2,8 dihydroxy-adenine urolithiasis: Difference between revisions
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==Overview== | ==Overview== | ||
2,8 dihydroxy-adenine urolithiasis is a genetic disorder | 2,8 dihydroxy-adenine urolithiasis is a genetic disorder in which deficiency of the enzyme [[adenine phosphoribosyltransferase]] leads to [[nephrolithiasis]], permanent kidney damage and eventually [[chronic renal failure]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
===Genetics=== | ===Genetics=== | ||
* | *The disease is an [[autosomal recessive disorder]] associated with a [[mutation]] in the enzyme [[adenine phosphoribosyltransferase]]. | ||
* | *The enzyme catalyzes the formation of [[AMP]] from [[adenine]] and [[phosphoribosylpyrophosphate]]. It can act as a salvage enzyme to recycle [[adenine]] into [[nucleic acids]]. | ||
*Deficiency of this enzyme leads to excess formation and hyperexcretion of 2,8 dihydroxy adenine (DHA) into [[urine]]. | *Deficiency of this enzyme leads to excess formation and hyperexcretion of 2,8 dihydroxy adenine (DHA) into [[urine]]. | ||
*Low solubility of DHA results in precipitation of this compound and | *Low solubility of DHA results in precipitation of this compound and the formation of crystals and stones. | ||
==Epidemiology and Demographics== | |||
*More than 300 individuals with this disorder have been reported so far, out of which two thirds were from Japan, and a substantial number from France and Iceland. | |||
*The estimated prevalence of APRT deficiency is 0.5 to 1 per 100,000 in the Caucasian population, 0.25 to 0.5 per 100,000 in the Japanese population and in Iceland the estimated point prevalence is 8.9/100,000 <ref name="pmid3193517">{{cite journal |author=Kamatani N, Sonoda T, Nishioka K |title=Distribution of patients with 2,8-dihydroxyadenine urolithiasis and adenine phosphoribosyltransferase deficiency in Japan |journal=[[The Journal of Urology]] |volume=140 |issue=6 |pages=1470–2 |year=1988 |month=December |pmid=3193517 |doi= |url=}}</ref> <ref name="pmid11532677">{{cite journal |author=Edvardsson V, Palsson R, Olafsson I, Hjaltadottir G, Laxdal T |title=Clinical features and genotype of adenine phosphoribosyltransferase deficiency in iceland |journal=[[American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation]] |volume=38 |issue=3 |pages=473–80 |year=2001 |month=September |pmid=11532677 |doi= |url=}}</ref> | |||
==Natural History, Complications and Prognosis== | |||
===Complications=== | |||
*[[Nephrolithiasis]] | |||
*[[Chronic renal failure]] | |||
==Diagnosis== | |||
===Symptoms=== | |||
*Associated with [[renal stones]]: | |||
**[[Colic]]ky pain | |||
**[[Hematuria]] | |||
**[[Dysuria]] | |||
**[[Oliguria]] | |||
**Reddish brown diaper spots in younger children | |||
*Associated with [[chronic renal failure]]: | |||
**[[Nausea]]/ [[Vomiting]] | |||
**[[Weakness]] and [[fatigue]] | |||
**[[Anorexia]] and [[weight loss]] | |||
*Occasionally, patients may also complain of eye discomfort. | |||
===Physical examination=== | |||
====Appearance of the Patient==== | |||
*Patient may appear to be in distress from [[colicky flank pain]] and/or [[uremia]] | |||
====Vital Signs==== | |||
In advanced cases with signs of [[chronic renal failure]], | |||
*[[Blood pressure]] may be elevated. | |||
*Patient may be [[Tachypnea|tachypneic]] from [[metabolic acidosis]] associated with [[uremia]]. | |||
====Eyes==== | |||
*[[Conjunctiva]] may appear [[Hyperemia|hyperemic]] from eye discomfort. | |||
====Heart==== | |||
*Patients with renal compromise may have a ventricular [[heave]]. | |||
*Auscultation | |||
**S4 may be heard | |||
**[[Pericardial friction rub]] in those with chronic [[uremia]]. | |||
====Lungs==== | |||
*Auscultation | |||
**[[Crackles]] | |||
**Decreased breath sounds from [[pulmonary edema]] in those who develop [[chronic renal failure]]. | |||
===Laboratory Findings=== | |||
Early recognition and treatment of APRT deficiency is crucial in preventing irreversible damage to the [[kidneys]]. | |||
====Urinalysis==== | |||
*Stone analysis: 2,8 DHA crystals are readily detectable in the urine. | |||
*[[Crystalluria]]: The small and medium sized crystals have a central maltese cross pattern on polarized light microscopy whereas the large crystals do not as they are impermeable to light . | |||
====Blood tests==== | |||
*APRT activity in hemolysates of erythrocytes. | |||
====X ray==== | |||
*2,8 Dihydro adenine stones are radiolucent, hence not detected on X-ray films. | |||
====CT==== | |||
*[[Renal stones]] are easily detectable on [[CT scan]]. | |||
====Ultrasonography==== | |||
*[[Ultrasonography]] is highly sensitive for detecting [[renal stones]]. | |||
====Spectrophotometry and Crystallography==== | |||
*Easily differentiates 2,8 DHA stones from [[uric acid]] stones. | |||
====Genetic Testing==== | |||
*Identifying mutations in both copies of the APRT gene. | |||
==Treatment== | |||
===Pharmacotherapy=== | |||
*[[Allopurinol]]: 5-10 mg/kg/day (maximum dose of 600-800 mg/day). Side effects include skin [[rash]] and [[gastrointestinal intolerance]], [[hypersensitivity]]. | |||
*Patients who do not tolerate [[allopurinol]], febuxostat (a xanthine oxidase inhibitor) or oxypurinol (a xanthine dehydrogenase inhibitor) should be considered. | |||
===Patient Education=== | |||
*Plenty of fluids | |||
*Dietary [[purine]] restriction. | |||
===Follow up=== | |||
*Patients treated with [[allopurinol]] can be followed up by monitoring urine microscopy. | |||
===Surgery and Device based therapy=== | |||
*Approximately 30% of patients require intervention for stone removal | |||
**Extracorporeal shock-wave lithotripsy, | |||
**Lithotomy and | |||
**Endourological procedures | |||
==References== | |||
{{reflist|2}} | |||
==See also== | ==See also== | ||
* [[Adenine phosphoribosyltransferase]] | * [[Adenine phosphoribosyltransferase]] | ||
{{genetic-disorder-stub}} | {{genetic-disorder-stub}} | ||
{{WikiDoc Help Menu}} | {{WikiDoc Help Menu}} | ||
{{WikiDoc Sources}} | {{WikiDoc Sources}} | ||
[[Category:Genetic disorders]] | |||
Latest revision as of 15:56, 6 August 2012
| 2,8 dihydroxy-adenine urolithiasis | |
| ICD-10 | E79 |
|---|---|
| ICD-9 | 277.2 |
| OMIM | 102600 |
| DiseasesDB | 32632 |
File:Autorecessive.svg Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Synonyms and keywords: Adenine phosphoribosyltransferase deficiency; AMP pyrophorylase deficiency; APRT deficiency
Overview
2,8 dihydroxy-adenine urolithiasis is a genetic disorder in which deficiency of the enzyme adenine phosphoribosyltransferase leads to nephrolithiasis, permanent kidney damage and eventually chronic renal failure.
Pathophysiology
Genetics
- The disease is an autosomal recessive disorder associated with a mutation in the enzyme adenine phosphoribosyltransferase.
- The enzyme catalyzes the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme to recycle adenine into nucleic acids.
- Deficiency of this enzyme leads to excess formation and hyperexcretion of 2,8 dihydroxy adenine (DHA) into urine.
- Low solubility of DHA results in precipitation of this compound and the formation of crystals and stones.
Epidemiology and Demographics
- More than 300 individuals with this disorder have been reported so far, out of which two thirds were from Japan, and a substantial number from France and Iceland.
- The estimated prevalence of APRT deficiency is 0.5 to 1 per 100,000 in the Caucasian population, 0.25 to 0.5 per 100,000 in the Japanese population and in Iceland the estimated point prevalence is 8.9/100,000 [1] [2]
Natural History, Complications and Prognosis
Complications
Diagnosis
Symptoms
- Associated with renal stones:
- Associated with chronic renal failure:
- Occasionally, patients may also complain of eye discomfort.
Physical examination
Appearance of the Patient
- Patient may appear to be in distress from colicky flank pain and/or uremia
Vital Signs
In advanced cases with signs of chronic renal failure,
- Blood pressure may be elevated.
- Patient may be tachypneic from metabolic acidosis associated with uremia.
Eyes
- Conjunctiva may appear hyperemic from eye discomfort.
Heart
- Patients with renal compromise may have a ventricular heave.
- Auscultation
- S4 may be heard
- Pericardial friction rub in those with chronic uremia.
Lungs
- Auscultation
- Crackles
- Decreased breath sounds from pulmonary edema in those who develop chronic renal failure.
Laboratory Findings
Early recognition and treatment of APRT deficiency is crucial in preventing irreversible damage to the kidneys.
Urinalysis
- Stone analysis: 2,8 DHA crystals are readily detectable in the urine.
- Crystalluria: The small and medium sized crystals have a central maltese cross pattern on polarized light microscopy whereas the large crystals do not as they are impermeable to light .
Blood tests
- APRT activity in hemolysates of erythrocytes.
X ray
- 2,8 Dihydro adenine stones are radiolucent, hence not detected on X-ray films.
CT
- Renal stones are easily detectable on CT scan.
Ultrasonography
- Ultrasonography is highly sensitive for detecting renal stones.
Spectrophotometry and Crystallography
- Easily differentiates 2,8 DHA stones from uric acid stones.
Genetic Testing
- Identifying mutations in both copies of the APRT gene.
Treatment
Pharmacotherapy
- Allopurinol: 5-10 mg/kg/day (maximum dose of 600-800 mg/day). Side effects include skin rash and gastrointestinal intolerance, hypersensitivity.
- Patients who do not tolerate allopurinol, febuxostat (a xanthine oxidase inhibitor) or oxypurinol (a xanthine dehydrogenase inhibitor) should be considered.
Patient Education
- Plenty of fluids
- Dietary purine restriction.
Follow up
- Patients treated with allopurinol can be followed up by monitoring urine microscopy.
Surgery and Device based therapy
- Approximately 30% of patients require intervention for stone removal
- Extracorporeal shock-wave lithotripsy,
- Lithotomy and
- Endourological procedures
References
- ↑ Kamatani N, Sonoda T, Nishioka K (1988). "Distribution of patients with 2,8-dihydroxyadenine urolithiasis and adenine phosphoribosyltransferase deficiency in Japan". The Journal of Urology. 140 (6): 1470–2. PMID 3193517. Unknown parameter
|month=ignored (help) - ↑ Edvardsson V, Palsson R, Olafsson I, Hjaltadottir G, Laxdal T (2001). "Clinical features and genotype of adenine phosphoribosyltransferase deficiency in iceland". American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 38 (3): 473–80. PMID 11532677. Unknown parameter
|month=ignored (help)