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Nephrolithiasis

MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
Synonyms: Kidney stone; Kidney stones
SNOMED CT: Kidney stone (95570007); Renal stone (95570007); Nephrolith (95570007); Renal calculus (95570007); Calculus of kidney (95570007); Nephrolithiasis (95570007); Kidney calculus (95570007)
 
HPO: HP:0000787
Monarch Initiative: MONDO:0008171

Definition

The presence of calculi (stones) in the kidneys. [from HPO]

Conditions with this feature

Alkaptonuria
MedGen UID:
1413
Concept ID:
C0002066
Disease or Syndrome
Alkaptonuria is caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The three major features of alkaptonuria are dark urine or urine that turns dark on standing, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and larger joints. Ochronosis generally occurs after age 30 years; arthritis often begins in the third decade. Other manifestations can include pigment in the sclera, ear cartilage, and skin of the hands; aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation; renal stones; prostate stones; and hypothyroidism.
Beckwith-Wiedemann syndrome
MedGen UID:
2562
Concept ID:
C0004903
Disease or Syndrome
Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.
Cystinuria
MedGen UID:
8226
Concept ID:
C0010691
Disease or Syndrome
Cystinuria is an autosomal disorder characterized by impaired epithelial cell transport of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the proximal renal tubule and gastrointestinal tract. The impaired renal reabsorption of cystine and its low solubility causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis, and, rarely, renal failure (summary by Barbosa et al., 2012).
Wilson disease
MedGen UID:
42426
Concept ID:
C0019202
Disease or Syndrome
Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to older than 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.
Lesch-Nyhan syndrome
MedGen UID:
9721
Concept ID:
C0023374
Disease or Syndrome
HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of HPRT1 disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; HPRT1-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and HPRT1-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. It is now recognized that these neurobehavioral phenotypes cluster along a continuum from severe to mild.
Pituitary dependent hypercortisolism
MedGen UID:
66381
Concept ID:
C0221406
Disease or Syndrome
AIP familial isolated pituitary adenoma (AIP-FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and nonfunctioning pituitary adenomas (NFPA). Rarely TSH-secreting adenomas (thyrotropinomas) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-FIPA is usually in the second or third decade.
Partial hypoxanthine-guanine phosphoribosyltransferase deficiency
MedGen UID:
82770
Concept ID:
C0268117
Disease or Syndrome
HPRT1 disorders, caused by deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt), are typically associated with clinical evidence for overproduction of uric acid (hyperuricemia, nephrolithiasis, and/or gouty arthritis) and varying degrees of neurologic and/or behavioral problems. Historically, three phenotypes were identified in the spectrum of HPRT1 disorders: Lesch-Nyhan disease (LND) at the most severe end with motor dysfunction resembling severe cerebral palsy, intellectual disability, and self-injurious behavior; HPRT1-related neurologic dysfunction (HND) in the intermediate range with similar but fewer severe neurologic findings than LND and no self-injurious behavior; and HPRT1-related hyperuricemia (HRH) at the mild end without overt neurologic deficits. It is now recognized that these neurobehavioral phenotypes cluster along a continuum from severe to mild.
Adenine phosphoribosyltransferase deficiency
MedGen UID:
82772
Concept ID:
C0268120
Disease or Syndrome
Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production and renal excretion of 2,8-dihydroxyadenine (DHA), which leads to kidney stone formation and crystal-induced kidney damage (i.e., DHA crystal nephropathy) causing acute kidney injury episodes and progressive chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected persons symptoms do not occur until adulthood. If adequate treatment is not provided, approximately 20%-25% of affected individuals develop end-stage renal disease (ESRD), usually in adult life.
Glucose-6-phosphate transport defect
MedGen UID:
78644
Concept ID:
C0268146
Disease or Syndrome
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys resulting in hepatomegaly and nephromegaly. Severely affected infants present in the neonatal period with severe hypoglycemia due to fasting intolerance. More commonly, untreated infants present at age three to four months with hepatomegaly, severe hypoglycemia with or without seizures, lactic acidosis, hyperuricemia, and hypertriglyceridemia. Affected children typically have doll-like faces with full cheeks, relatively thin extremities, short stature, and a protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function and development of reduced or dysfunctional von Willebrand factor can lead to a bleeding tendency with frequent epistaxis and menorrhagia in females. Individuals with untreated GSDIb are more likely to develop impaired neutrophil and monocyte function as well as chronic neutropenia resulting in recurrent bacterial infections, gingivitis, periodontitis, and genital and intestinal ulcers. Long-term complications of untreated GSDI include short stature, osteoporosis, delayed puberty, renal disease (including proximal and distal renal tubular acidosis, renal stones, and renal failure), gout, systemic hypertension, pulmonary hypertension, hepatic adenomas with potential for malignancy, pancreatitis, and polycystic ovaries. Seizures and cognitive impairment may occur in individuals with prolonged periods of hypoglycemia. Normal growth and puberty are expected in treated children. Most affected individuals live into adulthood.
Primary hypomagnesemia
MedGen UID:
120640
Concept ID:
C0268448
Disease or Syndrome
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a progressive renal disorder characterized by excessive urinary Ca(2+) and Mg(2+) excretion. There is progressive loss of kidney function, and in about 50% of cases, the need for renal replacement therapy arises as early as the second decade of life (summary by Muller et al., 2006). Amelogenesis imperfecta may also be present in some patients (Bardet et al., 2016). A similar disorder with renal magnesium wasting, renal failure, and nephrocalcinosis (HOMG5; 248190) is caused by mutations in another tight-junction gene, CLDN19 (610036), and is distinguished by the association of severe ocular involvement. For a discussion of phenotypic and genetic heterogeneity of familial hypomagnesemia, see HOMG1 (602014).
Autosomal dominant hypocalcemia 1
MedGen UID:
87438
Concept ID:
C0342345
Disease or Syndrome
Autosomal dominant hypocalcemia-1 is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% of patients have mild or asymptomatic hypocalcemia; about 50% have paresthesias, carpopedal spasm, and seizures; about 10% have hypercalciuria with nephrocalcinosis or kidney stones; and more than 35% have ectopic and basal ganglia calcifications (summary by Nesbit et al., 2013). Thakker (2001) noted that patients with gain-of-function mutations in the CASR gene, resulting in generally asymptomatic hypocalcemia with hypercalciuria, have low-normal serum PTH concentrations and have often been diagnosed with hypoparathyroidism because of the insensitivity of earlier PTH assays. Because treatment with vitamin D to correct the hypocalcemia in these patients causes hypercalciuria, nephrocalcinosis, and renal impairment, these patients need to be distinguished from those with other forms of hypoparathyroidism (see 146200). Thakker (2001) suggested the designation 'autosomal dominant hypocalcemic hypercalciuria' for this CASR-related disorder. Genetic Heterogeneity of Autosomal Dominant Hypocalcemia Autosomal dominant hypocalcemia-2 (HYPOC2; 615361) is caused by mutation in the GNA11 gene (139313) on chromosome 19p13.
Familial hypocalciuric hypercalcemia 1
MedGen UID:
137973
Concept ID:
C0342637
Disease or Syndrome
Familial hypocalciuric hypercalcemia (HHC) is a heritable disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. HHC is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone (PTH; 168450) level. Hypermagnesemia is typically present. Individuals with HHC are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults (summary by Hannan et al., 2010). Characteristic features of familial hypocalciuric hypercalcemia include mild to moderate hypercalcemia, nonsuppressed parathyroid hormone, relative hypocalciuria while hypercalcemic (calcium/creatinine clearance ratio less than 0.01, or 24-hr urine calcium less than 6.25 mmol), almost 100% penetrance of hypercalcemia from birth, absence of complications, persistence of hypercalcemia following subtotal parathyroidectomy, and normal parathyroid size, weight, and histology at surgery. However, atypical presentations with severe hypercalcemia, hypercalciuria with or without nephrolithiasis or nephrocalcinosis, kindreds with affected members displaying either hypercalciuria or hypocalciuria, postoperative normocalcemia, and pancreatitis have all been described in FHH (Warner et al., 2004). Genetic Heterogeneity of Hypocalciuric Hypercalcemia Familial hypocalciuric hypercalcemia type II (HHC2; 145981) is caused by mutation in the GNA11 gene (139313) on chromosome 19p13, and HHC3 (600740) is caused by mutation in the AP2S1 gene (602242) on chromosome 19q13.
Renal tubular acidosis with progressive nerve deafness
MedGen UID:
98336
Concept ID:
C0403554
Disease or Syndrome
Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations can also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration. Electrolyte manifestations include hyperchloremic non-anion gap metabolic acidosis and hypokalemia. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function. Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in ATP6V0A4-, ATP6V1B1-, and FOXI1-dRTA), and hereditary hemolytic anemia (in some individuals with SLC4A1-dRTA).
X-linked recessive nephrolithiasis with renal failure
MedGen UID:
96047
Concept ID:
C0403720
Disease or Syndrome
X-linked recessive nephrolithiasis with renal failure (XRN) is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrolithiasis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
Renal cysts and diabetes syndrome
MedGen UID:
96569
Concept ID:
C0431693
Disease or Syndrome
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural and functional kidney anomalies occur in 85% to 90% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Sucrase-isomaltase deficiency
MedGen UID:
220924
Concept ID:
C1283620
Disease or Syndrome
Congenital sucrose-isomaltase deficiency (CSID) is an autosomal recessive disorder characterized by absence of sucrase and most of the maltase digestive activity within the sucrase-isomaltase enzyme complex, with the isomaltase activity varying from absent to normal. The large amounts of unabsorbed disaccharides create osmotic-fermatative diarrhea with symptoms such as vomiting, flatulence, and abdominal pain (summary by Sander et al., 2006).
Hyperparathyroidism 2 with jaw tumors
MedGen UID:
310065
Concept ID:
C1704981
Neoplastic Process
The spectrum of CDC73-related disorders includes the following phenotypes: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Primary hyperparathyroidism, the main finding of HPT-JT syndrome, occurs in up to 95% of affected individuals; onset is typically in late adolescence or early adulthood. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. In approximately 10%-15% of individuals, primary hyperparathyroidism is caused by parathyroid carcinoma. Ossifying fibromas of the mandible or maxilla, also known as cementifying fibromas and cemento-ossifying fibromas, occur in 30%-40% of individuals with HPT-JT syndrome. Although benign, these tumors can be locally aggressive and may continue to enlarge if not treated. Approximately 20% of individuals with HPT-JT syndrome have kidney lesions, most commonly cysts; renal hamartomas and (more rarely) Wilms tumor have also been reported. Benign and malignant uterine tumors appear to be common in women with HPT-JT syndrome. Parathyroid carcinoma. Most parathyroid carcinomas are functional, resulting in hyperparathyroidism and a high serum calcium level; however, nonfunctioning parathyroid carcinomas are also rarely described in individuals with a CDC73-related disorder. A germline CDC73 pathogenic variant has been identified in 20%-29% of individuals with apparently sporadic parathyroid carcinoma. Familial isolated hyperparathyroidism (FIHP). FIHP is characterized by primary hyperparathyroidism without other associated syndromic features. Individuals with CDC73-related FIHP tend to have a more severe clinical presentation and younger age of onset than individuals with FIHP in whom a CDC73 pathogenic variant has not been identified.
Congenital generalized lipodystrophy type 1
MedGen UID:
318592
Concept ID:
C1720862
Disease or Syndrome
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Congenital generalized lipodystrophy type 2
MedGen UID:
318593
Concept ID:
C1720863
Congenital Abnormality
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Familial hypocalciuric hypercalcemia 3
MedGen UID:
322173
Concept ID:
C1833372
Disease or Syndrome
Any familial hypocalciuric hypercalcemia in which the cause of the disease is a mutation in the AP2S1 gene.
Familial hypocalciuric hypercalcemia 2
MedGen UID:
374447
Concept ID:
C1840347
Disease or Syndrome
Familial hypocalciuric hypercalcemia type II (HHC2) is an autosomal dominant disorder characterized by lifelong elevations of serum calcium concentrations with low urinary calcium excretion and normal circulating parathyroid hormone concentrations in most patients. Patients are generally asymptomatic (summary by Nesbit et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of hypocalciuric hypercalcemia, see HHC1 (145980).
Hypophosphatemic rickets, X-linked recessive
MedGen UID:
335115
Concept ID:
C1845168
Disease or Syndrome
X-linked recessive hypophosphatemic rickets is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
Hypotonia-cystinuria syndrome
MedGen UID:
341133
Concept ID:
C1848030
Disease or Syndrome
A rare, genetic disorder of amino acid absorption and transport, characterized by generalized hypotonia at birth, neonatal/infantile failure to thrive (followed by hyperphagia and rapid weight gain in late childhood), cystinuria type 1, nephrolithiasis, growth retardation due to growth hormone deficiency, and minor facial dysmorphism. Dysmorphic features mainly include dolichocephaly and ptosis. Nephrolithiasis occurs at variable ages.
Dent disease type 1
MedGen UID:
336322
Concept ID:
C1848336
Disease or Syndrome
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD.
Renal tubular acidosis 3
MedGen UID:
336601
Concept ID:
C1849435
Disease or Syndrome
Renal coloboma syndrome
MedGen UID:
339002
Concept ID:
C1852759
Disease or Syndrome
PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal coloboma syndrome and characterized by renal hypodysplasia and abnormalities of the optic nerve; with improved access to molecular testing, a wider range of phenotypes has been recognized in association with pathogenic variants in PAX2. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77% of affected individuals. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency / renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Uric acid nephrolithiasis has been reported. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with PAX2–related disorder. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity. PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis.
Dicarboxylic aminoaciduria
MedGen UID:
387782
Concept ID:
C1857253
Disease or Syndrome
Dicarboxylic aminoaciduria (DCBXA) is characterized by a striking excretion of urinary glutamate and aspartate, resulting from the incomplete reabsorption of anionic amino acids from the glomerular filtrate in the kidney. Patients may have impaired intellectual development (summary by Bailey et al., 2011).
Xanthinuria type II
MedGen UID:
350953
Concept ID:
C1863688
Disease or Syndrome
Xanthinuria type II (XAN2) is an autosomal recessive inborn error of metabolism resulting from a defect in the synthesis of the molybdenum cofactor, which is necessary for the 2 enzymes that degrade xanthine: XDH (607633) and AOX1 (602841). Most individuals with type II xanthinuria are asymptomatic, but some develop urinary tract calculi, acute renal failure, or myositis due to tissue deposition of xanthine. Laboratory studies show increased serum and urinary hypoxanthine and xanthine and decreased serum and urinary uric acid (summary by Ichida et al., 2001). Two clinically similar but distinct forms of xanthinuria are recognized. In type I xanthinuria (XAN1; 278300), there is an isolated deficiency of xanthine dehydrogenase resulting from mutation in the XDH gene; in type II, there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase. Type I patients can metabolize allopurinol, whereas type II patients cannot (Simmonds et al., 1995).
Plasminogen deficiency, type I
MedGen UID:
369859
Concept ID:
C1968804
Disease or Syndrome
Congenital plasminogen deficiency is a rare autosomal recessive disorder characterized clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. A slightly increased female:male ratio has been observed (1.4:1 to 2:1) (Schuster and Seregard, 2003; Tefs et al., 2006). Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms, whereas type II plasminogen deficiency, also known as 'dysplasminogenemia,' is characterized by decreased plasminogen activity with normal or slightly reduced antigen levels. Patients with type II deficiency are usually asymptomatic. Ligneous conjunctivitis and pseudomembranous formation has only been associated with type I plasminogen deficiency. Presumably, normal amounts of plasminogen antigen with decreased activity, as seen in type II, is sufficient for normal wound healing (Schuster and Seregard, 2003).
Hypophosphatemic nephrolithiasis/osteoporosis 2
MedGen UID:
394127
Concept ID:
C2676782
Disease or Syndrome
Hypophosphatemic nephrolithiasis/osteoporosis 1
MedGen UID:
436776
Concept ID:
C2676786
Disease or Syndrome
Hypouricemia, renal, 2
MedGen UID:
436974
Concept ID:
C2677549
Disease or Syndrome
Renal hypouricemia is a common inherited disorder characterized by impaired renal urate reabsorption and subsequent low serum urate levels. It may be associated with severe complications such as exercise-induced acute renal failure (EIARF) and nephrolithiasis (summary by Matsuo et al., 2008). For additional phenotypic information and a discussion of genetic heterogeneity of renal hypouricemia, see RHUC1 (220150).
Glycogen storage disease due to glucose-6-phosphatase deficiency type IA
MedGen UID:
415885
Concept ID:
C2919796
Disease or Syndrome
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys resulting in hepatomegaly and nephromegaly. Severely affected infants present in the neonatal period with severe hypoglycemia due to fasting intolerance. More commonly, untreated infants present at age three to four months with hepatomegaly, severe hypoglycemia with or without seizures, lactic acidosis, hyperuricemia, and hypertriglyceridemia. Affected children typically have doll-like faces with full cheeks, relatively thin extremities, short stature, and a protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function and development of reduced or dysfunctional von Willebrand factor can lead to a bleeding tendency with frequent epistaxis and menorrhagia in females. Individuals with untreated GSDIb are more likely to develop impaired neutrophil and monocyte function as well as chronic neutropenia resulting in recurrent bacterial infections, gingivitis, periodontitis, and genital and intestinal ulcers. Long-term complications of untreated GSDI include short stature, osteoporosis, delayed puberty, renal disease (including proximal and distal renal tubular acidosis, renal stones, and renal failure), gout, systemic hypertension, pulmonary hypertension, hepatic adenomas with potential for malignancy, pancreatitis, and polycystic ovaries. Seizures and cognitive impairment may occur in individuals with prolonged periods of hypoglycemia. Normal growth and puberty are expected in treated children. Most affected individuals live into adulthood.
Nephropathic cystinosis
MedGen UID:
419735
Concept ID:
C2931187
Disease or Syndrome
Cystinosis comprises three allelic phenotypes: Nephropathic cystinosis in untreated children is characterized by renal Fanconi syndrome, poor growth, hypophosphatemic/calcipenic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine in almost all cells, leading to cellular dysfunction with tissue and organ impairment. The typical untreated child has short stature, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these interventions, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized clinically only by photophobia resulting from corneal cystine crystal accumulation.
Osteogenesis imperfecta type 10
MedGen UID:
462561
Concept ID:
C3151211
Disease or Syndrome
Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type X is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclera (Christiansen et al., 2010).
Familial steroid-resistant nephrotic syndrome with sensorineural deafness
MedGen UID:
766263
Concept ID:
C3553349
Disease or Syndrome
Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen.
Aldosterone-producing adenoma with seizures and neurological abnormalities
MedGen UID:
815939
Concept ID:
C3809609
Disease or Syndrome
A rare, genetic, neurologic disease characterized by primary hyperaldosteronism presenting with early-onset, severe hypertension, hypokalemia and neurological manifestations (including seizures, severe hypotonia, spasticity, cerebral palsy and profound developmental delay/intellectual disability).
Hypercalcemia, infantile, 1
MedGen UID:
934200
Concept ID:
C4310232
Disease or Syndrome
Infantile hypercalcemia is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. An epidemic of idiopathic infantile hypercalcemia occurred in the United Kingdom in the 1950s after the implementation of an increased prophylactic dose of vitamin D supplementation; however, the fact that most infants receiving the prophylaxis remained unaffected suggested that an intrinsic hypersensitivity to vitamin D might be implicated in the pathogenesis (summary by Schlingmann et al., 2011). Genetic Heterogeneity Infantile hypercalcemia-2 (HCINF2; 616963) is caused by mutation in the SLC34A1 gene (182309) on chromosome 5q35.
Yao syndrome
MedGen UID:
934587
Concept ID:
C4310620
Disease or Syndrome
Yao syndrome (YAOS) is an autoinflammatory disease characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. The disorder is associated with specific NOD2 variants (and Shen, 2017).
Chromosome 19q13.11 deletion syndrome, proximal
MedGen UID:
935013
Concept ID:
C4311046
Disease or Syndrome
Proximal chromosome 19q13.11 deletion syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed development, intellectual disability with poor speech, feeding difficulties, and autistic features. Some patients may have additional features, including renal tract anomalies (summary by Caubit et al., 2016).
Hyperparathyroidism 4
MedGen UID:
1386327
Concept ID:
C4479229
Disease or Syndrome
Any familial isolated hyperparathyroidism in which the cause of the disease is a mutation in the GCM2 gene.
HELIX syndrome
MedGen UID:
1621482
Concept ID:
C4522164
Disease or Syndrome
HELIX syndrome is an autosomal recessive disorder characterized by Hypohidrosis, Electrolyte imbalance, Lacrimal gland dysfunction, Ichthyosis, and Xerostomia (summary by Hadj-Rabia et al., 2018).
Zimmermann-Laband syndrome 1
MedGen UID:
1639277
Concept ID:
C4551773
Disease or Syndrome
Zimmermann-Laband syndrome is a rare disorder characterized by gingival fibromatosis, dysplastic or absent nails, hypoplasia of the distal phalanges, scoliosis, hepatosplenomegaly, hirsutism, and abnormalities of the cartilage of the nose and/or ears (summary by Balasubramanian and Parker, 2010). Genetic Heterogeneity of Zimmermann-Laband Syndrome ZLS2 (616455) is caused by mutation in the ATP6V1B2 gene (606939) on chromosome 8p21. ZLS3 (618658) is caused by mutation in the KCNN3 gene (602983) on chromosome 1q21.
Renal hypomagnesemia 5 with ocular involvement
MedGen UID:
1648449
Concept ID:
C4721891
Disease or Syndrome
HOMG5 is an autosomal recessive disorder characterized by severe renal magnesium wasting, progressive renal failure, nephrocalcinosis, and severe visual impairment (Konrad et al., 2006). Amelogenesis imperfecta may also be present in some patients (Yamaguti et al., 2017). For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014.
Autosomal recessive Robinow syndrome
MedGen UID:
1770070
Concept ID:
C5399974
Disease or Syndrome
ROR2-related Robinow syndrome is characterized by distinctive craniofacial features, skeletal abnormalities, and other anomalies. Craniofacial features include macrocephaly, broad prominent forehead, low-set ears, ocular hypertelorism, prominent eyes, midface hypoplasia, short upturned nose with depressed nasal bridge and flared nostrils, large and triangular mouth with exposed incisors and upper gums, gum hypertrophy, misaligned teeth, ankyloglossia, and micrognathia. Skeletal abnormalities include short stature, mesomelic or acromesomelic limb shortening, hemivertebrae with fusion of thoracic vertebrae, and brachydactyly. Other common features include micropenis with or without cryptorchidism in males and reduced clitoral size and hypoplasia of the labia majora in females, renal tract abnormalities, and nail hypoplasia or dystrophy. The disorder is recognizable at birth or in early childhood.
Azoospermia, obstructive, with nephrolithiasis
MedGen UID:
1779119
Concept ID:
C5542351
Disease or Syndrome
Obstructive azoospermia with nephrolithiasis (OAZON) is characterized by male infertility due to obstruction at the head of the epididymis, as well as hypercalciuria and kidney stones (Askari et al., 2019).
Megacystis-microcolon-intestinal hypoperistalsis syndrome 4
MedGen UID:
1783600
Concept ID:
C5543519
Disease or Syndrome
Megacystis-microcolon-intestinal hypoperistalsis syndrome-4 (MMIHS4) is a severe early-onset disorder characterized by impaired smooth muscle contractility in the bladder and intestines (Kandler et al., 2020). For a discussion of genetic heterogeneity of MMIHS, see 249210.
Mucopolysaccharidosis, type 10
MedGen UID:
1794274
Concept ID:
C5562064
Disease or Syndrome
Mucopolysaccharidosis type X (MPS10) is an autosomal recessive childhood-onset disorder associated with disproportionate short-trunk short stature and skeletal, cardiac, and ophthalmologic abnormalities (Verheyen et al., 2022).
Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly
MedGen UID:
1808159
Concept ID:
C5676961
Disease or Syndrome
Autosomal recessive intellectual developmental disorder-75 with neuropsychiatric features and variant lissencephaly (MRT75) is characterized by global developmental delay apparent from infancy or early childhood and moderate to profoundly impaired intellectual development. Most affected individuals have behavioral abnormalities, including aggression and ADHD; a few have psychiatric manifestations, including psychosis. More variable additional features include well-controlled seizures and dysmorphic facial features. Brain imaging often shows frontal predominant pachygyria or other gyri/sulci abnormalities, consistent with a variant of lissencephaly and a malformation of cortical development (MCD) (summary by Zaki et al., 2021).
Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures
MedGen UID:
1823981
Concept ID:
C5774208
Disease or Syndrome
Neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures (NEDMIMS) is an autosomal recessive disorder characterized by severe global developmental delay apparent from infancy, impaired intellectual development, progressive microcephaly, and early-onset seizures that may be refractory to treatment. Affected individuals have poor overall growth and may have various movement abnormalities, including hypo- and hypertonia. Behavioral problems may also be observed (Klockner et al., 2022).
Hypersulfaturia
MedGen UID:
1841147
Concept ID:
C5830511
Disease or Syndrome
Hypersulfaturia (HYSULF) is an autosomal recessive condition characterized by increased urinary sulfate excretion due to defective renal sulfate reabsorption. The single reported patient with this condition presented with adult-onset perichondritis of the costovertebral joints (Pfau et al., 2023).
Nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosis
MedGen UID:
1841152
Concept ID:
C5830516
Disease or Syndrome
Calcium oxalate nephrolithiasis-2 with or without nephrocalcinosis (CAON2) is an autosomal dominant disorder of renal function characterized by the recurrent formation of CaOx kidney stones. The age at onset is highly variable, ranging from childhood to adult. Most affected individuals have concurrent nephrocalcinosis. Renal function is generally preserved (Majmundar et al., 2023). See also CAON1 (167030).
Autosomal dominant distal renal tubular acidosis
MedGen UID:
963849
Concept ID:
CN280572
Disease or Syndrome
Individuals with hereditary distal renal tubular acidosis (dRTA) typically present in infancy with failure to thrive, although later presentations can occur, especially in individuals with autosomal dominant SLC4A1-dRTA. Initial clinical manifestations can also include emesis, polyuria, polydipsia, constipation, diarrhea, decreased appetite, and episodes of dehydration. Electrolyte manifestations include hyperchloremic non-anion gap metabolic acidosis and hypokalemia. Renal complications of dRTA include nephrocalcinosis, nephrolithiasis, medullary cysts, and impaired renal function. Additional manifestations include bone demineralization (rickets, osteomalacia), growth deficiency, sensorineural hearing loss (in ATP6V0A4-, ATP6V1B1-, and FOXI1-dRTA), and hereditary hemolytic anemia (in some individuals with SLC4A1-dRTA).

Professional guidelines

PubMed

Daudon M, Frochot V, Bazin D, Jungers P
Drugs 2018 Feb;78(2):163-201. doi: 10.1007/s40265-017-0853-7. PMID: 29264783
Sakhaee K, Maalouf NM, Sinnott B
J Clin Endocrinol Metab 2012 Jun;97(6):1847-60. Epub 2012 Mar 30 doi: 10.1210/jc.2011-3492. PMID: 22466339Free PMC Article
Wilkins T, Jarvis K, Patel J
Am Fam Physician 2011 Dec 15;84(12):1365-75. PMID: 22230271

Recent clinical studies

Etiology

Bishop K, Momah T, Ricks J
Prim Care 2020 Dec;47(4):661-671. Epub 2020 Sep 23 doi: 10.1016/j.pop.2020.08.005. PMID: 33121635
Howles SA, Thakker RV
Nat Rev Urol 2020 Jul;17(7):407-421. Epub 2020 Jun 12 doi: 10.1038/s41585-020-0332-x. PMID: 32533118
Mayans L
Prim Care 2019 Jun;46(2):203-212. doi: 10.1016/j.pop.2019.02.001. PMID: 31030821
Ziemba JB, Matlaga BR
Investig Clin Urol 2017 Sep;58(5):299-306. Epub 2017 Aug 10 doi: 10.4111/icu.2017.58.5.299. PMID: 28868500Free PMC Article
Sakhaee K, Maalouf NM, Sinnott B
J Clin Endocrinol Metab 2012 Jun;97(6):1847-60. Epub 2012 Mar 30 doi: 10.1210/jc.2011-3492. PMID: 22466339Free PMC Article

Diagnosis

Cusano NE, Cetani F
Arch Endocrinol Metab 2022 Nov 11;66(5):666-677. doi: 10.20945/2359-3997000000556. PMID: 36382756Free PMC Article
Bishop K, Momah T, Ricks J
Prim Care 2020 Dec;47(4):661-671. Epub 2020 Sep 23 doi: 10.1016/j.pop.2020.08.005. PMID: 33121635
Corbo J, Wang J
Emerg Med Clin North Am 2019 Nov;37(4):637-648. Epub 2019 Aug 19 doi: 10.1016/j.emc.2019.07.004. PMID: 31563199
Mayans L
Prim Care 2019 Jun;46(2):203-212. doi: 10.1016/j.pop.2019.02.001. PMID: 31030821
Manjunath AS, Hofer MD
Med Clin North Am 2018 Mar;102(2):373-385. Epub 2017 Dec 20 doi: 10.1016/j.mcna.2017.10.013. PMID: 29406065

Therapy

Balasubramanian P, Wanner C, Ferreira JP, Ofstad AP, Elsaesser A, Zinman B, Inzucchi SE
J Clin Endocrinol Metab 2022 Jun 16;107(7):e3003-e3007. doi: 10.1210/clinem/dgac154. PMID: 35290464Free PMC Article
Zheng J, Zhang Y, Rasheed H, Walker V, Sugawara Y, Li J, Leng Y, Elsworth B, Wootton RE, Fang S, Yang Q, Burgess S, Haycock PC, Borges MC, Cho Y, Carnegie R, Howell A, Robinson J, Thomas LF, Brumpton BM, Hveem K, Hallan S, Franceschini N, Morris AP, Köttgen A, Pattaro C, Wuttke M, Yamamoto M, Kashihara N, Akiyama M, Kanai M, Matsuda K, Kamatani Y, Okada Y, Walters R, Millwood IY, Chen Z, Davey Smith G, Barbour S, Yu C, Åsvold BO, Zhang H, Gaunt TR
Int J Epidemiol 2022 Jan 6;50(6):1995-2010. Epub 2021 Oct 20 doi: 10.1093/ije/dyab203. PMID: 34999880Free PMC Article
Yang B, Xie Y, Guo M, Rosner MH, Yang H, Ronco C
Clin J Am Soc Nephrol 2018 Oct 8;13(10):1605-1611. Epub 2018 Apr 3 doi: 10.2215/CJN.11571017. PMID: 29615394Free PMC Article
Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y
World J Urol 2017 Sep;35(9):1301-1320. Epub 2017 Feb 17 doi: 10.1007/s00345-017-2008-6. PMID: 28213860
Smith-Bindman R, Aubin C, Bailitz J, Bengiamin RN, Camargo CA Jr, Corbo J, Dean AJ, Goldstein RB, Griffey RT, Jay GD, Kang TL, Kriesel DR, Ma OJ, Mallin M, Manson W, Melnikow J, Miglioretti DL, Miller SK, Mills LD, Miner JR, Moghadassi M, Noble VE, Press GM, Stoller ML, Valencia VE, Wang J, Wang RC, Cummings SR
N Engl J Med 2014 Sep 18;371(12):1100-10. doi: 10.1056/NEJMoa1404446. PMID: 25229916

Prognosis

Singh P, Harris PC, Sas DJ, Lieske JC
Nat Rev Nephrol 2022 Apr;18(4):224-240. Epub 2021 Dec 14 doi: 10.1038/s41581-021-00513-4. PMID: 34907378
Ferraro PM, Bargagli M, Trinchieri A, Gambaro G
Nutrients 2020 Mar 15;12(3) doi: 10.3390/nu12030779. PMID: 32183500Free PMC Article
Ziemba JB, Matlaga BR
Investig Clin Urol 2017 Sep;58(5):299-306. Epub 2017 Aug 10 doi: 10.4111/icu.2017.58.5.299. PMID: 28868500Free PMC Article
Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y
World J Urol 2017 Sep;35(9):1301-1320. Epub 2017 Feb 17 doi: 10.1007/s00345-017-2008-6. PMID: 28213860
Sakhaee K, Maalouf NM, Sinnott B
J Clin Endocrinol Metab 2012 Jun;97(6):1847-60. Epub 2012 Mar 30 doi: 10.1210/jc.2011-3492. PMID: 22466339Free PMC Article

Clinical prediction guides

Balasubramanian P, Wanner C, Ferreira JP, Ofstad AP, Elsaesser A, Zinman B, Inzucchi SE
J Clin Endocrinol Metab 2022 Jun 16;107(7):e3003-e3007. doi: 10.1210/clinem/dgac154. PMID: 35290464Free PMC Article
Yuan S, Larsson SC
Am J Kidney Dis 2022 Jan;79(1):9-14.e1. Epub 2021 Oct 21 doi: 10.1053/j.ajkd.2021.04.018. PMID: 34690004
Schlomer BJ
Curr Opin Pediatr 2020 Apr;32(2):288-294. doi: 10.1097/MOP.0000000000000849. PMID: 31790031
Li X, Meng X, Timofeeva M, Tzoulaki I, Tsilidis KK, Ioannidis JP, Campbell H, Theodoratou E
BMJ 2017 Jun 7;357:j2376. doi: 10.1136/bmj.j2376. PMID: 28592419Free PMC Article
Smith-Bindman R, Aubin C, Bailitz J, Bengiamin RN, Camargo CA Jr, Corbo J, Dean AJ, Goldstein RB, Griffey RT, Jay GD, Kang TL, Kriesel DR, Ma OJ, Mallin M, Manson W, Melnikow J, Miglioretti DL, Miller SK, Mills LD, Miner JR, Moghadassi M, Noble VE, Press GM, Stoller ML, Valencia VE, Wang J, Wang RC, Cummings SR
N Engl J Med 2014 Sep 18;371(12):1100-10. doi: 10.1056/NEJMoa1404446. PMID: 25229916

Recent systematic reviews

D'Ambrosio V, Ferraro PM, Lombardi G, Friso S, Gambaro G
Nutrients 2022 Nov 23;14(23) doi: 10.3390/nu14234961. PMID: 36500991Free PMC Article
Witting C, Langman CB, Assimos D, Baum MA, Kausz A, Milliner D, Tasian G, Worcester E, Allain M, West M, Knauf F, Lieske JC
Clin J Am Soc Nephrol 2021 Mar 8;16(3):487-495. Epub 2020 Sep 8 doi: 10.2215/CJN.08000520. PMID: 32900691Free PMC Article
Carbone A, Al Salhi Y, Tasca A, Palleschi G, Fuschi A, De Nunzio C, Bozzini G, Mazzaferro S, Pastore AL
Minerva Urol Nefrol 2018 Aug;70(4):393-400. Epub 2018 May 31 doi: 10.23736/S0393-2249.18.03113-2. PMID: 29856171
Lucato P, Trevisan C, Stubbs B, Zanforlini BM, Solmi M, Luchini C, Girotti G, Pizzato S, Manzato E, Sergi G, Giannini S, Fusaro M, Veronese N
Osteoporos Int 2016 Nov;27(11):3155-3164. Epub 2016 Jun 11 doi: 10.1007/s00198-016-3658-8. PMID: 27289533
Rendina D, De Filippo G, D'Elia L, Strazzullo P
J Nephrol 2014 Aug;27(4):371-6. Epub 2014 Apr 3 doi: 10.1007/s40620-014-0085-9. PMID: 24696310

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