Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.

OCRL mutations, which are a hallmark of Lowe syndrome, have recently been found in patients with isolated renal phenotype (Dent-2 disease). In this report, we describe clinical and laboratory features in five Macedonian children with mutations in the OCRL gene. Children with a clinical diagnosis of Lowe syndrome or Dent disease underwent complete neurological and ophthalmological examination, imaging of the kidney and urinary tract, assessment of renal tubular function, and mutation analysis of the OCRL gene. Two children (18 months and 11 years, respectively) were diagnosed with Lowe syndrome on the basis of congenital cataracts, severe psychomotor retardation, and renal dysfunction. Both children had low molecular weight proteinuria (LMWP) and hypercalciuria, but not Fanconi syndrome. The older one had bilateral nephrolithiasis due to associated hypocitraturia and mild hyperoxaluria. Three children with asymptomatic proteinuria were diagnosed with Dent-2 disease; none had cataracts or neurological deficit. One child showed mild mental retardation. All had LMWP, hypercalciuria, and elevated enzymes (creatine phosphokinase, lactic dehydrogenase). All three children had an abnormal Tc-99m DMSA scan revealing poor visualization of the kidneys with a high radionuclide content in the bladder; none had nephrolithiasis or nephrocalcinosis. In conclusion, children with OCRL mutations may present with very mild phenotype (asymptomatic proteinuria with/without mild mental retardation) or severe classic oculocerebrorenal syndrome of Lowe. Elevated enzymes and abnormal results on the Tc-99m DMSA scan may be useful indicators for Dent-2 disease.

No abstract

No abstract

Children with Dent phenotype who lack CLCN5 mutation should be tested for OCRL1 mutation. OCRL1 mutations may present with mild clinical features and are not necessarily associated with congenital cataracts.