Synergistic heterozygosity: disease resulting from multiple partial defects in one or more metabolic pathways, 2000, Vockley et al

Inborn errors of metabolism show considerable
variation in the severity of symptoms. This is often
ascribed to the differential effects of specific muta-
tions on gene/enzyme function; however, such geno-
type/phenotype correlations are usually imprecise.
In addition, in some patients with clinical and bio-
chemical findings consistent with a defect in a par-
ticular metabolic pathway, it is ultimately impossi-
ble to arrive at a precise enzymatic diagnosis. In
this situation, we have increasingly been identify-
ing concurrent partial defects in more than one
pathway, or at multiple steps in one pathway. In
this study, we present the clinical, biochemical, and
molecular findings from several patients showing
multiple partial defects in energy metabolism.
These patients show clinical symptoms consistent
with a defect in the affected pathways even though
they do not have a complete deficiency in any one
enzyme. We hypothesize that such patients are ex-
hibiting clinically significant reductions in energy
metabolism related to the compound effects of these
partial defects, a phenomenon we term “synergistic
heterozygosity.” Based on the frequencies of known
disorders of energy metabolism, we propose that
this may represent a previously unrecognized, rel-
atively common mechanism of disease of potentially
great clinical relevance.

https://pubmed.ncbi.nlm.nih.gov/11001791/

 

So hard to get help with this level of complex metabolic stuff. I’m wanting help with ? Galactosemia and ? Glycogen Storage Disorders. Even my Gastroenterologist said he did not have a clue (?) who I would see.
He is interested in knowing my GAL-1-PUT level when I get it… for what it’s worth. My GP ordered the test for me. Lot of it is research, with a focus on kids. Adults are ‘lost to research!’