Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency

@article{Kugler1998MolecularBO,
  title={Molecular basis of neurological dysfunction coupled with haemolytic anaemia in human glucose-6-phosphate isomerase (GPI) deficiency},
  author={Wilfried Kugler and K. Breme and Petra Laspe and Hilary Muirhead and Christopher Davies and Heinz Winkler and Werner Schr{\"o}ter and Max Lakomek},
  journal={Human Genetics},
  year={1998},
  volume={103},
  pages={450-454}
}
Glucose-6-phosphate isomerase (GPI) deficiency, an autosomal recessive genetic disorder with the typical manifestation of nonspherocytic haemolytic anaemia, can be associated in some cases with neurological impairment. GPI has been found to be identical to neuroleukin (NLK), which has neurotrophic and lymphokine properties. To focus on the possible effects of GPI mutations on the central nervous system through an effect on neuroleukin activity, we analysed DNA isolated from two patients with… 
Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction
TLDR
It is suggested that neuromuscular impairment with hemolytic anemia cases could be investigated for p.Arg347His pathogenic variant causing GPI deficiency because of neuroleukin activity present in the GPI monomer which has neuroleokin action at the same active site and generates neurmuscular problems as well as hemolytics anemia.
Clinical, laboratory, and mutational profile of children with glucose phosphate isomerase deficiency: a single centre report
TLDR
It is reported that neonatal jaundice, macrocytosis and high prevalence of p.Arg347His variant were predominant in GPI deficiency with prominent lack of neurological manifestations, and the benefits of splenectomy and the need for genetic counseling are emphasized.
Clinical and Molecular Spectrum of Glucose-6-Phosphate Isomerase Deficiency. Report of 12 New Cases
TLDR
This study reports the clinical, hematological and molecular characteristics of 12 GPI deficient patients from 11 families, with a median age at admission of 13 years, and identifies 13 different mutations in the GPI gene, six of them never been described before.
Attenuation of Hemolysis Due to Glucose-6-Phosphate Isomerase Deficiency With Ketogenic Diet – A Case Report
TLDR
The case highlights some interesting insights into likely pathogenic mechanisms of the enzyme deficiency of a South Asian female child homozygous for the novel p.Leu425Phe with progressive neuromuscular deficit, intractable seizures, short-lived transfusion dependence and preferential hepatic iron overload.
Hemolytic Anemia and Neurological Manifestations – An Uncommon Combination
TLDR
Evaluation of non-spherocytic hemolytic anemia in pediatric age group, warrants a thorough neurological evaluation to identify individuals with rare erythrocytic enzymopathies, and GPI deficiency being relatively more common, should be considered as a probable diagnosis.
Glucose-6-phosphate isomerase deficiency.
TLDR
This chapter reviews the clinical pattern of the condition; biochemical and molecular studies; structure-function relationships; the molecular basis of neurological dysfunctions sometimes associated with GPI deficiency; and the correlation between the severity of the anaemia and the molecular defect.
Molecular diagnosis of unexplained haemolytic anaemia using targeted next-generation sequencing panel revealed (p.Ala337Thr) novel mutation in GPI gene in two Indian patients
TLDR
This rapid and high-performance targeted NGS assay can be configured to detect specific CHA mutations unique to an individual defect, making it a potentially valuable method for diagnosis of unexplained haemolytic anaemia.
...
...

References

SHOWING 1-10 OF 25 REFERENCES
Glucose phosphate isomerase deficiency: biochemical and molecular genetic studies on the enzyme variants of two patients with severe haemolytic anaemia
TLDR
Biochemical and molecular genetic studies performed on the enzyme variants of two patients compound heterozygous for glucose phosphate isomerase (GPI) deficiency and GPI `Nordhorn' showed that in both cases the simultaneous occurrence of a single amino acid sub‐stitution affecting the active site probably explains the severe clinical course of the disease.
Combination of congenital nonspherocytic haemolytic anaemia and impairment of granulocyte function in severe glucosephosphate isomerase deficiency. A new variant enzyme designated GPI Calden.
TLDR
Investigations revealed that isolated granulocytes of both siblings show marked reduction of bactericidal activity and decreased production of superoxide anion, indicating that impairment of granulocyte function might be a more general feature of severe GPI deficiency than formerly noted.
Glucosephosphate isomerase (GPI) deficiency mutations associated with hereditary nonspherocytic hemolytic anemia (HNSHA).
TLDR
It is suggested that heterozygosity for GPI confers little if any selective advantage and the 489 G/A polymorphism in the GPI coding region was used to demonstrate unequivocally that the 1039 C-->T mutation occurred in both haplotypes and therefore probably originated more than once.
Congenital haemolytic anaemia resulting from glucose phosphate isomerase deficiency: genetics, clinical picture, and prenatal diagnosis.
TLDR
Examination of amniotic cells obtained by amniocentesis on the mother at 28 weeks in her second pregnancy led to the prenatal diagnosis of GPI deficiency, and a 'compound' heterozygote at the GPI locus indistinguishable from the first child was successfully treated by immediate exchange transfusion and subsequent blood transfusions.
Haematological studies in a new variant of glucosephosphate isomerase deficiency (GPI Utrecht).
TLDR
Though the defect was generalized, no disturbance in granulocyte and thrombocyte functions were detected and extensive studies on mechanisms involved in drug-sensitive haemolytic anaemia did not reveal its causes.
Haematological studies in a new variant of glucosephosphate isomerase deficiency (GPI Utrecht).
TLDR
Though the defect was generalized, no disturbance in granulocyte and thrombocyte functions were detected and extensive studies on mechanisms involved in drug-sensitive haemolytic anaemia did not reveal its causes.
The first stable variant of erythrocyte glucose‐phosphate isomerase associated with severe hemolytic anemia
TLDR
A new variant of glucosephosphate isomerase (GPI) associated with hemolytic anemia, mental retardation, and muscular hypotonia is described, the first example of the association of a stable mutant GPI with severe hemolytics anemia.
The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia.
TLDR
DNA was isolated from four unrelated glucose phosphate isomerase-deficient patients and six mutations were found to involve highly conserved amino acids of glucose phosphateIsomerase, suggesting that these residues are crucial for the maintenance of biological activity.
Functional interaction and partial homology between human immunodeficiency virus and neuroleukin.
TLDR
The inhibition by HIV-1 of neuron growth in the presence of NLK was found to be due to the gp120 envelope glycoprotein, and regions of sequence homology between gp120 and NLK may account for this inhibitory property of gp120.
The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase
TLDR
Molecular clones of NLK have been expressed in monkey COS cells and the product was shown to have the same biological and biochemical properties as the extracted protein, and its amino-acid sequence is 90% homologous to the sequence of mouse neuroleukin.
...
...