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| {{Infobox medical condition (new)
| | == Adenine Phosphoribosyltransferase Deficiency == |
| | name = Adenine phosphoribosyltransferase deficiency
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| | image = Dihydroxyadenine.png
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| | caption = Dihydroxyadenine, an insoluble purine
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| | synonyms = '''APRT deficiency''' or '''2,8 Dihydroxyadenine urolithiasis'''
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| '''Adenine phosphoribosyltransferase deficiency''' is an [[autosome|autosomal]] [[dominance (genetics)|recessive]]<ref name="pmid8976113">{{cite journal |pmid=8976113 |date=December 1996|author =Kamatani, N |title=Adenine phosphoribosyltransferase(APRT) deficiency |volume=54 |issue=12 |pages=3321–7 |issn=0047-1852 |journal=Nippon Rinsho. Japanese Journal of Clinical Medicine |url=http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+315-30-0 |format=Free full text}}</ref> [[metabolic disorder]] associated with a mutation in the enzyme [[adenine phosphoribosyltransferase]].<ref name="pmid8825602">{{cite journal |doi=10.1111/j.1399-0004.1995.tb04098.x |pmid=8825602 |date=November 1995|author1=Terai, C |author2=Hakoda, M |author3=Yamanaka, H |author4=Kamatani, N |author5=Okai, M |author6=Takahashi, F |author7=Kashiwazaki, S |title=Adenine phosphoribosyltransferase deficiency identified by urinary sediment analysis: cellular and molecular confirmation |volume=48 |issue=5 |pages=246–50 |issn=0009-9163 |journal=Clinical Genetics}}</ref> | | '''Adenine phosphoribosyltransferase deficiency''' (APRT deficiency) is a rare [[autosomal recessive disorder]] that affects the body's ability to process adenine, a component of [[nucleic acids]]. This metabolic disorder leads to the accumulation of 2,8-dihydroxyadenine (DHA) in the urine, which can cause [[kidney stones]] and [[renal failure]]. |
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| == Signs and symptoms == | | == Pathophysiology == |
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| Most patients with APRT deficiency have repeated episodes of kidney stones that are not detected by a conventional x-ray study. However, all stones are easily detected by other medical imaging methods such as ultrasound or computerized tomography (CT) scan. A minority of patients develop symptoms of kidney failure. Kidney stones are often associated with severe loin or abdominal pain. Symptoms associated with kidney failure are largely nonspecific such as increased fatigue and weakness, poor appetite, and weight loss. Children with the disease may have similar symptoms as adults. In young children, APRT deficiency can cause reddish-brown diaper spots.{{citation needed|date=June 2017}}
| | APRT deficiency is caused by mutations in the [[APRT gene]], which encodes the enzyme adenine phosphoribosyltransferase. This enzyme is responsible for the conversion of adenine to adenosine monophosphate (AMP) in the [[purine salvage pathway]]. When APRT is deficient or non-functional, adenine is instead converted to 2,8-dihydroxyadenine, a poorly soluble compound that precipitates in the urinary tract, leading to stone formation and potential kidney damage. |
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| == Genetics == | | == Clinical Presentation == |
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| [[Image:Autorecessive.svg|thumb|right|Adenine phosphoribosyltransferase deficiency has an autosomal recessive pattern of [[heredity|inheritance]].]] | | Patients with APRT deficiency may present with symptoms related to kidney stones, such as [[hematuria]], [[flank pain]], and urinary tract infections. In severe cases, chronic kidney disease or acute renal failure may occur due to the accumulation of DHA crystals in the renal tubules. |
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| APRT deficiency is inherited in an autosomal recessive manner.<ref name="pmid8976113"/> This means the defective gene responsible for the disorder is located on an [[autosome]], and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both [[genetic carrier|carry]] one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
| | == Diagnosis == |
| ===Characteristics=== | |
| The disorder results in accumulation of the insoluble [[purine]] [[2,8-dihydroxyadenine]].<ref name="pmid11138609">{{cite journal |pmid=11138609 |year=2000 |month= |author1=Funato, T |author2=Nishiyama, Y |author3=Ioritani, N |author4=Matsuki, R |author5=Yoshida, K |author6=Kaku, M |author7=Sasaki, T |author8=Ideguchi, H |author9=Ono, J |title=Detection of mutations in adenine phosphoribosyltransferase (APRT) deficiency using the LightCycler system |volume=14 |issue=6 |pages=274–9 |issn=0887-8013 |journal=Journal of Clinical Laboratory Analysis |doi=10.1002/1098-2825(20001212)14:6<274::AID-JCLA5>3.0.CO;2-2|pmc=6808163 }}</ref>
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| It can result in [[nephrolithiasis]] (kidney stones), [[acute renal failure]] and permanent [[kidney]] damage.
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| More than 300 individuals with this disease have been reported world-wide but it is not known how common this medical problem truly is. Patients with the disease deficiency lack the enzyme adenine phosphoribosyltransferase and therefore have difficulties breaking down dietary substances called purines, resulting in accumulation of a compound called 2,8-dihydroxyadenine (2,8-DHA) that is excreted by the kidneys. Up to 70% of affected patients, have red hair or relatives with this hair color.
| | The diagnosis of APRT deficiency is typically confirmed through genetic testing to identify mutations in the APRT gene. Additionally, the presence of DHA crystals in the urine can be detected using specialized microscopy techniques. Urinary DHA levels can also be measured to support the diagnosis. |
| ==Diagnosis==
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| Adenine phosphoribosyltransferase (APRT) deficiency (also known as 2,8-dihydroxyadeninuria) should be suspected in individuals with the following clinical, radiographic, laboratory, and pathology findings.
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| '''Clinical manifestations'''
| | == Treatment == |
| * Kidney stone disease and renal [[colic]]
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| * [[Chronic kidney disease]] (CKD)
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| * Crystal [[nephropathy]] (confirmed by kidney [[biopsy]])
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| * Reddish-brown diaper stain in infants and young children
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| * Allograft dysfunction following kidney transplantation
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| '''Radiographic findings'''
| | Management of APRT deficiency involves reducing the production of DHA and preventing stone formation. This can be achieved through dietary modifications, such as reducing purine intake, and the use of medications like [[allopurinol]] or [[febuxostat]], which inhibit xanthine oxidase and decrease the production of DHA. Adequate hydration is also crucial to prevent stone formation. |
| * Radiolucent kidney stones, detected by [[ultrasound]] or [[computed tomography]] (CT). Stones are not seen on a plain abdominal x-ray.
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| * Ultrasound examination frequently demonstrates increased echogenicity of the kidneys.
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| '''Laboratory findings'''
| | == Prognosis == |
| * Urine [[microscopy]]. The round and brown DHA crystals can usually be detected by urine microscopy . Small and medium-sized DHA crystals display a central Maltese cross pattern when viewed by [[polarized light microscopy]] , while larger crystal aggregates do not as they are impermeable to light.
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| '''Kidney stone analysis. '''Analysis of DHA crystals and kidney stone material using infrared or [[ultraviolet spectrophotometry]] (at both acidic and alkaline pH) and/or [[x-ray crystallography]] differentiates DHA from [[uric acid]] and [[xanthine]], which also form radiolucent stones. Although stones in persons with APRT deficiency are predominantly composed of DHA, they may contain trace amounts of other minerals.
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| * Kidney stone analysis using the above techniques is dependent on skilled personnel and, thus, cannot be used to establish a diagnosis of APRT deficiency .
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| * Stone analysis employing standard chemical and thermogravimetric methods does not distinguish DHA from other purines (e.g., uric acid) and is not recommended.
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| The diagnosis of APRT deficiency is established in a proband with absent APRT enzyme activity in red cell lysates or biallelic pathogenic variants in APRT identified by molecular [[genetic testing]].
| | With appropriate treatment and management, individuals with APRT deficiency can lead normal lives. However, if left untreated, the condition can lead to significant renal damage and complications. |
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| ==Treatment== | | == Related Pages == |
| Treatment with the xanthine oxidoreductase inhibitors (XOR; [[xanthine dehydrogenase]]/oxidase) [[allopurinol]] or [[febuxostat]] can improve kidney function, even in individuals with advanced CKD. The prescribed dose of allopurinol and febuxostat should not routinely be reduced in affected individuals who have impaired kidney function. Ample fluid intake is advised. Surgical management of DHA [[nephrolithiasis]] is the same as for other types of kidney stones. ESRD is treated with [[dialysis]] and [[kidney transplantation]]. Even after kidney transplantation, treatment with an XOR is recommended.
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| '''Agents/circumstances to avoid:''' [[Azathioprine]] and [[mercaptopurine]] should not be given to individuals taking either allopurinol or febuxostat.
| | * [[Purine metabolism disorders]] |
| | * [[Kidney stone disease]] |
| | * [[Genetic disorders]] |
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| ==References==
| | [[Category:Genetic disorders]] |
| {{reflist}}
| | [[Category:Metabolic disorders]] |
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| == External links ==
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| {{Medical resources
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| | DiseasesDB = 32632
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| | ICD10 = {{ICD10|E|79||e|70}}
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| | ICD9 = {{ICD9|277.2}}
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| | ICDO =
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| | OMIM = 102600
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| | eMedicineSubj =
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| | eMedicineTopic =
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| | Orphanet = 976
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| }}
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| *{{RareDiseases|546|Adenine phosphoribosyltransferase deficiency}}
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| {{Purine, pyrimidine, porphyrin, bilirubin metabolic pathology}}
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| [[Category:Autosomal recessive disorders]] | |
| [[Category:Kidney diseases]] | | [[Category:Kidney diseases]] |
| [[Category:Inborn errors of purine-pyrimidine metabolism]]
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Adenine Phosphoribosyltransferase Deficiency
Adenine phosphoribosyltransferase deficiency (APRT deficiency) is a rare autosomal recessive disorder that affects the body's ability to process adenine, a component of nucleic acids. This metabolic disorder leads to the accumulation of 2,8-dihydroxyadenine (DHA) in the urine, which can cause kidney stones and renal failure.
Pathophysiology
APRT deficiency is caused by mutations in the APRT gene, which encodes the enzyme adenine phosphoribosyltransferase. This enzyme is responsible for the conversion of adenine to adenosine monophosphate (AMP) in the purine salvage pathway. When APRT is deficient or non-functional, adenine is instead converted to 2,8-dihydroxyadenine, a poorly soluble compound that precipitates in the urinary tract, leading to stone formation and potential kidney damage.
Clinical Presentation
Patients with APRT deficiency may present with symptoms related to kidney stones, such as hematuria, flank pain, and urinary tract infections. In severe cases, chronic kidney disease or acute renal failure may occur due to the accumulation of DHA crystals in the renal tubules.
Diagnosis
The diagnosis of APRT deficiency is typically confirmed through genetic testing to identify mutations in the APRT gene. Additionally, the presence of DHA crystals in the urine can be detected using specialized microscopy techniques. Urinary DHA levels can also be measured to support the diagnosis.
Treatment
Management of APRT deficiency involves reducing the production of DHA and preventing stone formation. This can be achieved through dietary modifications, such as reducing purine intake, and the use of medications like allopurinol or febuxostat, which inhibit xanthine oxidase and decrease the production of DHA. Adequate hydration is also crucial to prevent stone formation.
Prognosis
With appropriate treatment and management, individuals with APRT deficiency can lead normal lives. However, if left untreated, the condition can lead to significant renal damage and complications.
Related Pages
