The most common and also the most fatal mutation is the Glu104Asp (Glu105Asp if the first Met is counted) caused by a G-C transversion in codon 104. The above-mentioned clinical features are the most expressed in this case. This mutation causes the instability of the TPI homodimer (it is located at the interface of the subunits). More than half of the recognized cases was caused by this mutation. There are many others; the symptoms are usually milder. From biochemical point of view, the main characteristics are the significantly decreased triosephosphate isomerase activity (5-20%), and the elevated dihydroxy-acetone phosphate level. The activity is easily measurable. Of course, genetic identification of the mutation is necessary.
TPI1