AUTHORS: Gariani K, Klauser A, Vargas MI, Lazeyras F, Tran C

Brain Sciences, 2022(12): 389, March 2022


Hyperinsulinism/hyperammonemia syndrome (HI/HA) is an autosomal dominant disorder
caused by monoallelic activating mutations in the glutamate dehydrogenase 1 (GLUD1) gene.
While hyperinsulinism may be explained by a reduction in the allosteric inhibition of GLUD1, the
pathogenesis of HA in HI/HA remains uncertain; interestingly, HA in the HI/HA syndrome is not
associated with acute hyperammonemic intoxication events. We obtained a brain magnetic resonance
(MR) in a woman with HI/HA syndrome with chronic asymptomatic HA. On MR spectroscopy,
choline and myoinositol were decreased as in other HA disorders. In contrast, distinct from other HA
disorders, combined glutamate and glutamine levels were normal (not increased). This observation
suggests that brain biochemistry in HI/HA may differ from that of other HA disorders. In HI/HA,
ammonia overproduction may come to the expense of glutamate levels, and this seems to prevent
the condensation of ammonia with glutamate to produce glutamine that is typical of the other HA
disorders. The absence of combined glutamate and glutamine elevation might be correlated to the
absence of acute cerebral ammonia toxicity.

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