What are the other Names for this Condition? (Also known as/Synonyms)

• 2,8-Dihydroxyadenine Urolithiasis
• APRT Deficiency Disorder
• DHA Crystalline Nephropathy

What is Adenine Phosphoribosyltransferase Deficiency Disorder? (Definition/Background Information)

• Adenine Phosphoribosyltransferase (APRT) Deficiency Disorder is a genetic disorder that is more commonly found in certain Icelandic, Japanese, and some European populations
• Mutations in the APRT gene cause the condition, wherein the enzyme adenine phosphoribosyltransferase is impaired. This leads to the formation of 2,8- dihydroxyadenine (2,8-DHA), which is toxic to the cells and crystallizes in urine, as well as in the urinary tract, leading to the characteristic symptoms of the disorder
• The onset of symptoms could occur during infancy, childhood, or adulthood. It is reported that 15-20% of the affected individuals may remain asymptomatic
• The characteristic symptoms of APRT Deficiency Disorder include reddish brown crystalline substance in the diapers of infants, repeated kidney stone formation in children and adults, nausea, fever, vomiting, and pain during urination
• Chronic kidney disease and renal failure are some of the potential complications of this deficiency disorder, which can be diagnosed via physical examination, evaluation of family history, assessment of symptoms, examination of the urine for crystals, blood tests, and genetic screenings 
• Following a low-purine diet (such as eggs, low-fat foods, and some vegetables), increased fluid intake, and taking medication for reducing uric acid are some of the treatment options available to the individuals affected by Adenine Phosphoribosyltransferase Deficiency Disorder
• Since the disorder is genetic in nature, currently there are no methods to prevent it from occurring. Although, expecting parents may benefit from genetic testing and counselling, if there is a family history of the disorder. Avoiding a high-purine diet (that includes certain meat types, seafood, and alcohol) may be recommended to reduce the severity of symptoms in those affected
• If diagnosed early and treated promptly, the prognosis of Adenine Phosphoribosyltransferase Deficiency is good. However, misdiagnosis and/or a lack of treatment can lead to both renal malfunction and renal failure

Who gets Adenine Phosphoribosyltransferase Deficiency Disorder? (Age and Sex Distribution)

• Adenine Phosphoribosyltransferase Deficiency Disorder is reported to occur predominantly in some Japanese, Icelandic, and European populations
  • The estimated prevalence in Japan is 1 in 27,000 individuals
  • In Iceland, one in every 15,000 individuals is affected
  • While the condition appears rarer in Caucasian Europeans, with one in every 50,000-100,000 people reported as affected; the carrier status of the disorder in Caucasian population is estimated to be between 1 in every 100-250 individual
• APRT deficiency may affect both the male and female genders
• The onset of disease symptoms can occur with equal probability in childhood or adulthood, with symptoms observed in infants as young as 5 months old

What are the Risk Factors for Adenine Phosphoribosyltransferase Deficiency Disorder? (Predisposing Factors)

• Since Adenine Phosphoribosyltransferase Deficiency Disorder is an inherited disorder, having a family history of the condition is the only major risk factor known for developing the same

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Adenine Phosphoribosyltransferase Deficiency Disorder? (Etiology)

• Adenine Phosphoribosyltransferase Deficiency Disorder is caused by mutations in the APRT gene
  • The gene codes for an enzyme, adenine phosphoribosyltransferase, which catalyzes the conversion of adenine to adenosine monophosphate (AMP). Adenine is one of the building blocks of DNA and gets converted to AMP when there is a demand for energy in the cells
  • Mutations in the APRT gene lead to impaired enzyme function. Instead of being used to generate AMP molecules, adenine gets converted to 2,8-dihydroxyadenine (2,8-DHA)
  • 2,8-DHA is known to be toxic to the kidneys and crystallizes in the urine, leading to the formation of stones and consequent symptoms of the disorder
• APRT Deficiency Disorder is inherited in an autosomal recessive manner, in which an individual needs to carry both copies of the APRT gene being defective, in order to develop the condition. The parents of such an individual will carry one defective copy of the gene and generally not shown any symptom of the disorder

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

What are the Signs and Symptoms of Adenine Phosphoribosyltransferase Deficiency Disorder?

The main signs and symptoms of Adenine Phosphoribosyltransferase Deficiency Disorder include:

• In infancy: Reddish brown stain in the baby’s diapers, which develops as a result of the baby passing the kidney stones in urine
• In childhood and adulthood:
  • Repeated kidney stone formations, affecting kidney function
  • Pain during urination, abdominal pain
  • Difficulty releasing urine
  • Fever
  • Nausea, vomiting
  • Frequent urinary tract infections
  • Blood in the urine, a condition known as hematuria
  • A condition known as 2,8-DHA nephropathy, a progressive worsening of kidney function. In many individuals, the condition may be undiagnosed resulting in progressive kidney dysfunction

Note: About 15-20% of individuals with the condition are symptomless. Additionally, the severity of the condition is known to vary among individuals, even if they belong to the same family.

How is Adenine Phosphoribosyltransferase Deficiency Disorder Diagnosed?

For an accurate diagnosis of Adenine Phosphoribosyltransferase Deficiency Disorder, the following may be performed: 

• A physical examination
• An evaluation of family medical history
• An assessment of symptoms
• Detection of 2,8-DHA crystals, using techniques such as
  • Examination of crystalline urine deposits under a microscope
  • Infrared spectrometry of crystals
  • X-ray crystallography of urinary crystals
  • Biopsy of kidney tissue, if necessary
• Thin-layer chromatography (TLC) of urine to check for adenine in urine
• Analysis of erythrocyte lysates for determining adenine phosphoribosyltransferase activity level
• Genetic testing, if required for family screening

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Adenine Phosphoribosyltransferase Deficiency Disorder?

Some of the potential complications associated with Adenine Phosphoribosyltransferase Deficiency Disorder are:

• Chronic renal failure in some individuals
• End-stage renal disease (ESRD), if the condition remains undiagnosed for a long duration of time

How is Adenine Phosphoribosyltransferase Deficiency Disorder Treated?

The treatment options for Adenine Phosphoribosyltransferase Deficiency Disorder may include:

• Increased hydration
• Resorting to a low purine diet (avoiding organ meats and fatty foods, limiting liquor, and increasing fruits and vegetables)
• Taking prescription drugs that reduces uric acid (known as allopurinol)
• Kidney transplantation, in case APRT Deficiency Disorder is misdiagnosed and evolves into kidney failure

How can Adenine Phosphoribosyltransferase Deficiency Disorder be Prevented?

• Currently, there are no specific methods or guidelines to prevent Adenine Phosphoribosyltransferase Deficiency Disorder, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Adenine Phosphoribosyltransferase Deficiency Disorder
• Asymptomatic individuals with the condition also need to undergo periodic testing to assess their condition. Such individuals may require medication to avoid developing symptoms
• Although APRT Deficiency Disorder is not preventable, the symptoms may be delayed or decreased by adhering to a purine-free diet (such as bread, cake, low-fat milk and cheese, eggs, nuts, fruits, etc.) per the recommendations of a healthcare professional

What is the Prognosis of Adenine Phosphoribosyltransferase Deficiency Disorder? (Outcome/Resolutions)

• The prognosis for Adenine Phosphoribosyltransferase Deficiency Disorder is reported to be favorable, with early and accurate diagnosis, followed by proper and continued treatment
• Kidney malfunction or kidney failure can occur without proper diagnosis/treatment

Additional and Relevant Useful Information for Adenine Phosphoribosyltransferase Deficiency Disorder:

Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:

http://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/