Diagnosis: Proximal (Type 2) Renal Tubular Acidosis
The most likely diagnosis is proximal renal tubular acidosis (Type 2 RTA), which presents with recurrent hypokalemic periodic paralysis, normal anion gap metabolic acidosis, and features of Fanconi syndrome. 1, 2, 3
Clinical Reasoning Algorithm
Step 1: Identify the Acid-Base Disorder
Normal anion gap metabolic acidosis is confirmed by pH 7.29 (acidemic), bicarbonate 11.6 mmol/L (severely low), and calculated anion gap of approximately 10-12 mEq/L (Na 146 - [Cl + HCO3 11.6] = normal range). 4, 3, 5
The low bicarbonate (<22 mmol/L) with acidemia (pH <7.35) definitively establishes metabolic acidosis as the primary disorder. 4
The low PaCO2 (27 mmHg) represents appropriate respiratory compensation for the metabolic acidosis, not a primary respiratory alkalosis—the expected PaCO2 for a bicarbonate of 11.6 mmol/L is approximately 24-28 mmHg using Winter's formula. 4
Step 2: Narrow the Differential for Normal Anion Gap Acidosis
Proximal RTA (Type 2) causes normal anion gap acidosis through impaired bicarbonate reabsorption in the proximal tubule, typically presenting as part of Fanconi syndrome with multiple proximal tubular transport defects. 1, 2, 6, 7
Distal RTA (Type 1) also causes normal anion gap acidosis but through impaired distal acid excretion; however, the very low BUN/creatinine ratio (0.8) and recurrent paralysis pattern favor proximal RTA with Fanconi syndrome features. 3, 5, 7
Alcoholic ketoacidosis is excluded because it produces a high anion gap metabolic acidosis from accumulation of beta-hydroxybutyrate and acetoacetate, not a normal anion gap. 4
Ethylene glycol intoxication is excluded because it causes high anion gap metabolic acidosis from glycolic and oxalic acid accumulation, plus this patient has no history of ingestion and presents with recurrent episodes. 4
Stage V CKD is excluded because the BUN/creatinine ratio of 0.8 is abnormally low (normal 10-20:1), suggesting intact renal function with possible proximal tubular wasting rather than advanced kidney failure. 4
Step 3: Confirm Proximal RTA Features
Severe hypokalemia (K 2.6 mmol/L) with flaccid paralysis is characteristic of Type 2 RTA, where bicarbonate wasting leads to increased distal sodium delivery, stimulating aldosterone-mediated potassium secretion and causing profound hypokalemia that can produce periodic paralysis. 1, 3, 7
Recurrent episodes of paralysis ("similar history few months back") strongly suggest an underlying chronic tubular disorder rather than acute intoxication or end-stage kidney disease. 1, 3
ECG T-wave flattening is a classic manifestation of severe hypokalemia (K <3.0 mmol/L), which can also cause U waves, ST depression, and life-threatening arrhythmias if untreated. 1, 3
The very low BUN/creatinine ratio (0.8) suggests proximal tubular dysfunction with impaired urea reabsorption as part of generalized Fanconi syndrome, rather than prerenal azotemia or intrinsic renal failure. 2
Hypernatremia (Na 146 mmol/L) may reflect volume contraction from urinary losses in Fanconi syndrome or inadequate free water intake during paralytic episodes. 2
Step 4: Exclude Alternative Diagnoses
Distal RTA (Type 1) is less likely because it typically presents with less severe hypokalemia at baseline, nephrocalcinosis, and bone disease rather than the acute severe hypokalemic paralysis pattern seen here. 3, 5, 7
Type 4 RTA is excluded because it causes hyperkalemia (not hypokalemia) due to aldosterone deficiency or resistance. 3, 5, 6, 7
Diarrheal losses would cause normal anion gap acidosis but would not explain the recurrent paralysis pattern, lower motor neuron findings, or the very low BUN/creatinine ratio suggesting tubular dysfunction. 4
Key Diagnostic Features Supporting Proximal RTA
Normal anion gap metabolic acidosis (pH 7.29, HCO3 11.6 mmol/L, anion gap ~10-12 mEq/L) indicates either GI bicarbonate loss or renal tubular dysfunction. 4, 3, 5
Severe hypokalemia (2.6 mmol/L) with recurrent flaccid paralysis is pathognomonic for hypokalemic periodic paralysis secondary to chronic RTA with massive urinary potassium wasting. 1, 3
Low BUN/creatinine ratio (0.8) suggests proximal tubular dysfunction with impaired urea reabsorption, a feature of Fanconi syndrome that accompanies Type 2 RTA. 2
Young age (21 years) with recurrent episodes favors an inherited tubular disorder rather than acquired causes like multiple myeloma or drug toxicity. 2, 3, 8
Critical Next Steps
Measure urine pH during acidemia: In proximal RTA, urine pH is typically <5.5 when plasma bicarbonate is low (<15 mmol/L) because the distal tubule can still acidify urine once the reabsorptive threshold is exceeded. 5, 6, 7
Calculate fractional excretion of bicarbonate (FEHCO3) after bicarbonate loading: FEHCO3 >15% at normal plasma bicarbonate confirms proximal RTA. 5, 6, 7
Screen for Fanconi syndrome features: Check for glucosuria (with normal serum glucose), aminoaciduria, phosphaturia, and uricosuria to confirm generalized proximal tubular dysfunction. 9, 2
Genetic testing for mutations in SLC4A4 (encoding NBC-1 transporter) should be considered in young patients with isolated proximal RTA, especially if ocular abnormalities are present. 8
Common Pitfalls to Avoid
Do not diagnose diabetic ketoacidosis based solely on acidosis and low bicarbonate—DKA produces high anion gap acidosis with hyperglycemia >250 mg/dL, not normal anion gap acidosis. 4
Do not attribute the acidosis to respiratory compensation—the low PaCO2 (27 mmHg) is appropriate respiratory compensation for severe metabolic acidosis, not a primary disorder. 4
Do not overlook the urgency of severe hypokalemia—potassium <2.6 mmol/L can cause fatal cardiac arrhythmias and requires immediate aggressive replacement before addressing the acidosis. 1, 3
Do not give bicarbonate alone without potassium—correcting acidosis will drive potassium intracellularly and can precipitate life-threatening hypokalemia and cardiac arrest. 4, 1