Clinical Guidance

No genotype-phenotype correlations have been established; clinical features are known to vary greatly among individuals with the same pathogenic variants .

Source: GeneReviews — "Adenine Phosphoribosyltransferase Deficiency"

Diagnostic Criteria

Suggestive Findings

Adenine phosphoribosyltransferase (APRT) deficiency (also known as 2,8-dihydroxyadeninuria) should be suspected in individuals with the following clinical, radiographic, laboratory, and pathology findings [, , , ].

Clinical manifestations

• Kidney stone disease and renal colic

• Chronic kidney disease (CKD)

• Crystal nephropathy (confirmed by kidney biopsy; see Pathology)

• Reddish-brown diaper stain in infants and young children

• Allograft dysfunction following kidney transplantation

Radiographic findings

• Radiolucent kidney stones, detected by ultrasound or computed tomography (CT). Stones are not seen on a plain abdominal x-ray.

• Ultrasound examination frequently demonstrates increased echogenicity of the kidneys.

Laboratory findings

Source: GeneReviews — "Adenine Phosphoribosyltransferase Deficiency"

Differential Diagnosis

Differential diagnosis of APRT deficiency includes other known causes of radiolucent kidney stones such as uric acid nephrolithiasis (OMIM 605990) and xanthinuria (OMIM PS278300). The diagnosis of APRT deficiency should be considered in all individuals with chronic kidney disease or kidney failure, particularly in those with renal histopathologic features of crystal nephropathy, even in the absence of a history of nephrolithiasis. Pathologists and physicians must be aware that kidney biopsy findings in persons with APRT deficiency may have a similar appearance to and be confused with those of primary hyperoxaluria type 1, type 2, and type 3 .

Source: GeneReviews — "Adenine Phosphoribosyltransferase Deficiency"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with adenine phosphoribosyltransferase (APRT) deficiency, the evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with APRT Deficiency

Source: GeneReviews — "Adenine Phosphoribosyltransferase Deficiency"

Clinical Guidance

Azathioprine and mercaptopurine should be avoided by individuals taking XOR inhibitors (allopurinol or febuxostat). Inhibition of xanthine oxidase may cause increased plasma concentrations of azathioprine or mercaptopurine, leading to toxicity.

Source: GeneReviews — "Adenine Phosphoribosyltransferase Deficiency"

Surveillance Guidelines

No consensus surveillance guidelines have been established.

Table 6.

Recommended Surveillance for Individuals with APRT Deficiency

System/Concern | Evaluation | Frequency

Renal

| Measurement of eGFR derived from serum creatinine /or serum cystatin C | Every 6-12 mos or as clinically indicated

Urine microscopy for assessment of DHA crystalluria1,2,3 if direct DHA measurements not available4

Renal ultrasound5 | Periodically

Other

| Assess medication compliance. | At least annually

eGFR = estimated glomerular filtration rate

1. Using first morning void urine specimen, if possible

2. In those receiving pharmacotherapy

3. Although not optimal, the absence of DHA crystals on urine microscopy can be considered indicative of adequate treatment. A highly significant correlation between 24-hour urinary DHA excretion and DHA crystalluria has been observed .

4. See for information about the UPLC-MS/MS assay for therapeutic monitoring .

5. To evaluate for new, asymptomatic kidney stones

Source: GeneReviews — "Adenine Phosphoribosyltransferase Deficiency"