renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss

Renal tubular acidosis, distal, 2, with progressive sensorineural hearing loss is a genetic condition that affects both kidney function and hearing. The kidneys are unable to properly acidify urine, leading to a build-up of acid in the blood, while the inner ear gradually loses the ability to transmit sound, causing hearing loss that worsens over time. Pathogenic variants in the ATP6V1B1 gene, which encodes a component of the vacuolar ATPase proton pump, underlie the disorder. Symptoms usually begin in infancy or early childhood, but hearing loss may not be apparent until later. Precise prevalence figures are not well established, reflecting the rarity of the condition.

The clinical picture is dominated by problems of acid–base balance and progressive hearing impairment. Early signs often include excessive thirst, frequent urination, or poor growth related to chronic metabolic acidosis. As children grow older, many develop sensorineural hearing loss that typically worsens over time and can progress to severe or profound deafness. Some individuals experience episodes of muscle weakness or kidney stones related to long-standing acidosis. Not all individuals experience all features, and severity varies considerably.

The condition is caused by pathogenic variants in the ATP6V1B1 gene. This gene provides instructions for making a subunit of the vacuolar ATPase proton pump, a protein complex that helps move hydrogen ions across cell membranes. In the kidneys, the pump is essential for acidifying urine in the distal tubules, and in the inner ear it helps maintain the delicate fluid balance needed for hearing. Loss of pump function leads to systemic acidosis and progressive damage to the cochlea. The disorder follows an autosomal recessive inheritance pattern, meaning an individual must inherit two non-working copies of ATP6V1B1, one from each parent, to be affected. Parents who each carry one altered copy (carriers) are typically healthy but have a 25 percent chance with each pregnancy of having an affected child. Carrier testing and genetic counseling are recommended for family members.

Currently, management focuses on supportive care and symptom management. Correction of metabolic acidosis with oral alkali therapy (such as bicarbonate or citrate preparations) is a cornerstone of care and can improve growth and bone health. Hearing support may include regular audiologic monitoring, hearing aids, or cochlear implantation when indicated. Care is typically coordinated by a multidisciplinary team that may include nephrologists, audiologists, otolaryngologists, dietitians, and genetic counselors. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation, and relatives should be offered carrier testing and genetic counseling.

With prompt correction of acidosis and ongoing renal and audiologic care, many individuals achieve normal growth and avoid serious kidney complications. Hearing loss is progressive, but early identification and appropriate use of auditory technologies can support language development and quality of life. Long-term outcomes vary, especially if treatment is delayed, but modern management has substantially improved outlook for affected individuals.