Two cases of red cell aldolase deficiency associated with hereditary hemolytic anemia in a japanese family

Abstract

Two cases of red cell aldolase deficiency associated with congenital nonspherocytic hemolytic anemia are reported. The proband is a fourteen-month-old Japanese boy. Consanguineous marriage was not proven but probable in this family, as the parents were born in the same small island. The proband had moderate to mild anemia aggravated by upper respiratory infections, 1 cm hepatomegaly and 2.5 cm splenomegaly, but was unremarkable in other respects and has thus far not shown mental or growth retardation. He did not have dysmorphic features. The red cell aldolase activity was 6% of the normal mean. The enzyme was unstable with respect to heat, and Km for fructose 1,6-diphosphate (F-1,6-DP) was high. The parents and other heterozygotes showed intermediate activity between that of the proband and that of normal subjects. Red cell F-1,6-DP concentration in this case was remarkably increased. Red cell glucose consumption, and lactate formation, as well as hexose monophosphate shunt activity, were decreased as compared with a comparable reticulocyte-rich hereditary spherocytosis patient. Hexose monophosphate dehydrogenase by a high concentration of F-1,6-DP in his red cells. As a result of family study, another homozygous aldolase deficiency case associated with hemolytic anemia was found. He is 13 years old and a nephew of the proband's paternal grandmother. His hemolytic anemia also is moderate to mild and aggravated by upper respiratory infections. He does not seem to have mental or growth retardation, nor does he possess dysmorphic features.

The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis

“…Enzyme stability was decreased in a male patient described by Beutler et al 46 In addition to hemolytic anemia, this patient also displayed mental retardation and dysmorphic features. 46 The 2 patients reported by Miwa et al 47 suffered from severe hemolytic anemia, exacerbated by infection, but none of the features described by Beutler et al In one of these patients the causative mutation concerned a homozygous substitution of aspartic acid to glycine at residue 128. 51 The patient reported by Kreuder et al 48 suffered from hemolytic anemia, myopathy, and psychomotor retardation.…”

“…45 Aldolase deficiency (OMIM 103 850) is a very rare disorder and only 6 patients from 5 families have been described. [46][47][48][49][50] Patients all displayed moderate chronic hemolytic anemia. Enzyme stability was decreased in a male patient described by Beutler et al 46 In addition to hemolytic anemia, this patient also displayed mental retardation and dysmorphic features.…”

Human aldolase isozyme gene: the structure of multispecies aldolase B mRNAs

“…Since animal aldolase isozyme appears to be an useful system to elucidate (i) the regulatory mechanism of tissue-specific gene expression in eukaryotic cells, (ii) the molecular mechanism of the fructose intolerance or other hereditary diseases related to aldolase gene functions in man (2,3) and also (iii) the evolution of isozyme genes, we have focused our study on the structural analysis of aldolase isozyme genes and the transcripts in rat and human. In the previous papers we had characterized cDNAs for rat aldolase A (4) and B (5, 6) mRNAs and genomic structure of rat aldolase B gene (7).…”

Acute rhabdomyolysis

“…Четвертичная структура фермента, также как и мутации, способствует термола-бильности [45]. Сходная термолабильность обнаруже-на при более высоких температурах и в эритроцитах [39,40,46] и проанализирована методом расчета ста-бильности белка [35]. Возможно, в связи с тем, что эри-троциты широко представлены в ткани крови, они более устойчивы к внешним факторам, чем миобласты [47].…”