Introduction:
Primary distal renal tubular acidosis (dRTA) is characterized by an impaired ability of the distal tubule to excrete acid due to genetic defect (involved genes ATP6V0A4, ATP6V1B1, SLC4A1, FOXI1, or WDR72), which leads to persistent hyperchloremic metabolic acidosis and other renal and extrarenal complications. The aim of the study was to evaluate clinical and molecular characteristics of dRTA in Russian children.
Methods:
We conducted retrospective longitudinal study of 12 children (6M/6F) with dRTA associated with variants in the following genes: SLC4A1 (n=5), АТР6V1B1 (n=5), ATP6V0A4 (n=2). The median age of onset of first symptoms of the disease was 12.0 (2.0; 19.5) months. The median time period from the onset of disease to clinical diagnosis of dRTA was 9.0 (2.0; 28.0) months. The median age of patients at the first follow up was 33.7 (10.1; 70.2) months.
Results:
The first symptoms of the dRTA appeared significantly earlier in children with dRTA due to variants in the АТР6V1B1/ATP6V0A4 genes, than in patients with variants in the SLC4A1 gene: 2.0 (2.0; 12.0) vs 21.0 (18.0; 24.0) months (p=0.0028). The first symptoms of dRTA were: vomiting and failure to thrive in 4/5 (80%) and 2/2 (100%) of patients with ATP6V1B1- and ATP6V0A4-associated dRTA, respectively; rickets and growth retardation in 3/5 (60%) of cases with SLC4A1-associated dRTA. Metabolic acidosis in 2/5 (40%) of children with SLC4A1-associated dRTA and medullary nephrocalcinosis in 1/5 (20%) of patients with ATP6V1B1-associated dRTA were detected by routine examination.
Among patients with dRTA metabolic acidosis, decreased serum uric acid (UA) level due to loss with urine (increased FEUr), increased low-molecular-weight proteinuria (LMWP) and nephrocalcinosis at the first follow-up were revealed in 12/12 (100%) of cases, hypokalemia in 11/12 (91.7%), rickets in 8/12 (66.7%), hypercalciuria in 7/12 (58.3%), increased serum ALP, decreased TmP/GFR level, sensorineural hearing loss in 6/7 (85.7%) of children with АТР6V1B1/ ATP6V0A4- associated dRTA and renal cysts in 6/12 (50%) patients, weight and height SDS Z score <2 were detected in 6/12 (50%) and 3/12 (25%) children, respectively; hypophosphatemia in 4/12 (33.3%), urolithiasis in 3/12 (25%) subjects, none of children had glucosuria.
Conclusions:
The age of onset and the first clinical symptoms of dRTA depend on the type of genetic defect. The most common first clinical symptoms of dRTA are vomiting, slow weight gain, rickets and growth retardation. All children with dRTA presented with features of proximal tubular dysfunction various degrees of severity. The most prevalent features of proximal tubular dysfunction in our study were LMWP, decreased serum UA and phosphaturia.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.