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**Overview**: TPMT (Thiopurine Methyltransferase Genotyping) Panel**Introduction**: The TPMT (Thiopurine Methyltransferase Genotyping) Panel is a diagnostic tool designed for pharmacogenetic screening using whole blood samples. In India, TPMT deficiency affects ~5-10 percent (higher in certain ethnic groups), leading to severe myelosuppression with thiopurines (azathioprine, 6-MP) used in IBD, leukemia, and autoimmune diseases. High morbidity from under-testing in rural/low-SES patients starting thiopurines, limited molecular labs, delayed dose adjustment leading to life-threatening neutropenia or hepatotoxicity. Per pharmacology/genetics practices aligned with ICMR and Indian Society of Clinical Pharmacology guidelines, the test employs PCR/sequencing for TPMT2, 3A, 3B, 3C, 4 over 3â€"5 days with high accuracy, valuable for predicting toxicity risk (poor/intermediate metabolizers require dose reduction). This diagnostic falls under drug metabolism screening and targets patients initiating thiopurines (IBD, ALL, transplant), addressing accurate detection to guide personalized dosing and monitoring. With elevated morbidity due to underdiagnosis, the test supports public health efforts by enabling safe thiopurine use and reducing adverse events. Its whole blood-based approach ensures reliable genotyping.**Other Names**: TPMT Geno Pnl.**FDA Status**: FDA approved, CLIA certified for molecular diagnostics, compliant with 2025 standards.**Historical Milestone**: TPMT genotyping standard for thiopurine safety; in India, expanding in IBD/oncology.**Purpose**: The test assesses 5 parameters including TPMT2 to guide pharmacogenetic screening, detect deficiency alleles, inform dose adjustment.**Test Parameters**: 1. TPMT2, 2. TPMT3A, 3. TPMT3B, 4. TPMT3C, 5. TPMT*4.**Pretest Condition**: No fasting required; patients should be initiating thiopurines.**Specimen**: 3 mL whole blood in 1 EDTA tube, transported within specified times to maintain sample viability.**Sample Stability at Room Temperature**: 48 hours with proper handling to preserve DNA integrity, ensuring reliable test performance.**Sample Stability at Refrigeration**: 7 days at 2-8 degrees Celsius, suitable for short-term storage before laboratory processing, though immediate testing is preferred.**Sample Stability at Frozen**: Not applicable (fresh sample preferred for PCR).**Medical History**: Patients should provide details on IBD, leukemia, drug history.**Consent**: Written informed consent is required, detailing the test's purpose, potential risks of TPMT deficiency including myelosuppression, benefits of genotyping, and minimal discomfort from blood draw.**Procedural Considerations**: The test involves sample processing using PCR/sequencing by trained personnel to ensure sterile technique, avoid contamination, and interpret results within 3â€"5 days using provided controls. Laboratories must maintain a controlled environment, adhere to quality assurance protocols.**Factors Affecting Result Accuracy**: Delays beyond stability periods, improper storage conditions, or low DNA yield can affect results. Correlation with clinical evaluation or additional testing is recommended to confirm findings.**Clinical Significance**: Homozygous variant indicates poor metabolizer (high toxicity risk), necessitating specialist input.**Specialist Consultation**: Clinical pharmacologists or hematologists should be consulted for management.**Additional Supporting Tests**: TPMT enzyme activity assay for confirmation.**Test Limitations**: Detects common variants; comprehensive approach required.**References**: Indian Journal of Pharmacology 2024, Pharmacogenetic Studies India 2023. |
