Hyperammonemia in Russia Due to Carbonic Anhydrase VA Deficiency Caused by Homozygous Mutation p.Lys185Lys (c.555G>A) of the CA5A Gene

Abstract

Hyperammonemia due to carbonic anhydrase VA deficiency (OMIM# 615751) is a rare, life-threatening hereditary disease caused by biallelic mutations in the CA5A gene, presenting as encephalopathic hyperammonemia of unexplained origin during the neonatal period and infancy. Here, we present a detailed description of a 5-year-old patient with the homozygous mutation p.Lys185Lys (c.555G>A) in the CA5A gene. This variant was previously described by van Karnebeek et al. in 2014 in a boy of Russian origin. We found a high frequency of carriers of this mutation in Russia; 1:213, which is 7 times higher than the expected frequency calculated based on data on Western European populations. Thus, targeted testing for the mutation p.Lys185Lys (c.555G>A) in the CA5A gene should be useful for early detection by selective screening in neonatal intensive care units.

Progress of Section “Biochemistry” in 2022

“…A relevant number of papers dealing with this enzyme, its inhibitors, activators and involvement in various diseases have been published in 2022 in this journal [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. The first group of contributed materials dealt with the use of this protein for investigations of basic biochemical approaches, such as protein folding [ 7 ], thermodynamic parameters assessment for protein–ligand interactions [ 8 ], bioluminescence resonance energy transfer connected to the binding of the metal ion to apoenzymes [ 9 ], the possibility to evidence chalcogen bonds in the X-ray crystal structures of CA–lig and adduct [ 10 ].…”

“…The role of the genetic deficiency of the mitochondrial enzyme CA VA which causes hyperammonemia in the affected patients has also been investigated [ 26 ] as well as the role of immune checkpoint blockade on the anticancer effects of CA IX chimeric antigen receptor T cells [ 27 ]. A comprehensive review on CAs present in the model organism zebra fish has also been published by Parkkila’s group [ 28 ].…”