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| CASE REPORT |
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| Year : 2015 | Volume
: 8
| Issue : 3 | Page : 347-349 |
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Hereditary stomatocytosis: First case report from Valley of Kashmir
Javid Rasool, Fahim Manzoor, Shuaeb Bhat, Nusrat Bashir, Sajad Geelani
Department of Hematology, Sheri Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India
| Date of Web Publication | 15-May-2015 |
Correspondence Address:
Fahim Manzoor
Alamgari Bazar Near Makayas Provisional Store, Nowshera, Srinagar - 190 011, Jammu and Kashmir
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0975-2870.157083
Stomatocytes are erythrocytes with a central slit or mouth-shaped (stoma) area of central pallor when examined on dried smears. In wet preparations, they are uniconcave rather than biconcave, giving them a bowllike appearance. In vitro, stomatocytes are produced by drugs that intercalate into the inner half of the lipid bilayer, thereby expanding the inner lipid surface area relative to that of the outer half of the bilayer. Hereditary stomatocytosis (also known as hereditary hydrocytosis, or overhydrated stomatocytosis) refers to a heterogeneous group of autosomal dominant hemolytic anemias caused by altered sodium permeability of the red cell membrane. We present the first case report of hereditary stomatocytosis in a 10-year-old male from the valley of Kashmir. Only eight families with this condition have been described worldwide. Keywords: Hereditary, stomatocytes
How to cite this article:
Rasool J, Manzoor F, Bhat S, Bashir N, Geelani S. Hereditary stomatocytosis: First case report from Valley of Kashmir. Med J DY Patil Univ 2015;8:347-9 |
| Introduction | |  |
Even among normal individuals a few stomatocytes may be seen in their peripheral blood smears. [1] Acquired stomatocytosis has been associated with acute alcoholism, hepatobiliary disease, vinca alkaloid administration, neoplasms, and cardiovascular disease. Stomatocytosis may also be observed as a processing artifact during peripheral blood film preparation. Stomatocytes are associated with the rare hereditary disorders of red blood cell (RBC) cation permeability known as the hereditary stomatocytosis syndromes, [2] aberrant Rh blood-group antigen expression, sitosterolemia, and familial deficiency of high-density lipoproteins. Each of these stomatocytic disorders is associated with mild to a moderate hemolysis. Hereditary stomatocytosis (also known as hereditary hydrocytosis, or overhydrated stomatocytosis) refers to a heterogeneous group of autosomal dominant hemolytic anemias caused by altered sodium permeability of the RBC membrane. [3] The major pathophysiologic abnormality results from a marked increase in sodium permeability (15-40 times normal) leading to increased RBC sodium, a minor decrease in intracellular potassium, an increase in total monovalent cation content, and thus an increase in intracellular water. Despite a marked compensatory increase of active sodium and potassium transport, increased pump activity is unable to compensate for the markedly increased inward sodium leak.
| Case Report | | |
A 10-year-old male second in the birth order of (2 nd among four male siblings) of a non-consanguineous marriage, presented to the hospital with history of repeated episodes of easy fatigability and pallor since the age of 5 years. He was seen by the haematologist who advised a complete blood count and peripheral blood smear examination. The main findings on physical examination were mild icterus and splenomegaly (3.2 cm below the left costal margin). The complete blood counts revealed hemoglobin of 5.1 g/dl, RBC count of 2.1 million/cmm and packed cell volume 28%, mean corpuscular volume (MCV) of 132 fl, mean corpuscular hemoglobin concentration (MCHC) of 18.2 g/dl. Peripheral blood smear examination showed reduced red cell density with polychromasia. Few target cells, anisopoikilocytosis and erythrocytes having a central mouthlike or "stoma" appearance [Figure 1]. The (total) bilirubin levels were 3.2 mg/dl, conjugated bilirubin 0.8 mg/dl, uncongugated bilirubin 2.4 mg/dl. Corrected reticulocyte count was 2.2%. A provisional diagnosis of hemolytic anemia was made. The patient was treated symptomatically with hematinics and was regularly seen every week on followup. The subsequent peripheral smear examination showed persistence of erythrocytes with stomatocytes. Detailed drug intake history did not implicate any drug. Family history revealed similar clinical picture in the other three male siblings as well though not as severe [Figure 2]. The peripheral blood smear examination of the siblings showed similar abnormal appearing erythrocytes [Figure 3]. A provisional diagnosis of hereditary stomatocytosis was considered. A screening of both the parents was done and the peripheral blood smear of the mother revealed similar stomatocytes [Figure 4]. Patient's intracellular potassium concentration was 100 mEq/L (n = 140 mEq/L) and intracellular Na concentration was 40 mEq/L (n = 12 mEq/L). | Figure 2: Family tree demonstrating mother and all four male sibling affected
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| Discussion | | |
Stomatocytes are red cells with a central slit like are of pallor. In the normal population stomatocytes of up to 5% can be seen in the peripheral blood smear and in a case of hereditary stomatocytosis >30% of the red cells on peripheral blood smear show this morphology.
Hereditary stomatocytosis is a rare autosomal dominant disorder characterised by increased permeability to sodium and potassium leading to overhydration of RBC. The overhydrated stomatocytes are susceptible to osmotic mechanical lysis. In most patients, excess cation permeability is associated with the absence of red cell membrane protein band 7 on sodium dodecyl sulfate gels. This protein is referred to as band 7.2b or stomatin, [4],[5],[6] and its function is currently unknown. No abnormalities in the stomatin gene, which has been isolated and cloned, have been identified in stomatin-deficient individuals with hereditary stomatocytosis. Homozygous knockout mice that completely lack the murine analog of erythrocyte stomatin exhibit no features of the hereditary stomatocytosis syndrome seen in humans, suggesting that stomatin deficiency is not the proximate cause of the disease in humans, although it may be a marker for another membrane defect that is responsible. [7]
The severity of hemolytic disease is diverse, both between different families and among affected members of the same family. In most patients, symptoms-related to intermittent anemia and jaundice are so mild that no therapy is required. Rarely, the anemia is of sufficient severity to require blood transfusion therapy. Splenomegaly is an expected consequence of hemolytic anaemia due to its function of removing abnormal red cells. Approximately 10-50% of circulating red cells are stomatocytes in hereditary stomatocytosis. The MCV is elevated, often strikingly, the MCHC is normal or low (as a result of increased cell water content), and osmotic fragility is increased. Red cell sodium content is increased, and potassium content is decreased. In most patients, hemolytic anemia is improved after splenectomy, but splenectomy is considered contraindicated in most cases because there is a high risk of postsplenectomy thromboembolic disease and chronic pulmonary hypertension. This has been attributed to increased erythrocyte-endothelial cell adhesion resulting from increased phosphatidylserine exposure of overhydrated erythrocytes. [8] Fortunately, most patients have compensated hemolysis and splenectomy is not required.
| Conclusion | | |
To the best of our knowledge, this is the first case report of hereditary stomatocytosis from the valley of Kashmir. The family history from the mother and the clinical features are in keeping with classical hereditary stomatocytosis. Even though, only eight families with this condition have been described worldwide. We urge clinicians working in this environment to have a high index of clinical suspicion when managing cases of chronic mild anaemia.
| References | | |
| 1. | Davidson RJ, How J, Lessels S. Acquired stomatocytosis: Its prevalence of significance in routine haematology. Scand J Haematol 1977;19:47-53.  [ PUBMED] |
| 2. | Mentzer WC Jr, Smith WB, Goldstone J, Shohet SB. Hereditary stomatocytosis: Membrane and metabolism studies. Blood 1975;46:659-69. [ PUBMED] |
| 3. | Delaunay J. The hereditary stomatocytoses: Genetic disorders of the red cell membrane permeability to monovalent cations. Semin Hematol 2004;41:165-72. |
| 4. | Fricke B, Argent AC, Chetty MC, Pizzey AR, Turner EJ, Ho MM, et al. The "stomatin" gene and protein in overhydrated hereditary stomatocytosis. Blood 2003;102:2268-77. |
| 5. | Fricke B, Parsons SF, Knöpfle G, von Düring M, Stewart GW. Stomatin is mis-trafficked in the erythrocytes of overhydrated hereditary stomatocytosis, and is absent from normal primitive yolk sac-derived erythrocytes. Br J Haematol 2005;131:265-77. |
| 6. | Lande WM, Thiemann PV, Mentzer WC Jr. Missing band 7 membrane protein in two patients with high Na, low K erythrocytes. J Clin Invest 1982;70:1273-80. [ PUBMED] |
| 7. | Zhu Y, Paszty C, Turetsky T, Tsai S, Kuypers FA, Lee G, et al. Stomatocytosis is absent in "stomatin"-deficient murine red blood cells. Blood 1999;93:2404-10. |
| 8. | Gallagher PG, Chang SH, Rettig MP, Neely JE, Hillery CA, Smith BD, et al. Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis. Blood 2003;101:4625-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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