Reported cases of Aldolase A deficiency with the described mutations.

<p>*: normal range. In the first case reported by Beutler et al in 1973 with no described mutation, the red cell aldolase activity was 16% of normal mean.</p><p>Reported cases of Aldolase A deficiency with the described mutations.</p

1A: Family tree showing the 3 affected children.

<p>1B: Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate (isoenzyme A, PDB code 4ALD) superimposed with the tetrameric crystal structure of human brain aldolase (isoenzyme C, PDB code 1XFB), which is similar to the muscle isoenzyme. Chains A, B, C and D of isoenzyme C are shown in orange, light blue, light green and pink, respectively. Monomeric isoenzyme A is shown in grey and is superimposed on chain D of the tetrameric isoenzyme C. Fructose 1,6-bisphosphate co-crystallized with isoenzyme A is shown in yellow. The mutated residue described in this report (red arrow) and the mutated amino acids previously described are highlighted in the magnified structure. The structural and functional consequences of the mutations are described in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004711#pgen-1004711-t001" target="_blank">Table 1</a>. 1C: aldolase A, glucose-6-phosphate dehydrogenase (G6PD) and hexokinase activities in the erythrocytes of the parents, the healthy sibling and the 3 affected patients (*: patients 2, 3, 4). 1D: in vitro muscle study of anaerobic glycogenolysis and glycolysis (only patient 3); results of lactate production (µmol/g muscle in 30 minutes) after incubation with various substrates.</p

<i>ALDOA</i> expression and activity.

<p>3A:<i>ALDOA</i> mRNA expression in control myoblasts (C, white bars) and the patient myoblasts (P, grey bars) under basal conditions, with TNFα+Ilβ treatment (left) or at a high temperature (right, 40°C); Aldolase A protein levels (lower panel) under basal conditions, with TNFα+Ilβ treatment or at a high temperature. 3B: Aldolase A activity in control and the patients' myoblasts under the same conditions: basal conditions, TNFα+Ilβ treatment and at different temperatures. The results are shown as the mean value ±SD from 3 independent experiments. 3C: Aldolase A activity in control and patients erythrocytes under basal conditions and at different temperatures. The results are shown as the mean value of two independent experiments. 3D: Aldolase A activity (upper) and protein level (below) in the patient myoblasts under basal condition and after arginine (Arg) treatment.*: p<0,05).</p