|Year : 2014 | Volume
| Issue : 2 | Page : 229-231
Meenakshi Kalyan1, Shubhangi A Kanitkar1, Anu N Gaikwad1, Harsh Kumar2
1 Department of Medicine, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Vidyapeeth, Pune, Maharashtra, India
2 Department of Pathology, Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Vidyapeeth, Pune, Maharashtra, India
|Date of Web Publication||4-Feb-2014|
Assistant Professor, Department of Medicine, Padmashree Dr D.Y.Patil Medical College, Hospital and Research Centre, Pune
Source of Support: None, Conflict of Interest: None
Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to a fulminant hemolytic anemia. In severe cases, the disorder may present in early childhood, but in some cases it may go unnoticed until later in adult life. We present a 32-year-old male who presented with anemia, jaundice, splenomegaly, and gallstones. Seven of his family members had similar illness in the past. The Mother died of similar illness at the age of 40.
The Blood film showed spherocytosis and reticulocytosis. There was increased osmotic fragility and a negative direct coomb's test. He was given folic acid supplements and was advised for splenectomy and cholecystectomy. This case is reported due to its rarity in Indian population.
Keywords: Gallstones, jaundice, spherocytosis, splenomegaly
|How to cite this article:|
Kalyan M, Kanitkar SA, Gaikwad AN, Kumar H. Hereditary spherocytosis. Med J DY Patil Univ 2014;7:229-31
| Introduction|| |
Hereditary spherocytosis (HS) is a rare inherited red cell membrane disorder that occurs world wide. It is characterized by marked heterogeneity. The estimated prevalence in Caucasian populations ranges from 1:2000 to 1:5000.  HS was described initially in 1871.  In 80% instances, the inheritance of HS is autosomal dominant and in others autosomal recessive.  The molecular defect involves the genes encoding for spectrin, ankyrin, band 3, and protein 4.2.
In North India, both autosomal dominant and recessive patterns have been reported but both have similar presentation to those in other populations but the underlying protein defect in Indian cases has not been characterized yet.  A family history and typical clinical and laboratory findings make the diagnosis possible and additional investigations are not required. 
| Case Report|| |
A 32-year-old single male presented with recurrent and variable yellowish discoloration of eyes of 4 years duration, dragging pain in the left hypochondrium of 1 year duration. He subsequently developed pain in the right hypochondrium, which was intermittent and colicky in nature. He also had exertional breathlessness. No history of fever, neonatal jaundice or blood transfusions, and no alcohol intake. No history of any consanguineous marriage in the family. Seven (7) of his family members were affected with similar symptoms. Family tree is shown in [Figure 1]. Mother had prolonged jaundice and died of similar illness at the age of 40. His three sisters had history of prolonged jaundice and two had undergone splenectomy. His two maternal uncles had history of prolonged jaundice and cholilithiaisis and had undergone cholecystectomy and splenectomy. Further screening of other family members could not be obtained.
First generation information not known
General physical examination revealed height - 167 cm, weight - 55 kg. Afebrile, pale, icteric but no significant peripheral lymphadenopathy. PR - 90/min, BP - 110/70 mmHg RR - 14 breaths/min. No signs of liver cell failure and no sternal tenderness. Abdominal examination revealed hepatomegaly 2 cm below the right costal margins, soft, nontender and splenomegaly of 8 cm from left costal margins, soft and nontender. Rest of the systemic examination was normal.
Laboratory Investigations revealed Hb - 5.8 gm/l, TLC - 4 × 10 9 /L, Platelets - 1604 × 10 9 /l. Peripheral blood smear showed marked anisocytosis, numerous spherocytes (36/high power field), and few abnormally shaped poikilocytes [Figure 2]. Scattered polychromatic cells and late normoblasts 24/100 WBC were seen. WBC show predominance of neutrophils. The total and differential white cell counts were within normal limits. No immature cell of the white cell series were seen. Platelets were adequate on smear and no haemoparasites. Red cell distribution width (RDW) was 48.9 fl. Red cell indices revealed MCHC - 39.3%, MCV - 79.3 fl, MCH - 31.7 pg. Reticulocyte count was 11%, reticulocyte production index was 4.7. Osmotic fragility of incubated blood was markedly increased. Hemoglobin electrophoretic pattern was normal (HbAA). Direct and Indirect coomb's test were negative. Bone marrow aspiration revealed erythroid hyperplasia. Liver function test showed Total bilirubin - 5.0 mg/dl, Indirect bilirubin - 3.9 mg/dl, ALT - 118 IU/l, AST - 98 IU/l, ALP - 117 IU/l, S. LDH - 401 U/l, S. Haptoglobin < 28.3 mg/dl. Serum iron, Ferritin and TIBC were within normal limits. Abdominal ultrasound scan showed hepatosplenomegaly and multiple gallstones largest being 5 mm in diameter. On the basis of anemia, reticulocytosis, increased MCHC and RDW, spherocytosis on the peripheral smear, indirect hyperbilirubinemia and abnormal incubated osmotic fragility test, and positive family history, diagnosis of HS was made.
|Figure 2: High power view of the Romanowsky stained smear showing spherocytes 36 in this high power field. A few poikilocytes are also seen. Spherocytes marked as black arrow and poikilocytes marked as green arrow|
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| Discussion|| |
HS comprises a heterogeneous group of disorders with varying degrees of clinical severity, membrane protein defects and modes of inheritance. Even though rare, it is the most common inherited red cell membrane disorder worldwide.  The abnormal red cell morphology is due to a deficiency or dysfunction in spectrin, ankyrin, band 3, and protein 4.2. Spectrin deficiency is the most common defect. A variety of mutations have been noted in genes encoding these membrane proteins. The genes responsible are localized on chromosomes 1, 2, 8, 15, and 17 for membrane proteins. In pedigrees that have a dominant defect, affected family members tend to have similar degrees of hemolysis and clinical severity. A rapid flow cytometric analysis of eosin-5-maleimide bound to erythrocytes is used as a screening test for the diagnosis of hereditary spherocytosis and for the study of membrane protein deficiency.  The best method for showing reduced membrane surface area of spherocytes is osmotic gradient ekta-cytometry, available only in specialized laboratories. Quantification of the amount of spectrin or ankyrin, band 3 proteins, or protein 4.2 in the erythrocyte membrane is done in atypical cases, which are available only in few specialized laboratories. Disorders in which spherocytes are seen on peripheral blood smear are hereditary spherocytosis, immune hemolytic anemia, acute oxidant injury, microangiopathic and macroangiopathic hemolytic anemia, hemolytic transfusion reactions, thermal injuries, liver disease, hereditary pyropoikilocytosis, clostridial sepsis, zinc toxicity, poisoning with snake, spider, and Hymenoptera envenomations, severe hypophosphatemia, prolonged blood sample storage (in vitro), ABO incompatibility (in neonates), and hypersplenism. 
HS patients are usefully clinically classified as mild, moderate, or severe [Table 1]. 
Source: Patrick G. Gallagher, Bertil Glader: Hereditary spherocytosis, Hereditary Elliptocytosis and other disorders. In John Peer, John Forster et al (Editor). Wintrobe's Clinical Haematology. 12 th Edn, Lippincott Williams and Wilkins, 2009, vol 1: 915
About 20-30% of patients have mild disease, 60-70% have moderate disease, 10% have moderately severe disease, 3-5% of patients have severe disease.  Complications which may develop during the course of illness include gallstones, hemolytic crisis, aplastic crisis, megaloblastic crisis, gout, leg ulcers, extra medullary hemopoiesis, hematological malignancies, cardiomyopathy, hypogonadism. HS in this case report was characterized as severe and patient was advised for a splenectomy and concomitant cholecystectomy.
Splenectomy is very effective in reducing hemolysis, leading to a significant prolongation of the red cell lifespan and should be performed in patients with severe HS, considered in those who have moderate disease, and should probably not be performed in those with mild disease. If splenectomy is done in a patient with symptomatic gallstones, cholecystectomy should be done concomitantly. 
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[Figure 1], [Figure 2]