More on the metabolic autopsy.
We were interested by the paper of Chace et al. (1) and the accompanying editorial (2) on the postmortem diagnosis of organic acid and fatty acid defects by analysis of acyl carnitines in dried-blood-spot specimens and fully support the need for metabolic investigations in this situation.
The group reports 66 presumptive or confirmed diagnoses from a total of 7058 postmortem specimens (0.9%). The major diagnoses were fatty acid oxidation defects, particularly medium-chain acyl CoA dehydrogenase deficiency. In some cases, the diagnosis remained presumptive because confirmatory tests were not available.
We have experience, albeit limited, in the investigation of all cases of sudden unexplained death in infants (SUDI) <2 years of age in the City of Birmingham, United Kingdom. Our protocol includes plasma and bloodspot acyl carnitines and amino acids, urine organic acids, and the collection of a skin biopsy, which is stored frozen pending preliminary results. Over a 2.5-year period, we have investigated 58 cases. Definitive diagnosis was established in three cases (5% total). The diagnoses made were long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (confirmed by mutation analysis), carnitine transporter defect (confirmed by cultured fibroblast fatty acid oxidation), and citrullinemia (confirmed by cultured fibroblast citrulline incorporation). Seven additional cases had acyl carnitine analyses that suggested the possibility of a fatty acid defect (see Table 1). The frozen skin biopsies from these patients were subsequently cultured for fatty acid oxidation studies (3), which were normal.
These findings illustrate the importance of collecting a skin biopsy as well as blood to enable a definitive diagnosis. The biopsy can be frozen at the time of collection and then cultured only if required (4). In the United Kingdom we feel that this is a practical approach for the investigation of all cases of SUDI <2 years of age.
The ability to make a definitive diagnosis is important for genetic counseling and enabling the possibility of prenatal diagnosis; we would like to emphasize that a skin biopsy be routine as part of a protocol for investigation for metabolic disease in SUDI.
(1.) Chace DH, DiPerna JC, Mitchell BL, Sgroi B, Hogman LF, Naylor EW. Electrospray tandem mass spectrometry for analysis of acyl carnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death. Clin Chem 2001;47: 1166-82.
(2.) Bennett MJ, Rinaldo P. The metabolic autopsy comes of age [Editorial]. Clin Chem 2001;47: 1145-6.
(3.) Olpin SE, Manning NJ, Pollitt RJ, Bonham JR, Downing M, Clark S. The use of [9,10-[sup.3]H]myristate, [9,10-[sup.3]H]palmitate and [9,10-[sup.3]H]oleate for the detection and diagnosis of medium and long-chain fatty acid oxidation disorders in intact cultured fibroblasts. Exp Med Biol 1999; 466:321-5.
(4.) Gray RGF, Ryan D, Green A. The cryopreservation of skin biopsies--a technique for reducing workload in a cell culture laboratory. Ann Clin Biochem 1995;32:190-2.
Anne Green * Mary Anne Preece David Hardy
Clinical Chemistry Department West Midlands Regional Laboratory for Neonatal Screening and Inherited Metabolic Disorders Diana, Princess of Wales Children's Hospital Steelhouse Lane Birmingham B4 6NH, United Kingdom
* Author for correspondence. E-mail email@example.com.
Table 1. Blood-spot acylcarnitine abnormalities in seven cases in whom fibroblast fatty acid oxidation was normal. Case Abnormal acylcarnitine findings 1 Increased C12, C14:1, C14:0, C16:1, C20:0, C20:1, and C22:1 2 Increased C6-dicarboxylic and hydroxy-C6-dicarboxylic acids 3 Increased C16; slightly increased C8 4 Slightly increased C8 with minimal autolytic changes 5 Increased C16:1-OH, C16:0-OH, and C18:1-OH 6 Slightly increased C8 with minimal autolytic changes 7 Slightly increased C6, C8, and C10 with minimal autolytic changes
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|Author:||Green, Anne; Preece, Mary Anne; Hardy, David|
|Article Type:||Letter to the editor|
|Date:||Jun 1, 2002|
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