Cardiac Mechanisms and Inborn Errors of Metabolism

Evaluating Cardiac Mechanisms

Evaluation of Long QT Syndrome and Other Cardiogenetic Arrythmias in the Living First Degree Relatives (Parents and Siblings of the person who has died) should speak to their Primary Physician to obtain a referral to a Cardiologist to perform:

  1. A VERY careful and detailed medical history of the decedent with review of the autopsy report and sometimes the autopsy tissue itself
  2. A VERY careful and thorough review of the family history with pedigree analysis on both sides searching for the "needles in a haystack"

If anything is suggestive of a possible cardiac mechanism: screen siblings and parents with an electrocardiogram (EKG or ECG) and an echocardiogram (ECHO). Additional testing may be indicated based on the clinical and family history, the deceased child's death investigation findings and the results of the preliminary tests of the EKG and ECHOs.
 
Long QT Syndrome (LQTS) is a disorder of the electrical system of the lower chambers of the heart (ventricles) and just one type of inheritable disorder.

Some Cardiologists have special training to evaluate genetic cardiac disorders. If you are having trouble locating a specialist, please contact the SUDC Foundation at 800-620-SUDC.

Post Mortem Evaluation of Long QT Syndrome (LQTS) Today: Options through Research and Commercial Testing
Today, two options exist as set forth below to diagnose Long QT Syndrome in a person that has died. Both have their pros and cons. Discuss these options with your Doctor so you can come to the best decision for your particular family.

  1. Commercial, clinical LQTS genetic testing via FAMILION (www.familion.com), It tests for 5 of the known Long QT syndrome genes. Length of time from testing to results: about 4 - 6 weeks, Participation requires blood in EDTA, or autopsy tissue specimens. The postmortem screening panel of channelopathies costs about $2500. *FYI: Postmortem genetic testing is so far unlikely to be paid for by insurance.
  2. Research genetic testing in Mayo Clinic's Sudden Death Genomics Laboratory – IRB-approved, free, and consent of appropriate next of kin is required. Here, the focus is on discovery and the research subject’s specific “service” is a hoped for result with successful elucidation of novel causes for sudden unexplained death. Length of time from testing to results: SLOW! Usually more than one year. In general, contact with the medical examiners and families only occur in the event that the research testing identifies a probable genetic cause. Participation: Requires DNA from deceased that is adequate for testing (i.e., frozen tissue that is DNA rich, blood in EDTA, blood spot cards). In general, formalin fixed tissue and paraffin-embedded tissue will NOT permit a successful molecular autopsy. Contact: Long QT Syndrome Clinic # 507-284-0101.

References

  • Ackerman et al. HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for Channelopathies and Cardiomyopathies. Heart Rhythm, Vol 8, No 8, August 2011
  • Ackerman MJ, Tester DJ, Driscoll, DJ. Molecular autopsy of sudden unexplained death in the young. The American Journal of Forensic Medicine and Pathology. 2001; 22(2): 105-111.
  • Ackerman MJ, Khosiseth A, Tester DJ, Hejlik J, Shen WK, Porter CJ. Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. Mayo Clinic Proceedings. 2002;77:413-421.
  • Tester DJ, Spoon DS, Valdivia HH, Makielski JC, Ackerman MJ. Targeted Mutational Analysis of RyR2-Encoded Cardiac Ryanodine Receptor in Sudden Unexplained Death: A Molecular Autopsy of 49 Medical Examiner/Coroner Cases. Mayo Clinical Proceedings, 2004, 79 (11): 1380-1384 www.mayo.edu/proceedings

Evaluating Inborn Errors of Metabolism

Mayo Medical Labs Communique-The Metabolic Autopsy: Portmortem Screening in Cases of Sudden Unexpected Death.

2009 Mayo Medical Labs Metabolic Autopsy Protocol (used in NJ and other States)

References

  • Bennett MJ, Rinaldo P. The Metabolic Autopsy comes of Age. Clinical Chemistry 47; 1145-6, 2001
  • Tortorelli S, Hahn SH, Cowan TM, Brewster TG, Rinaldo P, Matern D. The urinary excretion of glutarylcarnitine is an informative tool in biochemical diagnosis of glutaric acidemia type 1. Molecular Genetics and Metabolism 84:137-143, 2005