In a patient with dizziness, a short PR interval on ECG, low alkaline phosphatase, low alanine aminotransferase, low aspartate aminotransferase, low anion gap, and high red‑cell distribution width, what is the most likely diagnosis and recommended management?

Wolff-Parkinson-White (WPW) Syndrome with Possible Fabry Disease

This constellation of findings—dizziness, short PR interval, low alkaline phosphatase, low transaminases, low anion gap, and high RDW—strongly suggests Wolff-Parkinson-White syndrome with concurrent Fabry disease, a rare X-linked lysosomal storage disorder that characteristically presents with short PR interval, left ventricular hypertrophy, and multisystem involvement. 1, 2

Immediate Diagnostic Priorities

Obtain a 12-lead ECG immediately to assess for delta waves and QRS widening. The presence of a delta wave (slurred QRS upstroke) with QRS >120 ms confirms WPW pattern, while isolated short PR without delta wave may represent either a benign variant or Lown-Ganong-Levine syndrome. 1, 2, 3

ECG Interpretation Algorithm

• If delta wave present: WPW syndrome confirmed—proceed to urgent risk stratification regardless of symptoms, as sudden cardiac death can be the first presentation in approximately 50% of cases. 4, 3

• If no delta wave: Consider Lown-Ganong-Levine syndrome or benign variant, but maintain high suspicion for intermittent pre-excitation which may not be visible on every ECG. 1, 5

Critical Laboratory Pattern Recognition

The combination of low alkaline phosphatase, low ALT, low AST, and low anion gap is highly unusual and warrants specific consideration:

• Fabry disease must be excluded in any patient presenting with short PR interval and unexplained multisystem laboratory abnormalities, particularly with dizziness suggesting cardiac involvement. 2

• High RDW may reflect chronic hemolysis or nutritional deficiencies, but in the context of short PR interval and low liver enzymes, consider glycogen storage diseases including Fabry disease (incidence 1 in 40,000-60,000 males). 2

• Low anion gap (<6 mEq/L) combined with these findings raises concern for hypoalbuminemia or paraproteinemia, which can occur in advanced Fabry disease with renal involvement. 2

Mandatory Cardiovascular Workup

All patients with confirmed WPW pattern require comprehensive evaluation before any reassurance can be given, even if asymptomatic. 1, 4

Essential Testing Sequence

• Transthoracic echocardiography: Rule out hypertrophic cardiomyopathy, Ebstein anomaly, left ventricular hypertrophy (characteristic of Fabry disease), and PRKAG2-related familial WPW. 1, 2

• Exercise stress testing: Abrupt loss of pre-excitation during exercise indicates low risk and long accessory pathway refractory period; intermittent pre-excitation suggests benign course. 1, 4

• 24-hour Holter monitoring: Document paroxysmal tachyarrhythmias and assess for intermittent pre-excitation patterns associated with lower risk. 1

• Electrophysiology study: Mandatory for symptomatic patients or those with high-risk features to assess accessory pathway refractory period and inducibility of AV re-entrant tachycardia. 1, 4

Risk Stratification for Sudden Cardiac Death

High-risk features requiring urgent intervention include: 4

• Shortest pre-excited RR interval <250 ms during atrial fibrillation
• History of syncope or near-syncope (dizziness in this patient warrants urgent evaluation)
• Multiple accessory pathways
• Ebstein anomaly on echocardiography
• Accessory pathway refractory period <240 ms

Low-risk indicators: 1, 4

• Intermittent loss of pre-excitation on ambulatory monitoring
• Abrupt disappearance of pre-excitation during exercise testing

Fabry Disease Screening Protocol

Given the unique laboratory constellation, alpha-galactosidase A enzyme activity testing is indicated, particularly if echocardiography demonstrates left ventricular hypertrophy. 2

• Fabry disease characteristically presents with short PR interval, sinus bradycardia, and LVH
• Multisystem symptoms may include angiokeratomas, acroparesthesias, corneal verticillata, and progressive renal dysfunction
• Early diagnosis is critical as enzyme replacement therapy can prevent progression

Definitive Management Algorithm

For Confirmed WPW with Delta Wave:

Catheter ablation is first-line definitive treatment with 95-98.5% success rates and only 0.1-0.9% major complication rates. 4

Mandatory ablation indications: 4

• Symptomatic tachyarrhythmias (dizziness qualifies)
• History of syncope
• Any high-risk features identified on electrophysiology study
• Documented atrial fibrillation with pre-excitation

For Isolated Short PR Without Delta Wave:

• If asymptomatic with normal echocardiogram and no high-risk findings on exercise testing or Holter monitoring, likely benign variant requiring only periodic surveillance. 1

• If symptomatic (dizziness), beta-blockers can control supraventricular tachycardia episodes pending further evaluation. 2

Critical Medication Contraindications

Never administer AV nodal blocking agents (digoxin, diltiazem, verapamil, beta-blockers) in pre-excited atrial fibrillation, as these accelerate conduction through the accessory pathway and can precipitate ventricular fibrillation. 4, 6

• For hemodynamically unstable wide-complex tachycardia: immediate synchronized DC cardioversion 4

• For stable pre-excited atrial fibrillation: IV procainamide is first-line 4, 6

• For stable narrow-complex regular tachycardia: vagal maneuvers and IV adenosine are appropriate 4

Common Pitfalls to Avoid

• Do not dismiss WPW pattern as benign even in asymptomatic patients—sudden death can occur without warning, and cardiac arrest is the first manifestation in approximately 50% of WPW patients who experience it. 4

• Do not attribute short PR with LVH to hypertension or athletic heart without excluding Fabry disease, particularly with unexplained low liver enzymes. 2

• Do not rely on a single normal ECG to exclude WPW—intermittent pre-excitation may not be visible on every tracing. 5

• Do not use verapamil in wide-complex or irregular tachycardia without confirming the rhythm is not pre-excited atrial fibrillation. 6

Immediate Next Steps for This Patient

1. Obtain 12-lead ECG now to assess for delta waves
2. Order transthoracic echocardiography urgently to evaluate for structural heart disease and LVH
3. Send alpha-galactosidase A enzyme level given the unusual laboratory pattern
4. Refer to cardiology within 48 hours for risk stratification and consideration of electrophysiology study
5. Advise patient to avoid competitive sports until risk stratification is complete 2