title: Sudden infant death syndrome and abnormal metabolism of thiamin.
abstract: Although it has been generally accepted that moving the infant from the prone to the supine position has solved the problem of sudden infant death syndrome (SIDS), it has been hypothesized that this is an insufficient explanation and that a mixture of genetic risk, some form of stressful incident and marginal brain metabolism is proportionately required. It is suggested that each of these three variables, with dominance in one or more of them, act together in the common etiology. Much has been written about the association of thiamin and magnesium but the finding of extremely high concentrations of serum thiamin in SIDs victims has largely caused rejection of thiamin as being involved in the etiology. The publication of abnormal brainstem auditory evoked potentials strongly suggests that there are electrochemical changes in the brainstem affecting the mechanisms of automatic breathing and the control of cardiac rhythm. The brainstem, cerebellum and limbic system of the brain are known to be highly sensitive to thiamin deficiency (pseudo-hypoxia) and the pathophysiology is similar to a mild continued deprivation of oxygen. Little attention has been paid to the complex metabolism of thiamin. Dietary thiamin requires the cooperation of the SLC19 family of thiamin transporters for its absorption into cells and recent information has shown that transporter SNPs may be relatively common and can be expected to increase genetic risk. Thiamin must be phosphorylated to synthesize thiamin pyrophosphate (TPP), well established in its vital action in glucose metabolism. TPP is also a cofactor for the enzyme 2-hydroxyacyl-CoA lyase (HACL1) in the peroxisome, emphasizing its importance in alpha oxidation and plasmalogen synthesis in cell membrane physiology. The importance of thiamine triphosphate (TTP) in energy metabolism is still largely unknown. Thiamin metabolism has been implicated in hyperemesis gravidarum and iatrogenic Wernicke encephalopathy has been reported when the patient is treated with hyperalimentation, in spite of the pharmaceutical doses of thiamin in the intravenous fluid. Defective glucose metabolism, the vital fuel for energy synthesis, particularly in brain, must affect the developing fetus and the pattern of subsequent neonatal health. Sudden death in an apparently healthy infant, occurring at 3-4months, has long been known to result from feeding the infant with thiamin deficient breast milk. The early investigators of the cause of beriberi considered that this form of sudden death was pathognomonic of the infantile form of the disease.
authors.affiliation: Associate Emeritus, Cleveland Clinic Foundation, Cleveland, OH, United States. Electronic address: derricklonsdale@hotmail.com.
authors.forename: Derrick
authors.initials: D
authors.lastname: Lonsdale
mesh_terms: D000293:Adolescent; D001933:Brain Stem / Q000503:physiopathology; D019755:Carbon-Carbon Lyases; D002462:Cell Membrane / Q000378:metabolism; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005072:Evoked Potentials, Auditory; D023281:Genomics; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D007223:Infant; D054972:Postural Orthostatic Tachycardia Syndrome / Q000503:physiopathology; D054969:Primary Dysautonomias / Q000503:physiopathology; D013315:Stress, Psychological; D013398:Sudden Infant Death; D013831:Thiamine / Q000097:blood / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000503:physiopathology; D013835:Thiamine Pyrophosphate / Q000378:metabolism; D014611:Vaccination
chemical_list: D019755:Carbon-Carbon Lyases; C561547:HACL1 protein, human; D004746:Enoyl-CoA Hydratase; D005947:Glucose; D013835:Thiamine Pyrophosphate; D013831:Thiamine