autosomal recessive proximal renal tubular acidosis

Autosomal recessive proximal renal tubular acidosis (AR pRTA) is a multisystem condition that primarily affects how the kidneys handle bicarbonate, an essential buffer that keeps the body’s acid–base balance stable. Variants in the SLC4A4 gene disrupt a transporter protein in the kidney’s proximal tubules, leading to excessive loss of bicarbonate in the urine and systemic metabolic acidosis. Although the kidney problem is central, the disorder also involves the eyes and the nervous system, highlighting that it is more than a kidney disease alone. Precise prevalence figures are not available, but published reports describe only a small number of affected families worldwide, so it is believed to be very rare. Severity and symptoms vary widely between individuals, even among siblings who share the same genetic change.

Most children come to medical attention in infancy or early childhood with poor growth, vomiting, or rapid breathing caused by metabolic acidosis. Laboratory testing shows low blood bicarbonate and potassium levels, along with bicarbonate wasting in the urine that confirms a proximal renal tubular defect. Over time, chronic acidosis and electrolyte imbalance contribute to growth delay and short stature. The condition affects several organ systems. Neurological features include intellectual disability and occasionally cerebral calcifications visible on brain imaging. These cognitive challenges can impact learning and daily living skills, and early developmental support is recommended. Ocular manifestations are prominent: band keratopathy, cataracts, and glaucoma can all develop and threaten vision if not recognized early. In addition, hyperamylasemia, a biochemical finding related to the pancreas, is consistently reported, although it rarely causes symptoms by itself. Not all individuals experience all features, and the type or severity of kidney, eye, or neurological problems can differ greatly, underscoring the variable expressivity of AR pRTA.

AR pRTA results from changes in both copies of the SLC4A4 gene. This gene encodes a sodium bicarbonate cotransporter that is highly active in the kidney’s proximal tubule. When the transporter is absent or malfunctioning, bicarbonate that should be reclaimed from the filtrate is lost in the urine, leading to systemic acidosis and the downstream complications described above. The condition follows an autosomal recessive inheritance pattern, meaning an individual must inherit one pathogenic SLC4A4 variant from each parent to be affected. Parents who each carry a single variant typically have no symptoms but have a 25 percent chance with each pregnancy of having an affected child. Because this disorder is very rare, it is more likely to occur in families in which parents share a common ancestor, which increases the chance that both carry the same rare genetic change. Genetic counseling can help families understand carrier testing options, discuss reproductive planning, and provide individualized recurrence risk information.

Currently, management focuses on correcting the acid–base imbalance and preventing complications. Oral bicarbonate or citrate supplementation is commonly used to neutralize excess acid and support normal growth. Potassium replacement may also be required to address hypokalemia. Eye problems such as cataracts or glaucoma are treated according to standard ophthalmologic practice, which can include medication or surgery. Neurological and cognitive challenges benefit from early intervention services, individualized education plans, and therapies such as speech or occupational therapy. Because the condition affects multiple organ systems, care is best coordinated by a multidisciplinary team that may include nephrologists, ophthalmologists, neurologists, endocrinologists, and developmental specialists. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Monitoring typically includes periodic assessment of growth, blood chemistries, and eye health, as well as developmental evaluations. Families are encouraged to maintain close communication with their healthcare providers to adjust treatment as needs evolve. Genetic counseling should be offered to affected individuals and carrier relatives when making family planning decisions.

With prompt diagnosis and diligent metabolic management, many children experience improved growth and avoid severe metabolic crises. Vision outcomes depend on early detection and treatment of ocular complications, while cognitive challenges may persist but can be mitigated through supportive educational services. Outcomes described in medical literature continue to evolve as standards of care improve. Individual experiences with this condition differ significantly, and long-term outlook depends on factors such as the severity of acidosis, effectiveness of treatment adherence, and timely management of eye and neurological issues. Families often find it helpful to connect with specialists familiar with renal tubular disorders and to engage genetic counselors who can explain inheritance and available support resources.

Clinical trials are underway exploring new treatment approaches for proximal renal tubular acidosis. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.