (HP:0001892): An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Respiratory insufficiency (HP:0002093). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hyperglycinemia (HP:0002154): An elevated concentration of glycine in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Steatorrhea (HP:0002570): Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hypercholesterolemia (HP:0003124): An increased concentration of cholesterol in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Elevated circulating LDL-C concentration (HP:0003141): The concentration of low-density lipoprotein cholesterol in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hyperglutaminemia (HP:0003217): The concentration of glutamine in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Decreased circulating HDL-C concentration (HP:0003233): The concentration of high-density lipoprotein cholesterol in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Argininuria (HP:0003268): A increased concentration of arginine in the urine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hyperlysinuria (HP:0003297): An increased concentration of lysine in the urine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hyperalaninemia (HP:0003348): An increased concentration of alanine in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- 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. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Abnormal pulmonary interstitial morphology (HP:0006530): Abnormality of the lung parenchyma extending to the pulmonary interstitium and leading to diffuse pulmonary fibrosis. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hyperprolinemia (HP:0008358): The concentration of proline in the blood circulation is above the upper limit of normal. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Floppy infant (HP:0008947): Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Elevated plasma citrulline (HP:0011966): An increased concentration of citrulline in the blood. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hemophagocytosis (HP:0012156): Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Decreased glomerular filtration rate (HP:0012213): An abnormal reduction in the volume of fluid filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Abnormal circulating serine concentration (HP:0012278): Any deviation from the normal concentration of serine in the blood circulation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Oral aversion (HP:0012523): Reluctance or refusal of a child to be breastfed or eat, manifested as gagging, vomiting, turning head away from food, or avoidance of sensation in or around the mouth (i.e. toothbrushing or face-washing). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Chronic kidney disease (HP:0012622): Functional anomaly of the kidney persisting for at least three months. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Increased circulating lactate dehydrogenase concentration (HP:0025435): An elevated level of the enzyme lactate dehydrogenase in the blood circulation. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Bone marrow hypercellularity (HP:0031020): A larger than normal amount or percentage of hematopoietic cells relative to marrow fat. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:470)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Pancreatitis (HP:0001733): The presence of inflammation in the pancreas. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Renal amyloidosis (HP:0001917): A form of amyloidosis that affects the kidney. On hematoxylin and eosin stain, amyloid is identified as extracellular amorphous material that is lightly eosinophilic. These deposits often stain weakly for periodic acid Schiff (PAS), demonstrate a blue-to-gray hue on the trichrome stain and are typically negative on the Jones methenamine silver (JMS) stain. These tinctorial properties contrast with the histologic appearance of collagen, a major component of basement membranes, mesangial matrix and areas of sclerosis, which demonstrates strong positivity for PAS and JMS (See Figure 1 of PMID:25852856). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Renal tubular acidosis (HP:0001947): Acidosis owing to malfunction of the kidney tubules with accumulation of metabolic acids and hyperchloremia, potentially leading to complications including hypokalemia, hypercalcinuria, nephrolithiasis and nephrocalcinosis. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Tubulointerstitial nephritis (HP:0001970): A form of inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Pulmonary fibrosis (HP:0002206): Replacement of normal lung tissues by fibroblasts and collagen. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Oroticaciduria (HP:0003218): An increased concentration of orotic acid in the urine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Increased circulating ferritin concentration (HP:0003281): Increased concentration of ferritin in the blood circulation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Ornithinuria (HP:0003532): Level of ornithine in the urine above the upper limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Abnormality of humoral immunity (HP:0005368): An abnormality of the humoral immune system, which comprises antibodies produced by B cells as well as the complement system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Megakaryocytopenia (HP:0005548): A reduced count of megakaryocytes. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Abnormal circulating immunoglobulin concentration (HP:0010701): An abnormal deviation from normal levels of immunoglobulins in blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Increased serum zinc (HP:0011424): An increased concentration of zinc in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Hypofibrinogenemia (HP:0011900): Decreased concentration of fibrinogen in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Hepatic amyloidosis (HP:0012280): A form of amyloidosis that affects the liver. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Membranous nephropathy (HP:0012578): A type of glomerulonephropathy characterized by thickening of the basement membrane and deposition of immune complexes in the subepithelial space. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Anti-dsDNA antibody positivity (HP:0020151): The presence of autoantibodies (immunoglobulins) in the serum that react against double-stranded DNA. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Renal fibrosis (HP:0030760): Renal fibrosis is the consequence of an excessive accumulation of extracellular matrix that occurs in virtually every type of chronic kidney disease. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:470)
- Decreased response to growth hormone stimulation test (HP:0000824): Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
- Recurrent bacterial infections (HP:0002718): Increased susceptibility to bacterial infections as manifested by recurrent episodes of bacterial infection. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
- Pathologic fracture (HP:0002756): A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
- Antinuclear antibody positivity (HP:0003493): The presence of autoantibodies in the serum that react against nuclei or nuclear components. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
- Decreased circulating immunoglobulin concentration (HP:0004313): An abnormally decreased level of immunoglobulin in blood. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
- Reduced circulating complement concentration (HP:0004431): An immunodeficiency defined by the absent or suboptimal functioning of one of the complement system proteins. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
- Increased circulating immunoglobulin concentration (HP:0010702): An increased level of gamma globulin (immunoglobulin) in the blood. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:470)
These phenotypes are associated with the disease Lysinuric protein intolerance (ORPHA:470).