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Adenine phosphoribosyltransferase deficiency(APRTD)

MedGen UID:
82772
Concept ID:
C0268120
Disease or Syndrome
Synonyms: APRT DEFICIENCY; APRTD; Dihydroxyadeninuria; NEPHROLITHIASIS, DHA; UROLITHIASIS, 2,8-DIHYDROXYADENINE; Urolithiasis, dha
SNOMED CT: Adenine phosphoribosyl transferase deficiency (124274002); Deficiency of AMP pyrophorylase (124274002); Deficiency of adenine phosphoribosyltransferase (124274002)
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): APRT (16q24.3)
 
Monarch Initiative: MONDO:0013869
OMIM®: 614723
Orphanet: ORPHA976

Disease characteristics

Excerpted from the GeneReview: Adenine Phosphoribosyltransferase Deficiency
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. [from GeneReviews]
Authors:
Vidar Orn Edvardsson  |  Amrik Sahota  |  Runolfur Palsson   view full author information

Additional descriptions

From OMIM
APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. The age at onset can range from 5 months to late adulthood; however, as many as 50% of APRT-deficient individuals may be asymptomatic (summary by Sahota et al., 2001). Two types of APRT deficiency have been described based on the level of residual enzyme activity in in vitro studies of erythrocytes. Type I deficiency is characterized by complete enzyme deficiency in intact cells and in cell lysates, whereas type II deficiency is characterized by complete enzyme deficiency in intact cells, but only a partial deficiency in cell lysates. Type II alleles show reduced affinity for phosphoribosyl pyrophosphate (PRPP) compared to wildtype. In both types, APRT activity is not functional in vivo. Type II deficiency is most common among Japanese. Heterozygotes of either type do not appear to have any clinical or biochemical abnormalities (summary by Sahota et al., 2001).  http://www.omim.org/entry/614723
From MedlinePlus Genetics
Adenine phosphoribosyltransferase (APRT) deficiency is an inherited condition that affects the kidneys and urinary tract. The most common feature of this condition is recurrent kidney stones; urinary tract stones are also a frequent symptom. Kidney and urinary tract stones can create blockages in the urinary tract, causing pain during urination and difficulty releasing urine.

Affected individuals can develop features of this condition anytime from infancy to late adulthood. When the condition appears in infancy, the first sign is usually the presence of tiny grains of reddish-brown material in the baby's diaper caused by the passing of stones. Later, recurrent kidney and urinary tract stones can lead to problems with kidney function beginning as early as mid- to late childhood. Approximately half of individuals with APRT deficiency first experience signs and symptoms of the condition in adulthood. The first features in affected adults are usually kidney stones and related urinary problems. Other signs and symptoms of APRT deficiency caused by kidney and urinary tract stones include fever, urinary tract infection, blood in the urine (hematuria), abdominal cramps, nausea, and vomiting.

Without treatment, kidney function can decline, which may lead to end-stage renal disease (ESRD). ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.

The features of this condition and their severity vary greatly among affected individuals, even among members of the same family. It is estimated that 15 to 20 percent of people with APRT deficiency do not have any signs or symptoms of the condition.  https://medlineplus.gov/genetics/condition/adenine-phosphoribosyltransferase-deficiency

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
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).
Oliguria
MedGen UID:
18163
Concept ID:
C0028961
Disease or Syndrome
Low output of urine, clinically classified as an output below 300-500ml/day.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Urolithiasis
MedGen UID:
141536
Concept ID:
C0451641
Disease or Syndrome
Renal stones are formed within the kidneys, and this is called nephrolithiasis. Urolithiasis is a condition that occurs when these stones exit the renal pelvis and move into the remainder of the urinary collecting system, which includes the ureters, bladder, and urethra.
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.
2,8-dihydroxyadenine crystalluria
MedGen UID:
1814409
Concept ID:
C5676845
Finding
The presence of 2,8-dihydroxyadenine crystals in the urine. The crystals appear as round, yellow-brown crystals.
Elevated urinary 2,8-dihydroxyadenine level
MedGen UID:
1864093
Concept ID:
C5937529
Finding
The amount of 2,8-dihydroxyadenine in the urine, normalized for urine concentration, is above the upper limit of normal.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
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.
Elevated circulating creatinine concentration
MedGen UID:
148579
Concept ID:
C0700225
Finding
An increased amount of creatinine in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAdenine phosphoribosyltransferase deficiency

Professional guidelines

PubMed

Thorsteinsdottir M, Thorsteinsdottir UA, Eiriksson FF, Runolfsdottir HL, Agustsdottir IM, Oddsdottir S, Sigurdsson BB, Hardarson HK, Kamble NR, Sigurdsson ST, Edvardsson VO, Palsson R
J Chromatogr B Analyt Technol Biomed Life Sci 2016 Nov 15;1036-1037:170-177. Epub 2016 Sep 14 doi: 10.1016/j.jchromb.2016.09.018. PMID: 27770717Free PMC Article
Bollée G, Dollinger C, Boutaud L, Guillemot D, Bensman A, Harambat J, Deteix P, Daudon M, Knebelmann B, Ceballos-Picot I
J Am Soc Nephrol 2010 Apr;21(4):679-88. Epub 2010 Feb 11 doi: 10.1681/ASN.2009080808. PMID: 20150536Free PMC Article
Edvardsson V, Palsson R, Olafsson I, Hjaltadottir G, Laxdal T
Am J Kidney Dis 2001 Sep;38(3):473-80. doi: 10.1053/ajkd.2001.26826. PMID: 11532677

Recent clinical studies

Etiology

Runolfsdottir HL, Palsson R, Agustsdottir IMS, Indridason OS, Li J, Dao M, Knebelmann B, Milliner DS, Edvardsson VO
Transplantation 2020 Oct;104(10):2120-2128. doi: 10.1097/TP.0000000000003088. PMID: 31880754Free PMC Article
Veser J, Özsoy M, Seitz C
Curr Opin Urol 2018 Sep;28(5):414-419. doi: 10.1097/MOU.0000000000000522. PMID: 29957682
Rumsby G
Int J Surg 2016 Dec;36(Pt D):590-595. Epub 2016 Nov 10 doi: 10.1016/j.ijsu.2016.11.015. PMID: 27838384
Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO
Am J Kidney Dis 2016 Mar;67(3):431-8. Epub 2015 Dec 25 doi: 10.1053/j.ajkd.2015.10.023. PMID: 26724837Free PMC Article
Boss GR, Seegmiller JE
Annu Rev Genet 1982;16:297-328. doi: 10.1146/annurev.ge.16.120182.001501. PMID: 6297375

Diagnosis

Nourié N, Nassereddine H, Azar H
Nephron 2021;145(5):503-507. Epub 2021 May 27 doi: 10.1159/000516281. PMID: 34044400
Veser J, Özsoy M, Seitz C
Curr Opin Urol 2018 Sep;28(5):414-419. doi: 10.1097/MOU.0000000000000522. PMID: 29957682
Becker GJ, Garigali G, Fogazzi GB
Am J Kidney Dis 2016 Jun;67(6):954-64. Epub 2016 Jan 22 doi: 10.1053/j.ajkd.2015.11.011. PMID: 26806004
Valaperta R, Rizzo V, Lombardi F, Verdelli C, Piccoli M, Ghiroldi A, Creo P, Colombo A, Valisi M, Margiotta E, Panella R, Costa E
BMC Nephrol 2014 Jul 1;15:102. doi: 10.1186/1471-2369-15-102. PMID: 24986359Free PMC Article
Bollée G, Harambat J, Bensman A, Knebelmann B, Daudon M, Ceballos-Picot I
Clin J Am Soc Nephrol 2012 Sep;7(9):1521-7. Epub 2012 Jun 14 doi: 10.2215/CJN.02320312. PMID: 22700886

Therapy

Nourié N, Nassereddine H, Azar H
Nephron 2021;145(5):503-507. Epub 2021 May 27 doi: 10.1159/000516281. PMID: 34044400
Runolfsdottir HL, Palsson R, Agustsdottir IMS, Indridason OS, Li J, Dao M, Knebelmann B, Milliner DS, Edvardsson VO
Transplantation 2020 Oct;104(10):2120-2128. doi: 10.1097/TP.0000000000003088. PMID: 31880754Free PMC Article
Parikh MD, Konnur A, Gang S
Saudi J Kidney Dis Transpl 2019 May-Jun;30(3):723-725. doi: 10.4103/1319-2442.261357. PMID: 31249241
Kumar G, AlAni RR
Saudi J Kidney Dis Transpl 2018 Sep-Oct;29(5):1203-1206. doi: 10.4103/1319-2442.243955. PMID: 30381520
Bollée G, Harambat J, Bensman A, Knebelmann B, Daudon M, Ceballos-Picot I
Clin J Am Soc Nephrol 2012 Sep;7(9):1521-7. Epub 2012 Jun 14 doi: 10.2215/CJN.02320312. PMID: 22700886

Prognosis

Assadi F, Faghihi T
Nephrology (Carlton) 2024 Dec;29(12):781-790. Epub 2024 Nov 5 doi: 10.1111/nep.14373. PMID: 39497582
Nourié N, Nassereddine H, Azar H
Nephron 2021;145(5):503-507. Epub 2021 May 27 doi: 10.1159/000516281. PMID: 34044400
Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO
Am J Kidney Dis 2016 Mar;67(3):431-8. Epub 2015 Dec 25 doi: 10.1053/j.ajkd.2015.10.023. PMID: 26724837Free PMC Article
Bollée G, Harambat J, Bensman A, Knebelmann B, Daudon M, Ceballos-Picot I
Clin J Am Soc Nephrol 2012 Sep;7(9):1521-7. Epub 2012 Jun 14 doi: 10.2215/CJN.02320312. PMID: 22700886
Takeuchi H, Kaneko Y, Fujita J, Yoshida O
J Urol 1993 Apr;149(4):824-6. doi: 10.1016/s0022-5347(17)36222-5. PMID: 8455250

Clinical prediction guides

Nanmoku K, Kurosawa A, Shinzato T, Shimizu T, Kimura T, Yagisawa T
Intern Med 2017;56(11):1387-1391. Epub 2017 Jun 1 doi: 10.2169/internalmedicine.56.8142. PMID: 28566603Free PMC Article
Runolfsdottir HL, Palsson R, Agustsdottir IM, Indridason OS, Edvardsson VO
Am J Kidney Dis 2016 Mar;67(3):431-8. Epub 2015 Dec 25 doi: 10.1053/j.ajkd.2015.10.023. PMID: 26724837Free PMC Article
Bollée G, Harambat J, Bensman A, Knebelmann B, Daudon M, Ceballos-Picot I
Clin J Am Soc Nephrol 2012 Sep;7(9):1521-7. Epub 2012 Jun 14 doi: 10.2215/CJN.02320312. PMID: 22700886
Liang L, Chen J, Vittal R, Selvanayagam ZE, McAteer JA, Deng L, Tischfield J, Chin KV, Sahota A
Nephron Physiol 2006;103(1):p53-62. Epub 2005 Dec 21 doi: 10.1159/000090503. PMID: 16374038
Gupta PK, Sahota A, Boyadjiev SA, Bye S, Shao C, O'Neill JP, Hunter TC, Albertini RJ, Stambrook PJ, Tischfield JA
Cancer Res 1997 Mar 15;57(6):1188-93. PMID: 9067291

Recent systematic reviews

Rashid I, Verma A, Tiwari P, D'Cruz S
J Bras Nefrol 2022 Jul-Sep;44(3):403-416. doi: 10.1590/2175-8239-JBN-2021-0283en. PMID: 35635787Free PMC Article

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