In the early 1970s the concept of sudden infant death syndrome (SIDS) was introduced in an attempt to categorize death among infants who die suddenly and unexpectedly and in whom post-mortem investigation fails to provide a credible diagnosis. SIDS today is the largest single cause of death industrialized nations, representing 25 percent of all deaths in the first year of life.
Prior to 1996, only a small number of infant and child deaths were investigated for a "metabolic disorder." This was due to (l) poor access to postmortem screening for inborn errors of the metabolism; (2) the high cost of such testing services from highly specialized laboratories; and (3) limited awareness of new technologies, including the Tandem Mass Spectrometry (MS/MS) for diagnosing underlying metabolic disturbances and disorders.
Since then, advances in technology have facilitated routine postmortem screening for metabolic disorders that may be the underlying cause of death in some infants and children, rather than SIDS. Among the newer technologies is one that screens for metabolic disorders. Using CDC data, the model predicts that 465 infants are likely to be born each year with a metabolic disorder that is detectable by MS/MS. Of the 465 infants with the disorder, 155 are expected to die. Other technology has estimated that the percent of SIDS deaths should be reduced by five percent, as MS/MS has detected that five percent of infant deaths are due to defects within the metabolic system.
A newly published study may not be able to alleviate a parent's grief over a child taken by SIDS, but its findings may help some parents obtain a truer understanding of the cause of an infant's death. A five year review and examination of 7,058 cases of SIDS has been conducted by Donald H. Chace, James C. DiPerna, Brenda L. Mitchell, Bethany Sgroi, Lindsay F. Hofman and Edwin W. Naylor, all from Neo Gen Screening, Inc., Bridgeville, PA. Their findings are contained in the article, "Electrospray Tandem Mass Spectrometry for Analysis of Acylcarnitines in Dried Postmortem Blood Specimens Collected at Autopsy from Infants with Unexplained Cause of Death," published in the peer-reviewed journal Clinical Chemistry. Clinical Chemistry is the flagship publication of the American Association for Clinical Chemistry (AACC).
The study consisted of postmortem blood and bile specimens collected as dried spots on filter paper from 7,058 cases of SIDS collected from all 50 US states and from most Canadian provinces, as well as a few specimens from other countries. Patients were of all races and primarily infants under one year of age. The number of males and females was roughly equal. More than one half of the specimens were from patients with deaths of unknown cause. The trend of samples from the first 1,000 screening specimens compared with the later specimens showed an increasing number of infants who died of any cause, including SIDS.
Each of the samples underwent biochemical screening of numerous metabolic disorders. The screening consisted of acylcarnitine and amino acid profiles were obtained by mass spectometry. Specialized interpretation was used to evaluate profiles for disorders of fatty acid, organic acid, and amino acid metabolism. The analyses of postmortem blood specimens were compared with the analyses of bile specimens, newborn blood specimens, and specimens obtained from older infants at risk for metabolic disorders.
Using the MS/MS-based technology, the researchers discovered that:
- More than 60 (66) specimens suggested diagnoses of metabolic disorders.
- The most frequently detected disorders were: medium-chain and very-long-chain acyl-CoA dehydrogenase deficiencies (23 and 9 cases, respectively), glutaric acidemia type I and II deficiencies (three and eight cases, respectively), carnitine palmitoyl transferase type II/translocase deficiencies (six cases), severe carnitine deficiency (four cases), isovaleric acidemia/2-methylbutyryl-CoA dehydrogenase deficiencies (four cases), and long-chain hydroxyacyl-CoA dehydrogenase/trifunctional protein deficiencies (four cases).
MS/MS-based methodology provides a metabolic screening panel that will enable Medical Examiners to conduct routine screening of infant and child deaths. The benefits are profound.
In utilizing such services, Medical Examiners could advise parents to have infant siblings tested for possible metabolic disorders. Additionally, such screening could be an important component of genetic counseling and family planning for parents. Postmortem metabolic screening also provides a public health service because the number of deaths attributable to inborn errors of metabolism may begin to be assessed. High-volume postmortem screening and the data presented here will begin to demonstrate the importance of even more extensive testing procedures to determine the cause of infant and child death. These data may be developed to find profiles that require additional sophisticated testing, such as enzyme analysis, metabolic studies of skin fibroblasts, and molecular analysis of known mutations.
The importance of developing a routine post-mortem metabolic screen to investigate premature or unexplained death in infants and children cannot be overstated. While toxicology screens are routinely used to eliminate accidental or deliberate poisoning or drug overdoes, the authors urge that MS/MS-based methodology to provide a metabolic screening panel should become equally as routine among medical examiners.