Phenotypic-Genotypic Discordance in Renal Tubular Acidosis with Hypokalemic Rhabdomyolysis and a TRAPPC2 Variant: A Case Report

Abstract Background Renal tubular acidosis (RTA) encompasses disorders of renal acid–base regulation that may cause hypokalemia, metabolic bone disease, and growth retardation. Distal RTA (dRTA) is characterized by hyperchloremic, normal-anion-gap metabolic acidosis with urine pH > 5.5. Distinguishing proximal from distal RTA is challenging when clinical, biochemical, and genetic findings are discordant. Hypokalemia-induced rhabdomyolysis is uncommon, and the coexistence of RTA with spondyloepiphyseal dysplasia tarda (SEDT) remains poorly characterized. Case presentation A normotensive man in his early twenties presented with an eight-year history of recurrent hypokalemic flaccid quadriparesis, myalgia, polyuria, short stature, severe back pain, and impaired mobility. During an acute episode, serum potassium was 1.7 mmol/L and creatine phosphokinase (CPK) was 17,384 U/L, suggesting hypokalemia-induced rhabdomyolysis. Subsequent investigations demonstrated hyperchloremic normal-anion-gap metabolic acidosis, urine pH > 5.5, a positive urinary anion gap, hypercalciuria, hypophosphatemia, hypouricemia, and bilateral medullary nephrocalcinosis, supporting a distal RTA phenotype. Imaging revealed osteomalacia, pseudofractures, kyphosis, and bilateral sacroiliitis; dual-energy X-ray absorptiometry (DEXA) scan showed severe osteoporosis. Back pain and sacroiliitis initially suggested seronegative spondyloarthropathy (SSpA), but normal inflammatory markers, negative HLA-B27, and lack of response to immunomodulatory therapy prompted diagnostic reconsideration. Whole-exome sequencing identified heterozygous GATM c.181C > G (p.Pro61Ala) and hemizygous TRAPPC2 c.176T > C (p.Met59Thr) variants of uncertain significance. The GATM variant is associated with Fanconi renotubular syndrome type 1, despite the predominantly distal RTA phenotype. Maternal Sanger sequencing confirmed heterozygosity for the TRAPPC2 variant. Disproportionate short stature and skeletal abnormalities raised suspicion of coexisting X-linked SEDT. Treatment with potassium citrate, sodium bicarbonate, calcium, cholecalciferol, and teriparatide improved symptoms and bone mineral density at one year, although mild metabolic acidosis persisted. Conclusions This case highlights the diagnostic complexity of discordant renal tubular phenotypes and genetic findings. Hypokalemic rhabdomyolysis and metabolic bone disease may provide important diagnostic clues. Sacroiliitis may mimic inflammatory spondyloarthritis, emphasizing the need to consider metabolic and skeletal disorders. Further segregation and functional studies are needed to clarify the identified variants and investigate a possible association between RTA and SEDT.