An Acidic Clue to a Systemic Mystery: Distal Renal Tubular Acidosis Unveils Hereditary Transthyretin Amyloidosis in a Patient with Asperger Syndrome

Introduction: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant condition that typically affects peripheral and autonomic nervous systems, heart, kidneys, and eyes. We present a unique case of distal renal tubular acidosis (dRTA) with nephrocalcinosis and nephrolithiasis leading to the diagnosis of hATTR in a patient with Asperger’s syndrome Case Description: A 32-year-old male with a history of Asperger’s syndrome was referred to clinic due to elevated serum creatinine and metabolic acidosis while undergoing evaluation for thrombocytopenia. Laboratory evaluation showed creatinine of 1.5 mg/dL, CO2 11 mmol/L with anion gap of 10. Electrolytes were normal except for mild hypophosphatemia. Urine analysis was unremarkable except for trace protein and blood and a PH of 8 concerning for the inability to acidify the urine. Urine anion gap was elevated at 42 and 52 repeated on two occasions. Renal ultrasound showed bilateral echogenic medullary pyramids consistent with medullary nephrocalcinosis and non-obstructive bilateral nephrolithiasis. 24-hour urine collection showed hypocitraturia (<50 mg). Altogether, laboratory and imaging findings were pointing toward dRTA with nephrocalcinosis. Serology workup was remarkable for positive ANA and dsDNA antibodies; however, the patient had no systemic manifestations of lupus. Genetic testing revealed a pathogenic heterozygous TTR gene mutation diagnostic for hATTR. Further evaluation showed no cardiac involvement by amyloidosis. Kidney biopsy was pursued and showed acute tubular injury (ATI) with calcium phosphate deposition, Congo red staining was negative, without any evidence of amyloid deposits or lupus nephritis. Despite the use of sodium bicarbonate, serum CO2 remained low at 15 mmol/L. However, after the addition of potassium citrate and lemon juice, CO2 improved and stabilized around 19-20 mmol/L Discussion: This case underscores the diagnostic complexity of renal manifestations in hereditary systemic disorders. The evaluation for distal renal tubular acidosis led to the unexpected diagnosis of hereditary transthyretin amyloidosis (hATTR), highlighting the critical role of genetic testing in broadening the differential diagnosis and uncovering underlying systemic conditions.