THE UNCOMMON CAUSE OF CHRONIC HEMOLİTİC ANEMIA: GLUCOSE PHOSPHATE
ISOMERASE (GPI) DEFICIENCY
Ayşe Gonca Kaçar, Simge Çınar Özel, Burcu Kılınç, Süheyla Ocak and Tiraje Celkan
1. Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Depatment of Pediatric Hematology
and Oncology, Istanbul, Turkey
GPI (glucose phosphate isomerase) deficiency is an inherited disorder that affects red blood
cells. It is one of the rare causes of chronic hemolytic anemia and inherited in autosomal
recessive pattern. Although its prevalence is not known exactly, 50 cases have been reported
in the literature. Two GPI molecules combine to form a homodimer and play a critical role in
the glycolytic pathway in energy production. When GPI remains as a monomer, it provides the
development and maintenance of neuronal cells and is called neuroleukin. Some GPI gene
mutations cause hemolysis by disrupting the enzyme's activity in the glycolytic pathway. Other
GPI gene mutations impair the function of neuronal cells by causing the monomer to break
down more easily. Chronic hemolytic anemia can cause pallor, jaundice, dyspnea, tachycardia,
splenomegaly, and choledocholithiasis.
CASE1:A seven month old male patient was sent to our clinic with mild anemia and jaundice
in the sclera. During the follow-up, moderate reticulocytosis, an increase in indirect bilirubin,
and a decrease in haptoglobulin were found in the patient indicating chronic hemolysis His
one-year-old aunt's daughter also had a history of chronic jaundice and anemia. Physical
examination of the patient revealed mild pallor of the conjunctiva and jaundice of the sclera
and the spleen was palpable. The neuromotor development of the patient was compatible
with his age. Next generation sequencing (NGS) were done for ruling out the other rare causes
of hemolitic anemias. Patient and his cousin had a homozygous c.1009G> A (p.Ala337Thr)
genetic change and they were diagnosed as GPI defficiency.
CASE 2: A 10 day old girl was admitted to the neonatal service due to the detection of
increased phenylalanine in the newborn screening test. She was consulted to us because of
anemia (Hb: 7.6 g / dl htc 21.7) and her sister had a diagnosis of congenital dyserythropoietic
anemia (CDA). On physical examination, she had jaundice and enlarged spleen. Hemogram,
biochemistry, direct coombs, peripheral smear, and mutations of CDA (CDAN1, SEC2B, KIF23)
were done. The corrected reticulocyte level was 4.6%, and direct coombs was negative. She
had four erythrocyte suspension transfusions in four months The sister who was followed up
with a diagnosis of CDA had mild icterus, no splenomegaly. A homozygous c.1009G> A
(p.Ala337Thr) genetic change was detected in the GPI gene by NGS (next generation
sequencing). The patient was diagnosed with glucose phosphate isomerase deficiency, which
is one of the rare causes of nonspherocytic hemolytic anemia, and gene mutation analysis was
done to her sister.The same mutation was detected by genetic analysis (NGS) in our 16-year-old
sister of our patient who was followed up with a diagnosis of CDA for a long time.
We present 2 cases and their two relatives with chronic hemolytic anemia due to GPI
deficiency, which were diagnosed with NGS. This new genetic method ensure early diagnose
of this rare disease and reduce the morbidity and mortality. NGS also provide genetic
counseling for patients.
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