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Xanthinuria type II(XAN2)

MedGen UID:
350953
Concept ID:
C1863688
Disease or Syndrome
Synonyms: Xanthine dehydrogenase and aldehyde oxidase combined deficiency of; Xanthinuria type 2; XDH and AOX dual deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
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).
 
Gene (location): MOCOS (18q12.2)
 
Monarch Initiative: MONDO:0011346
OMIM®: 603592
Orphanet: ORPHA93602

Definition

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). [from OMIM]

Additional description

From MedlinePlus Genetics
Researchers have described two major forms of hereditary xanthinuria, types I and II. The types are distinguished by the enzymes involved; they have the same signs and symptoms.

Hereditary xanthinuria is a condition that most often affects the kidneys. It is characterized by high levels of a compound called xanthine and very low levels of another compound called uric acid in the blood and urine. The excess xanthine can accumulate in the kidneys and other tissues. In the kidneys, xanthine forms tiny crystals that occasionally build up to create kidney stones. These stones can impair kidney function and ultimately cause kidney failure. Related signs and symptoms can include abdominal pain, recurrent urinary tract infections, and blood in the urine (hematuria). Less commonly, xanthine crystals build up in the muscles, causing pain and cramping. In some people with hereditary xanthinuria, the condition does not cause any health problems.  https://medlineplus.gov/genetics/condition/hereditary-xanthinuria

Clinical features

From HPO
Myalgia
MedGen UID:
68541
Concept ID:
C0231528
Sign or Symptom
Pain in muscle.
Xanthinuria
MedGen UID:
450997
Concept ID:
C0220988
Disease or Syndrome
An increased concentration of xanthine in the urine.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
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.
Increased urinary hypoxanthine level
MedGen UID:
1841541
Concept ID:
C5826349
Finding
The concentration of hypoxanthine in the urine, normalized for urine concentration, is above the upper limit of normal.
Hypouricemia
MedGen UID:
113163
Concept ID:
C0221333
Finding
An abnormally low level of uric acid in the blood.
Hyperxanthinemia
MedGen UID:
1684761
Concept ID:
C5139051
Finding
An increased level of xanthine in the blood circulation.
Increased circulating hypoxanthine concentration
MedGen UID:
1815082
Concept ID:
C5706176
Finding
Elevated concentration of hypoxanthine in the blood circulation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Xanthinuria type II in Orphanet.

Recent clinical studies

Etiology

Sebesta I, Stiburkova B, Krijt J
Nucleosides Nucleotides Nucleic Acids 2018;37(6):324-328. Epub 2018 May 3 doi: 10.1080/15257770.2018.1460478. PMID: 29723117

Diagnosis

Stiburkova B, Pavelcova K, Petru L, Krijt J
Toxicol Appl Pharmacol 2018 Aug 15;353:102-108. Epub 2018 Jun 20 doi: 10.1016/j.taap.2018.06.015. PMID: 29935280
Sebesta I, Stiburkova B, Krijt J
Nucleosides Nucleotides Nucleic Acids 2018;37(6):324-328. Epub 2018 May 3 doi: 10.1080/15257770.2018.1460478. PMID: 29723117
Ichida K, Amaya Y, Okamoto K, Nishino T
Int J Mol Sci 2012 Nov 21;13(11):15475-95. doi: 10.3390/ijms131115475. PMID: 23203137Free PMC Article
Peretz H, Naamati MS, Levartovsky D, Lagziel A, Shani E, Horn I, Shalev H, Landau D
Mol Genet Metab 2007 May;91(1):23-9. Epub 2007 Mar 23 doi: 10.1016/j.ymgme.2007.02.005. PMID: 17368066
Zannolli R, Micheli V, Mazzei MA, Sacco P, Piomboni P, Bruni E, Miracco C, de Santi MM, Terrosi Vagnoli P, Volterrani L, Pellegrini L, Livi W, Lucani B, Gonnelli S, Burlina AB, Jacomelli G, Macucci F, Pucci L, Fimiani M, Swift JA, Zappella M, Morgese G
J Med Genet 2003 Nov;40(11):e121. doi: 10.1136/jmg.40.11.e121. PMID: 14627688Free PMC Article

Therapy

Stiburkova B, Pavelcova K, Petru L, Krijt J
Toxicol Appl Pharmacol 2018 Aug 15;353:102-108. Epub 2018 Jun 20 doi: 10.1016/j.taap.2018.06.015. PMID: 29935280

Prognosis

Peretz H, Naamati MS, Levartovsky D, Lagziel A, Shani E, Horn I, Shalev H, Landau D
Mol Genet Metab 2007 May;91(1):23-9. Epub 2007 Mar 23 doi: 10.1016/j.ymgme.2007.02.005. PMID: 17368066

Clinical prediction guides

Grases F, Costa-Bauza A, Roig J, Rodriguez A
PLoS One 2018;13(8):e0198881. Epub 2018 Aug 29 doi: 10.1371/journal.pone.0198881. PMID: 30157195Free PMC Article
Stiburkova B, Pavelcova K, Petru L, Krijt J
Toxicol Appl Pharmacol 2018 Aug 15;353:102-108. Epub 2018 Jun 20 doi: 10.1016/j.taap.2018.06.015. PMID: 29935280
Peretz H, Naamati MS, Levartovsky D, Lagziel A, Shani E, Horn I, Shalev H, Landau D
Mol Genet Metab 2007 May;91(1):23-9. Epub 2007 Mar 23 doi: 10.1016/j.ymgme.2007.02.005. PMID: 17368066