Disease-modifying influences of coexistent G6PD-deficiency, Gilbert syndrome and deletional alpha thalassemia in hereditary spherocytosis: A report of three cases.
BACKGROUND
Hereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by heterogeneous clinical presentations with variable degrees of anemia, jaundice, splenomegaly and gallstones. Although the underlying genetic defects in red cell membrane proteins may explain many phenotypic variations, a proportion of variability may be due to other co-inherited factors like enzymopathies, thalassemias and Gilbert syndrome. Associations of HS with glucose-6-phosphate dehydrogenase (G6PD) deficiency and Gilbert syndrome in isolation have been reported previously.


METHODS
We describe 3 adult cases of HS with concomitant Gilbert syndrome and G6PD-Mediterranean mutations (2 hemizygous males, aged 15 and 35y and 1 heterozygous 25-y female).


RESULTS
Two patients required multiple transfusions that required splenectomy for management. One patient (15y male) also carried the single gene alpha 4.2 deletion and was less symptomatic.


CONCLUSIONS
These cases illustrate the importance of clinico-pathological correlation and judicious extended testing for various contributing factors that may modify the clinical course of HS patients. G6PD deficiency is also a common enzymopathy in India and can contribute to the phenotypic heterogeneity. Its recognition is important for advising avoidance of oxidizing drug exposure.
Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: manujamwal25@gmail.com.
Manu
M
Jamwal
Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: aggarwalanu2011@gmail.com.
Anu
A
Aggarwal
Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: verinderkumar@gmail.com.
Verinder
V
Kumar
Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: prashant.sh@gmail.com.
Prashant
P
Sharma
Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: drmanupdeshpgi@yahoo.co.in.
Man Updesh Singh
MU
Sachdeva
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: deepakbansaldr@gmail.com.
Deepak
D
Bansal
Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: malhotrapankaj@hotmail.com.
Pankaj
P
Malhotra
Department of Hematology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: das.reena@pgimer.edu.in.
Reena
R
Das
D000293:Adolescent; D000328:Adult; D005260:Female; D005878:Gilbert Disease / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D017384:Sequence Deletion; D013103:Spherocytosis, Hereditary / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics*
Alpha gene deletion; Gilbert syndrome; Glucose-6-phosphate dehydrogenase deficiency; Hereditary spherocytosis