If science were art and art were science, then the howling black wolf has probably swallowed some N-(4-hydroxyphenyl)ethanamide.
Do you love the sweet, caramel-like smell of male syrup? I know I love it to go with my pancakes. But, do you love it so much you’d like your body fluids to smell like maple syrup? Great! But if you do, that might actually mean you suffer from a rare and fatal genetic defect called Maple Syrup Urine Disease (or MSUD, for short). (Yay?)
The genetic defect is so named after its tell-tale symptom of characteristic, sweet smeling body secretions like urine, sweat, and earwax that is oddly reminiscent of maple syrup. The substance responsible for the smell is sotolone (or 4,5-dimethyl-3-hydroxy-2[5H]-furanone for them sciency types), which is also present in the herbs lovage and fenugreek. Curiously, in areas with milder climates where maple syrup is not as available, the disease is associated with fenugreek instead. As descriptions are subjective, some attribute the smell to malt, Maggi (a brand of seasoning), or even curry. Indeed, the sotolone in low concentrations smell more like maple syrup but smells more and more like curry as the concentration increases.
The genetic defect per se is located in chromosome 19; it is a mutation that disrupts the proper encoding of the four protein subunits (termed E1α, E1β, E2, and E3) that together constitute the branched-chain alpha-keto acid dehydrogenase complex (BCKDC). A deficiency of the enzyme complex leads to the build-up of branched chain amino acids leucine, isoleucine, and valine and their consequential toxic by-products since the enzyme is not sufficiently present to break these down. In fact, sotolone (responsible for the smell) is a metabolite of isoleucine. This means that the patients suffering from the defect probably have delicious smelling laundry but this also means that they are likely going to die – after struggling with severe brain damage first, of course. Other symptoms of the condition may include low appetite, dehydration, low blood sugar, seizures, low blood pH, weakness, abnormal arching of the spine, inflammation of the pancreas, and coma.
The condition is genetic but, more precisely, it follows the pattern of autosomal recessive inheritance which means that the patient would need two copies of the gene for the symptoms to show. An individual might carry one copy of the gene but is unaffected – this individual is hence called a carrier. A person with the condition therefore inherited the two copies of the gene form his/her parents – one gene from each parent. MSUD is most likely in individuals of Mennonite, Amish, and Jewish ancestry.
All is not lost, however, for a person afflicted with MSUD. The patient can avoid death and lead a “normal” life provided that he/she follow a strict diet to avoid food stuffs containing the amino acids leucine, isoleucine, and valine – foods like eggs, soy protein, seaweed, fish, and fowl meats; take food supplements that substitute for the metabolic functions of these amino acids; and regular blood testing.
Burtis, C. A.; Ashwood, E. R.; and Bruns, D. E. Newborn screening and inborn errors of metabolism. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th ed. Elsevier Health Sciences, December 2011.
Li, J; Machius, M; Chuang, JL; Wynn, RM; and Chuang, DT (2007).“The two active sites in human branched-chain alpha-keto acid dehydrogenase operate independently without an obligatory alternating-site mechanism.” The Journal of Biological Chemistry 282 (16): 11904-13.
Podebrad, F.; Heil, M ; Reichert, S; Mosandl, A; Sewell, AC; and Böhles, H (1999). “4,5-Dimethyl-3-hydroxy-2[ 5H] – furanone (sotolone) – The odour of maple syrup urine disease.” Journal of Inherited Metabolic Diseases 22 (2): 107-114.
Puffenberger, EG (2003). “Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania.” American Journal of Medical Genetics: Part C, Seminars in Medical Genetics
121c (1): 18-31.
[Post by Deo Mostrales]