Successful treatment of fetal hemolytic disease due to glucose phosphate isomerase deficiency (<scp>GPI</scp>) using repeated intrauterine transfusions: a case report

Scheltema, P. N. Adama van; Zhang, Ai; Ball, Lynne M.; Steggerda, Sylke J.; Wijk, Richard van; Putte, Dietje E. Fransen van de; Kamp, Inge L. van

doi:10.1002/ccr3.358

Cited by 14 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This clinical pattern is in line with cases previously described by our group (Baronciani et al, 1996); however, in some patients a more severe clinical presentation, i.e., hydrops fetalis, has been reported (Ravindranath et al, 1987; Adama van Scheltema et al, 2015).…”

Section: Discussionsupporting

confidence: 92%

“…The present cohort of GPI deficient patients represents the largest series so far described in a single study, collecting retrospective information and follow-up data over a median period of 18 years. All the cases were never reported before, consistently increasing the number of GPI patients reported in literature (Kugler and Lakomek, 2000; Clarke et al, 2003; Repiso et al, 2006; Warang et al, 2012; Adama van Scheltema et al, 2015; Zhu et al, 2015; Manco et al, 2016; Jamwal et al, 2017; Zaidi et al, 2017; Burger et al, 2018; Kedar et al, 2018; Mojzikova et al, 2018).…”

Section: Discussionmentioning

confidence: 66%

See 1 more Smart Citation

Clinical and Molecular Spectrum of Glucose-6-Phosphate Isomerase Deficiency. Report of 12 New Cases

et al. 2019

View full text Add to dashboard Cite

Glucose-6-phosphate isomerase (GPI, EC 5.3.1.9) is a dimeric enzyme that catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate, the second reaction step of glycolysis. GPI deficiency, transmitted as an autosomal recessive trait, is considered the second most common erythro-enzymopathy of anaerobic glycolysis, after pyruvate kinase deficiency. Despite this, this defect may sometimes be misdiagnosed and only about 60 cases of GPI deficiency have been reported. GPI deficient patients are affected by chronic non-spherocytic hemolytic anemia of variable severity; in rare cases, intellectual disability or neuromuscular symptoms have also been reported. The gene locus encoding GPI is located on chromosome 19q13.1 and contains 18 exons. So far, about 40 causative mutations have been identified. We report the clinical, hematological and molecular characteristics of 12 GPI deficient cases (eight males, four females) from 11 families, with a median age at admission of 13 years (ranging from 1 to 51); eight of them were of Italian origin. Patients displayed moderate to severe anemia, that improves with aging. Splenectomy does not always result in the amelioration of anemia but may be considered in transfusion-dependent patients to reduce transfusion intervals. None of the patients described here displayed neurological impairment attributable to the enzyme defect. We identified 13 different mutations in the GPI gene, six of them have never been described before; the new mutations affect highly conserved residues and were not detected in 1000 Genomes and HGMD databases and were considered pathogenic by several mutation algorithms. This is the largest series of GPI deficient patients so far reported in a single study. The study confirms the great heterogeneity of the molecular defect and provides new insights on clinical and molecular aspects of this disease.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 66%

Clinical and Molecular Spectrum of Glucose-6-Phosphate Isomerase Deficiency. Report of 12 New Cases

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The paper shows 115 modes that could use SAM as an energy source. This may to some extent explain the excessive intake of folic acid in patients with anemia (Adama van Scheltema et al, 2015). Based on the analysis of EFMs, it can be argued that the infrequently mentioned route through SAHH is very important and provides additional opportunities for ATP formation (Schuster & Kenanov, 2005).…”

Section: Discussionmentioning

confidence: 99%

In silico study of peculiarities of metabolism of erythrocytes with glucosephosphate isomerase deficiency

Dotsenko

2019

Regul. Mech. Biosyst.

View full text Add to dashboard Cite

Glucose phosphate isomerase (GPI) deficiency, the third most common cause of hereditary nonspherocytic hemolytic anemia, is associated with the mutation of the GPI gene. The results of the GPI deficiency are premature aging of erythrocytes, macrocytosis, reticulocytosis, minor splenomegaly, hyperbilirubinemia and hyperferritinemia, and hemolytic crisis under the influence of exogenous oxidants such as infections or drugs. Regarding the the lack of GPI correction drugs, the theoretical substantiation of supportive therapy based on system biology approaches that would allow the analysis of the relationships between numerical metabolic processes in a cell would be beneficial. The stoichiometric model of erythrocytes’ steady state metabolism, including the pathways of Embden-Meyerhof and pentose phosphate (PPP), purine metabolism cycles and glutathione synthesis, has been developed. To predict the redistribution of metabolic flows in erythrocytes under conditions of GPI deficiency, we used the flux balance analysis (FBA). In this approach, calculations of the elementary flux modes (EFMs) and the control-effective flux (CEF) have been performed. Using the CEF evaluation approach, effective profiles of enzymatic reactions depending on the degree of enzyme deficiency were obtained. It has been shown that these relationships can be the basis for future experimental studies. Analysis of the profiles of enzymatic reactions of metabolic networks suggests that erythrocytes are capable of metabolizing other substrates that contribute to overcoming the effects of energy stress in the case of enzymopathies. So, it is shown that erythrocytes can effectively use SAM and adenosine as alternative energy sources. It has been established that the GPI enzymopathy results in a decrease in the flow through the glycolysis and pentose phosphate pathway, resulting in a decrease in the content of such reducing agents as NADPH and GSH, ATP. The processes of the GSH synthesis from amino acids in the cell are shown to be suppressed. Decreased content of NADPH and GSH cause the premature aging of erythrocytes. The target therapeutic approaches that influence the behaviour of the metabolic network of erythrocytes are discussed.

show abstract

“…Symptoms are mild-to-severe anemia with fatigue, tachycardia, dyspnea, and pallor. Other symptoms include jaundice, splenomegaly, gallstones, and cholecystitis, and in a few severe cases, it has been shown to cause neurological deficits, hydrops fetalis, and neonatal death [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Glucose phosphate isomerase deficiency demasked by whole-genome sequencing: a case report

Holme,

van Wijk,

Rasmussen

et al. 2024

J Med Case Reports

Self Cite

View full text Add to dashboard Cite

Background Glucose-6-phosphate isomerase deficiency is a rare genetic disorder causing hereditary nonspherocytic hemolytic anemia. It is the second most common glycolytic enzymopathy in red blood cells. About 90 cases are reported worldwide, with symptoms including chronic hemolytic anemia, jaundice, splenomegaly, gallstones, cholecystitis, and in severe cases, neurological impairments, hydrops fetalis, and neonatal death. Case presentation This paper details the case of the first Danish patient diagnosed with glucose-6-phosphate isomerase deficiency. The patient, a 27-year-old white female, suffered from lifelong anemia of unknown origin for decades. Diagnosis was established through whole-genome sequencing, which identified two GPI missense variants: the previously documented variant p.(Thr224Met) and a newly discovered variant p.(Tyr341Cys). The pathogenicity of these variants was verified enzymatically. Conclusions Whole-genome sequencing stands as a potent tool for identifying hereditary anemias, ensuring optimal management strategies.

show abstract

Successful treatment of fetal hemolytic disease due to glucose phosphate isomerase deficiency (GPI) using repeated intrauterine transfusions: a case report

Cited by 14 publications

References 10 publications

Clinical and Molecular Spectrum of Glucose-6-Phosphate Isomerase Deficiency. Report of 12 New Cases

Clinical and Molecular Spectrum of Glucose-6-Phosphate Isomerase Deficiency. Report of 12 New Cases

In silico study of peculiarities of metabolism of erythrocytes with glucosephosphate isomerase deficiency

Glucose phosphate isomerase deficiency demasked by whole-genome sequencing: a case report

Contact Info

Product

Resources

About