Clinical Guidance

CLCN5. Genotype-phenotype correlations have yet to be established. OCRL. It has been suggested that pathogenic variants in OCRL are associated with a phenotypic spectrum ranging from Lowe syndrome at the severe end to Dent disease 2 at the mild end. Note: Although the renal tubulopathy in Lowe syndrome (which is mainly characterized by altered protein reabsorption) and Dent disease is similar, it is generally milder in Dent disease. Of note, this milder Dent disease phenotype could not be attributed to lesser protein expression or enzyme activity.

Source: GeneReviews — "Dent Disease"

Diagnostic Criteria

Suggestive Findings

Dent disease should be suspected in an individual with the three criteria below in the absence of other known causes of proximal tubule dysfunction . Note: A possible diagnosis of Dent disease is considered if LMW proteinuria and at least one other criterion are present.

Source: GeneReviews — "Dent Disease"

Differential Diagnosis

The differential diagnosis of Dent disease includes other causes of proximal tubular dysfunction. Renal Fanconi syndrome. The presence of more generalized proximal tubular dysfunction (glucosuria, amino aciduria, renal tubular acidosis) would suggest the possibility of a renal Fanconi syndrome. Causes of renal Fanconi syndromes can be hereditary (e.g., Wilson disease, glycogen storage disease) or acquired (e.g., exposure to heavy metal, toluene, or cisplatin). Glomerular disease. Some individuals with Dent disease 1 with more severe proteinuria were found to have focal segmental glomerulosclerosis (FSGS) or global sclerosis on kidney biopsy . Most cases of FSGS are idiopathic, but FSGS can be seen in association with obesity or progressive chronic kidney disease of any cause.

Source: GeneReviews — "Dent Disease"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with Dent disease, the following evaluations are recommended if they have not already been completed:

• Assessment of renal function (measured or estimated GFR; urine protein excretion)

• Assessment for nephrocalcinosis and kidney stones by imaging studies, typically low-dose noncontrast CT scan or ultrasound

For those with evidence of renal stones or nephrocalcinosis, urine studies for kidney stone risk factors (including calcium and citrate excretion)

• Assessment of risk for bone disease (serum calcium, phosphorus, and alkaline phosphatase)

Note: Elevated alkaline phosphatase has been reported in all individuals with clinical rickets . For those with evidence of bone disease and/or growth delay, more complete assessment of bone health (i.e., serum vitamin D concentration and PTH level; x-ray of long bones for evidence of osteomalacia)

• In children, evaluation of stature using standard growth charts. If short stature is present, evaluation by an endocrinologist for the possibility of growth hormone therapy can be considered.

• Evaluation for intellectual disability

• Careful eye exam for cataracts, especially if there is any concern for visual impairment

• Consultation with a clinical geneticist and/or genetic counselor

• Although it is not necessary to specifically screen for the possibility, elevated serum muscle enzyme levels are often seen in patients with Dent disease.

Source: GeneReviews — "Dent Disease"

Clinical Guidance

Exposure to potential renal toxins (nonsteroidal anti-inflammatory drugs, aminoglycoside antibiotics, and intravenous contrast agents) should be avoided, especially if renal function is below 45 mL/min/1.73 m2 (CKD stage 3B).

Source: GeneReviews — "Dent Disease"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Dent Disease"

Surveillance Guidelines

Renal function measured as glomerular filtration rate (GFR) should be monitored at least annually together with the parameters used to stage chronic kidney disease (i.e., blood pressure, hematocrit/hemoglobin, urinary calcium excretion, and serum calcium and phosphorus concentrations). More frequent visits and monitoring for complications of chronic kidney disease (i.e., hypertension, anemia, and secondary hyperparathyroidism) as well as consideration of intensified treatment of cardiovascular risk factors may be indicated if GFR falls below 45 mL/min/1.73 m2 (CKD Stage 3B).

Source: GeneReviews — "Dent Disease"