2006 paper on Isovaleric Acidemia : 'sweaty feet syndrome'

Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity

Vockley J, Ensenauer R
Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh

Note: This editorial is the writers opinionin the murky world of metabolic body odor and halitosis, you have to wonder if in reality this means they will have no problems except with transient 'sweaty feet odor' that never seems to be around when a doctor is present

This is an interesting paper because the 'rules' for isovaleric acidemia were rigidly set (2 kinds: both serious and obvious) until a blood check of a sample normal population (neonatal babies) was taken and there was found to be a 3rd group who the researchers deemed to be, so far, 'asymptomatic' (without problems). However, in the murky world of metabolic body odor and halitosis, you have to wonder if in reality this means they will have no problems except with transient 'sweaty feet odor' that never seems to be around when a doctor is present. You have to wonder if the same may be true if a 'spot-check' of blood/DNA was taken amongst a sample normal population for any form of metabolic body odor and/or halitosis, depending on whatever enzymes or compounds are involved, including the possibly most common; fecal body odor.

Also, of interest is the use of the word 'heterogeneity'. Presumably they mean the mild cases in the study had 2 known mutants or variants of different type, rather than 2 mutants of the same type (autosomal recessive ?). It looks as if this is similar as to how the loosening of the genetic rule on trimethylaminuria may go, still taught as autosomal recessive, although testers seem to be going towards it being heterogenous ... and possibly both health problems will turn out autosomal dominant for 'mild' cases (if you think transient smelling is mild).

...Initially, two phenotypes with either an acute neonatal or a chronic intermittent presentation were described. More recently, a third group of individuals with mild biochemical abnormalities who can be asymptomatic have been identified through newborn screening of blood spots by tandem mass spectrometry. IVD is a flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers electrons to the electron transfer flavoprotein. Human IVD has been purified from tissue and recombinant sources and its biochemical and physical properties have been extensively studied. Molecular analysis of the IVD gene from patients with IVA has allowed characterization of different types of mutations in this gene. One missense mutation, 932C>T (A282V), is particularly common in patients identified through newborn screening with mild metabolite elevations and who have remained asymptomatic to date. This mutation leads to a partially active enzyme with altered catalytic properties; however, its effects on clinical outcome and the necessity of therapy are still unknown. A better understanding of the heterogeneity of this disease and the relevance of genotype/phenotype correlations to clinical management of patients are among the challenges remaining in the study of this disorder in the coming years.

REFERENCE: National Center for Biotechnology Information (NCBI) at the U.S. Library of Medicine (NLM)

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related links
http://ghr.nlm.nih.gov/condition=isovalericacidemia