- Progressive neurologic deterioration (HP:0002344). Evidence: TAS. (OMIM:219800)
- Failure to thrive in infancy (HP:0001531). Evidence: PCS. Frequency: 2/2. Onset: Infantile onset (HP:0003593). (PMID:35513889)
- Elevated leukocyte cystine (HP:0032639): An increased concentration of cystine within white blood cells. Evidence: PCS. Frequency: 15/15. (PMID:24464559)
- 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: PCS. Frequency: 15/15. Onset: Infantile onset (HP:0003593). (PMID:24464559)
- Decreased circulating carnitine concentration (HP:0003234): Concentration of carnitine in the blood circulation below the lower limit of normal. Evidence: TAS. (OMIM:219800)
- Aminoaciduria (HP:0003355): An increased concentration of an amino acid in the urine. Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- Myopathy (HP:0003198): A disorder of muscle unrelated to impairment of innervation or neuromuscular junction. Evidence: PCS. Frequency: 22/86. Onset: Young adult onset (HP:0011462). (PMID:21900880)
- 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: PCS. Frequency: 28/38. (PMID:20803298;PMID:24464559)
- Hypopigmentation of the skin (HP:0001010): A reduction of skin color related to a decrease in melanin production and deposition. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 18/18. (PMID:35513889;PMID:24464559;PMID:31672123)
- Glycosuria (HP:0003076): An increased concentration of glucose in the urine. Evidence: PCS. Frequency: 3/3. (PMID:35513889;PMID:31672123)
- Primary hypothyroidism (HP:0000832): A type of hypothyroidism that results from a defect in the thyroid gland. Evidence: PCS. Frequency: 4/15. Onset: Childhood onset (HP:0011463). (PMID:24464559)
- Hyperphosphaturia (HP:0003109): An increased excretion of phosphates in the urine. Evidence: PCS. Frequency: 3/3. (PMID:35513889;PMID:31672123)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: IEA. (OMIM:219800)
- Hypophosphatemic rickets (HP:0004912). Evidence: PCS. Frequency: 2/3. (PMID:35513889;PMID:31672123)
- Episodic metabolic acidosis (HP:0004911): Repeated transient episodes of metabolic acidosis, that is, of the buildup of acid or depletion of base due to accumulation of metabolic acids. Evidence: IEA. (OMIM:219800)
- 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: 0/17. (PMID:32102670)
- Skeletal muscle atrophy (HP:0003202): The presence of skeletal muscular atrophy (which is also known as amyotrophy). Evidence: IEA. (OMIM:219800)
- Recurrent corneal erosions (HP:0000495): The presence of recurrent corneal epithelial erosions. Although most corneal epithelial defects heal quickly, some may show recurrent ulcerations. Evidence: IEA. (OMIM:219800)
- Low-molecular-weight proteinuria (HP:0003126): Excretion in urine of proteins of a size smaller than albumin (molecular weight 69 kD). Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- 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:219800)
- 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: 1/1. (PMID:31672123)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- Generalized aminoaciduria (HP:0002909): An increased concentration of all types of amino acid in the urine. Evidence: IEA. (OMIM:219800)
- Microscopic hematuria (HP:0002907): Microscopic hematuria detected by dipstick or microscopic examination of the urine. Evidence: IEA. (OMIM:219800)
- Exocrine pancreatic insufficiency (HP:0001738): Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes. Evidence: IEA. (OMIM:219800)
- Rickets (HP:0002748): Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets. Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- Rickets (HP:0002748): Rickets is divided into two major categories including calcipenic and phosphopenic. Hypophosphatemia is described as a common manifestation of both categories. Hypophosphatemic rickets is the most common type of rickets that is characterized by low levels of serum phosphate, resistance to ultraviolet radiation or vitamin D intake. There are several issues involved in hypophosphatemic rickets such as calcium, vitamin D, phosphorus deficiencies. Moreover, other disorder can be associated with its occurrence such as absorption defects due to pancreatic, intestinal, gastric, and renal disorders and hepatobiliary disease. Symptoms are usually seen in childhood and can be varied in severity. Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is the most common type of rickets. Evidence: PCS. Frequency: 13/15. Onset: Infantile onset (HP:0003593). (PMID:24464559)
- Hyponatremia (HP:0002902): The concentration of sodium in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- 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:12110740)
- Hypokalemia (HP:0002900): The concentration of potassium(1+) in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 3/3. (PMID:35513889;PMID:31672123)
- Hypohidrosis (HP:0000966): Abnormally diminished capacity to sweat. Evidence: IEA. (OMIM:219800)
- Retinopathy (HP:0000488): Any noninflammatory disease of the retina. This nonspecific term is retained here because of its wide use in the literature, but if possible new annotations should indicate the precise type of retinal abnormality. Evidence: IEA. (OMIM:219800)
- Hypophosphatemia (HP:0002148): The concentration of phosphate ion in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- Elevated intracellular cystine (HP:0003358): An increased concentration of cystine within cells. This finding can be demonstrated on leukocytes, but is not specific to blood cells. Evidence: IEA. (OMIM:219800)
- Oral motor hypotonia (HP:0030190): Reduced muscle tone of oral musculature. In infants, this feature may be associated with difficulties in breast feeding, and may affect the latch, jaw motions, tongue placement, lip seal, suck/swallow/breathe pattern and overall feeding behavior. Evidence: PCS. (PMID:2381441)
- 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: PCS. Frequency: 2/2. Onset: Juvenile onset (HP:0003621). (PMID:35513889)
- Retinal pigment epithelial mottling (HP:0007814): Mottling (spots or blotches of different shades) of the retinal pigment epithelium, i.e., localized or generalized fundus pigment granularity associated with processes at the level of the retinal pigment epithelium. Evidence: PCS. (PMID:16603246)
- Metaphyseal widening (HP:0003016): Abnormal widening of the metaphyseal regions of long bones. Evidence: IEA. (OMIM:219800)
- Hypopigmentation of hair (HP:0005599). Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- Reduced blood urea nitrogen (HP:0031969): An abnormally low concentration of urea nitrogen in the blood. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- Medullary nephrocalcinosis (HP:0012408): The deposition of calcium salts in the parenchyma of the renal medulla (innermost part of the kidney). Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- Male infertility (HP:0003251). Evidence: IEA. (OMIM:219800)
- Pigmentary retinopathy (HP:0000580): An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. Evidence: TAS. (OMIM:219800)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: IEA. (OMIM:219800)
- Diabetes mellitus (HP:0000819): A group of abnormalities characterized by hyperglycemia and glucose intolerance. Evidence: PCS. Frequency: 6/13. Onset: Adult onset (HP:0003581). (PMID:35997069)
- Hypomagnesemia (HP:0002917): The concentration of magnesium in the blood circulation is below the lower limit of normal. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 19/23. (PMID:20803298)
- Blindness (HP:0000618): Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation. Evidence: PCS. Frequency: 1/1. Onset: Young adult onset (HP:0011462). (PMID:11116719)
- Blindness (HP:0000618): Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation. Evidence: PCS. Frequency: 0/23. (PMID:20803298)
- Photophobia (HP:0000613): Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light. Evidence: PCS. Onset: Juvenile onset (HP:0003621). (PMID:12110740)
- Dehydration (HP:0001944). Evidence: PCS. Frequency: 2/2. Onset: Infantile onset (HP:0003593). (PMID:35513889)
- Reduced visual acuity (HP:0007663). Evidence: PCS. (PMID:12110740)
- Weight loss (HP:0001824): Reduction of total body weight. Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- Corneal crystals (HP:0000531). Evidence: PCS. Frequency: 187/187. (PMID:11001803;PMID:35513889;PMID:24464559)
- Cerebral calcification (HP:0002514): The presence of calcium deposition within the cerebrum. Evidence: PCS. Frequency: 9/33. Onset: Adult onset (HP:0003581). (PMID:21900880)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:219800)
- Rachitic rosary (HP:0000897): A row of beadlike prominences at the junction of a rib and its cartilage (i.e., enlarged costochondral joints), resembling a rosary. Note that rachitic rosary would have one bead per rib (a swelling at the costochondral junction), while beaded ribs in the context of multiple rib fractures have multiple beads (fractures) along the same rib. Evidence: IEA. (OMIM:219800)
- 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: 11/18. (PMID:35513889;PMID:24464559;PMID:31672123)
- Dysphagia (HP:0002015): Difficulty in swallowing. Evidence: PCS. Onset: Adult onset (HP:0003581). (PMID:30685240)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: IEA. (OMIM:219800)
- Bone marrow cystine accumulation (HP:6001033): The presence of cystine crystals in bone marrow cells as demonstrated in a fresh bone marrow aspiration sample. Evidence: PCS. Frequency: 10/10. (PMID:28871612)
- Hepatic cystine accumulation (HP:6001032): Accumulation of cystine in the liver. Evidence: PCS. (PMID:32727395)
- Cystine nephrolithiasis (HP:6001031): A cystine stone is a type of kidney stone that is yellowish brown with a granular surface. They are observed in individuals with Cystinuria and tend to be of early onset, to occur repeatedly, and to be associated with urinary tract infections. Evidence: PCS. (PMID:32727395)
- 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: PCS. Frequency: 2/2. (PMID:35513889)
- Polydipsia (HP:0001959): Excessive thirst manifested by excessive fluid intake. Evidence: PCS. Frequency: 1/1. (PMID:31672123)
- Polydipsia (HP:0001959): Excessive thirst manifested by excessive fluid intake. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
- Polydipsia (HP:0001959): Excessive thirst manifested by excessive fluid intake. Evidence: PCS. Frequency: 8/13. Onset: Infantile onset (HP:0003593). (PMID:35997069)
- Visual impairment (HP:0000505): Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery. Evidence: PCS. (PMID:12110740)
- Delayed puberty (HP:0000823): Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty. Evidence: IEA. (OMIM:219800)
- Polyuria (HP:0000103): An increased rate of urine production. Evidence: PCS. Frequency: 9/14. (PMID:35997069;PMID:31672123)
- Male hypogonadism (HP:0000026): Decreased functionality of the male gonad, i.e., of the testis, with reduced spermatogenesis or testosterone synthesis. Evidence: PCS. Onset: Adult onset (HP:0003581). (PMID:12110740)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: IEA. (OMIM:219800)
- 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: PCS. Frequency: 1/1. (PMID:31672123)
- 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: PCS. Frequency: 14/15. Onset: Infantile onset (HP:0003593). (PMID:24464559)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 10/13. (PMID:35997069)
- Kidney stone (HP:0000787): Kidney stones (calculi) are mineral concretions in the renal calyces and pelvis that are found free or attached to the renal papillae. Evidence: PCS. Frequency: 2/2. (PMID:35513889)
These phenotypes are associated with the disease nephropathic cystinosis (OMIM:219800).