CASE REPORTRare Case of Hemophagocytic Disorder: A Family WithChediak Higashi SyndromeWAQAR HUSSAIN, ANITA LAMICHHANE, MOHAMMAD ASLAM------------------------------------------------------------------ Pak Paed J 2012; 36(1): ABSTRACTAuthor’s affiliations------------------------------------------- Chediak Higasi syndrome (CHS) is an autosomal recessive disorder characterized by partial occulocutaneous albinism, increasedCorrespondence to: susceptibility to infection, photophobia, a mild bleeding diathesis and a tendency to develop a life-threatening lymphoma like syndrome. ManyProf. Waqar Hussain similar cases of this disease with some additional features have beenDepartment of Pediatrics, described in the national and international journals. Pancytopenia,Shaikh Zayed Hospital, hepatosplenomegaly, lymphohistiocytic infiltration in bone marrow andLahore. Pakistan the abnormal characteristic granules in leukocytes lead to the diagnosis in the reported case.E-mail:firstname.lastname@example.org KEY WORDS: Chediak –Higashi syndrome, occulocutaneous albinismINTRODUCTION The CHS gene was identified in 1996 and has been mapped onto chromosome 1q42-q44 (8), aChediak-Higashi syndrome (CHS) was described region codes for a protein known as lysosomalby Beguez Cesar in 1943, Steinbrinck in 1948, trafficking regulator5.Chediak in 1952, and Higashi in 19541. Chediak-Higashi syndrome is a rare lysosomal disorder CASE REPORTwhich is characterized by incompleteocculocutaneous hypopigmentation, photo- A nine years old girl, resident of Lahore, a productphobia, nystagmus, large eosinophilic peroxidase of consanguineous marriage, developmentallypositive inclusion bodies in the myeloblasts and normal, a student of class V, presented withpromyelocytes of the bone marrow, neutropenia history of progressive abdominal distension for theand an abnormal susceptibility to cutaneous and last six years and progressive pallor for the last 15respiratory infections2. days. The child had some febrile illness two weeks back. There was no history of petechiae, bruises,About 50% to 85% of patients eventually enter an recurrent chest and skin infections, or boils. Noaccelerated phase, manifested by fever, history of blood transfusion in the past. Anotherlymphadenopathy, anemia, jaundice, neutro- sibling succumbed at the age of 3 years withpenia, thrombocytopenia, and widespread similar complaints. There was death of two otherlymphohistiocytic organ infiltrates3. This lymphoma siblings in the family at 4 months and 8 months oflike stage is precipitated by viruses, particularly by life respectively.infection with Epstein-Barr virus. It is associatedwith anemia, bleeding episodes, and On examination, she was extremely pale withoverwhelming infections leading to death1. erythematous rash over her face. Her growthMorbidity results from patients succumbing to parameters were below 3rd centiles. She hadfrequent bacterial infections or to an silvery colored hair with generalizedaccelerated phase -lymphoproliferation into the hypopigmentation of the body. Grade I clubbingmajor organs of the body4. was present. Spleen was palpable 21 cm below
the left costal margin and liver 17 cm below the decreased hemoglobin, raised ESR, neutropeniaright costal margin and lymphocytosis. Peripheral blood smear showed anisopoikilocytosis, microcytic anemia and pancytopenia. Giant granules were present in the neutrophils granulocytes and eosinophils. Fig. 3: Showing the bone marrow myeloinclusion pictureFig 1: Picture of the child Fig. 4: Showing bone marrow abnormal megakayrocytes On the basis of patient’s history, clinical findings, family history and hematological investigations, we made a provisional diagnosis of Chediak Higasi syndrome. We then opted for bone marrow aspiration and biopsy which confirmedFig. 2: Picture showing hepatosplenomegaly our diagnosis. The smear showed hyperplasticThere was cervical lymphadenopathy. Eye erythropoesis, predominantly normoblastic alongexamination revealed occulocutaneous albinism. with a few megaloblasts as well asLaboratory investigations (Table1) revealed micronormoblasts, increased monocyte
macrophage activity, vacuolation of the phase may normalize neutrophils bactericidalmonocytes and macrophages and presence of activity.abnormal granules and myeloperoxidase positiveinclusions in the neutrophils.Erythroid hyperplasia CONCLUSIONruled out any hemolytic process. Moleculartesting could not be performed due to Although this disease is rare, a high degree of awareness and early recognition of theunavailability and limited resources. On the basisof the clinical presentation, hematologic, and syndrome, can lead to the initiation of the only possible curative treatment, bone marrowhistopathological findings, a diagnosis ofaccelerated phase (lymphoma like syndrome) of transplant, before the accelerated phase supervenes.CHS was made. --------------------------------------------------------------------------The child was transfused packed cells, started on Author’s affiliationshigh dose ascorbic acid (Vitamin C) in the doseof 2000 mg per day, and stem cell Prof. Waqar Hussain, Anita Lamichhane, Mohammad Aslamtransplantation was suggested to the parents. Department of Pediatrics, Shaikh Zayed Hospital,Currently the child is under our observation, Lahore. Pakistansymptomatic treatment and follow up.Table 1:Haematological Parameters of the patient REFERENCES Patient’s Normal value value 1. Demirkiran O, Utku T, Urkmez S, Dikmen Y. Complete blood count Chediak-Higashi syndrome in the intensive Hemoglobin 6.1 gm/l 11.5-17 care unit. Pediatr Anaesth. 2004; 14(8): gm/l Total leucocyte count 2.1 x 109/l 4.0-11.0 x 685-88. 109/l 2. James WD, Berger TG, Elston DM. Neutrophils 26% 40-80% Lymphocytes 68% 20-40% Disturbances of pigmentation. In: Andrew’s Monocytes 06% 2-4% Diseases of the Skin, 10th edn. Philadelphia: Eosinophils - 0-2% WB Saunders; 2006: 853-68. Platelets counts 45 x 109 /l 150-350 x 109/l 3. Nargund AR, Madhumathi DS, Premalatha CS, Reticulocyte count 3.5 % Rao CR, Appaji L, Lakshmidevi V. Accelerated Erythrocyte sedimentation 95 mm/hr phase of Chediak Higasi syndrome mimicking rate(ESR) lymphoma--a case report. J Pediatr Hematol Oncol. 2010; 32(6): 223-26.DISCUSSION 4. Jayaranee S, Menaka N. Chediak-HigashiCHS is a very rare autosomal recessive disorder syndrome: a case report. Malays J Pathol. Junthat affects the lysosomes6.. The children exhibit 2004; 26(1): 53-57.hypopigmen-tation of the skin, hair and eyes dueto the presence of giant melanosomes which 5. Kanjanapongkul S. Chediak-Higashicause pigment dilution, possibly secondary to syndrome: report of a case with uncommonimpaired melanin transport7.A similar case was presentation and review literature. J Medreported from Lahore8. Assoc Thai. 2006; 89(4): 541-44.Ebstein-Barr virus (EBV) is implicated in the 6. Certain S, Barrat F, Pastural E, et al. Proteinaccelerated phase9. It is believed that the truncation test of LYST reveals heterogeneousinability to clear the EBV infection leads to a state mutations in patients with Chediak-Higashiof constant lymphoproliferation, as seen in the syndrome. Blood, 2000; 95(3): 979-83.phase of disease acceleration. 7. Ahluwalia J, Pattari S, Trehan A, Marwaha RK,The treatment of CHS is still controversial. Garewal G. Accelerated phase at initialParenteral vitamin C administered in the stable presentation: an uncommon occurrence in
Chediak-Higashi syndrome. Pediatr Hematol Oncol 2003; 20: 563-67.8. Massod A, Nadeem M, Aman S, Kazmi AH. Chediak-Higashi Syndrome – A Case Report. ANNALS 2008;14(3): 119-22.9. Merino F, Henle W, Ramirez-Duque P. Chronic active Epstein-Barr virus infection in patients with Chediak-Higashi syndrome. J Clin Immunol 1986; 6: 299-305.