chediak higashi syndrome

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CASE REPORT Rare Case of Hemophagocytic Disorder: A Family With Chediak Higashi Syndrome WAQAR HUSSAIN, ANITA LAMICHHANE, MOHAMMAD ASLAM ------------------------------------------------------------------ Pak Paed J 2012; 36(1): Author’s affiliations ------------------------- ------------------ Correspondence to: Prof. Waqar Hussain Department of Pediatrics, Shaikh Zayed Hospital, Lahore. Pakistan E-mail: [email protected] ABSTRACT Chediak Higasi syndrome (CHS) is an autosomal recessive disorder characterized by partial occulocutaneous albinism, increased susceptibility to infection, photophobia, a mild bleeding diathesis and a tendency to develop a life- threatening lymphoma like syndrome. Many similar cases of this disease with some additional features have been described in the national and international journals. Pancytopenia, hepatosplenomegaly, lymphohistiocytic infiltration in bone marrow and the abnormal characteristic granules in leukocytes lead to the diagnosis in the reported case. KEY WORDS: Chediak –Higashi syndrome, occulocutaneous albinism INTRODUCTION Chediak-Higashi syndrome (CHS) was described by Beguez Cesar in 1943, Steinbrinck in 1948, Chediak in 1952, and Higashi in 1954 1 . Chediak-Higashi syndrome is a rare lysosomal disorder which is characterized by incomplete occulocutaneous hypopigmentation, photo- phobia, nystagmus, large eosinophilic peroxidase positive inclusion bodies in the myeloblasts and promyelocytes of the bone marrow, neutropenia and an abnormal susceptibility to cutaneous and respiratory infections 2 . About 50% to 85% of patients eventually enter an accelerated phase, manifested by fever, lymphadenopathy, anemia, jaundice, neutro-penia, thrombocytopenia, and widespread lymphohistiocytic organ infiltrates 3 . This lymphoma like stage is precipitated by viruses, particularly by infection with Epstein-Barr virus. It is associated with anemia, bleeding episodes, and overwhelming infections leading to death 1 . Morbidity results from patients succumbing to frequent bacterial infections or to an accelerated phase -lymphoproliferation into the major organs of the body 4 . The CHS gene was identified in 1996 and has been mapped onto chromosome 1q42-q44 (8), a region codes for a protein known as lysosomal trafficking regulator 5 .

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Page 1: Chediak higashi syndrome

CASE REPORT

Rare Case of Hemophagocytic Disorder: A Family With Chediak Higashi SyndromeWAQAR HUSSAIN, ANITA LAMICHHANE, MOHAMMAD ASLAM

------------------------------------------------------------------Pak Paed J 2012; 36(1):

Author’s affiliations

-------------------------------------------

Correspondence to:

Prof. Waqar HussainDepartment of Pediatrics,Shaikh Zayed Hospital,Lahore. Pakistan

E-mail: [email protected]

ABSTRACT

Chediak Higasi syndrome (CHS) is an autosomal recessive disorder characterized by partial occulocutaneous albinism, increased susceptibility to infection, photophobia, a mild bleeding diathesis and a tendency to develop a life-threatening lymphoma like syndrome. Many similar cases of this disease with some additional features have been described in the national and international journals. Pancytopenia, hepatosplenomegaly, lymphohistiocytic infiltration in bone marrow and the abnormal characteristic granules in leukocytes lead to the diagnosis in the reported case.

KEY WORDS: Chediak –Higashi syndrome, occulocutaneous albinism

INTRODUCTION

Chediak-Higashi syndrome (CHS) was described by Beguez Cesar in 1943, Steinbrinck in 1948, Chediak in 1952, and Higashi in 19541. Chediak-Higashi syndrome is a rare lysosomal disorder which is characterized by incomplete occulocutaneous hypopigmentation, photo-phobia, nystagmus, large eosinophilic peroxidase positive inclusion bodies in the myeloblasts and promyelocytes of the bone marrow, neutropenia and an abnormal susceptibility to cutaneous and respiratory infections2.

About 50% to 85% of patients eventually enter an accelerated phase, manifested by fever, lymphadenopathy, anemia, jaundice, neutro-penia, thrombocytopenia, and widespread lymphohistiocytic organ infiltrates3. This lymphoma like stage is precipitated by viruses, particularly by infection with Epstein-Barr virus. It is associated with anemia, bleeding episodes, and overwhelming infections leading to death1. Morbidity results from patients succumbing to frequent bacterial infections or to an accelerated phase -lymphoproliferation into the major organs of the body4.

The CHS gene was identified in 1996 and has been mapped onto chromosome 1q42-q44 (8), a region codes for a protein known as lysosomal trafficking regulator5.

CASE REPORT

A nine years old girl, resident of Lahore, a product of consanguineous marriage, developmentally normal, a student of class V, presented with history of progressive abdominal distension for the last six years and progressive pallor for the last 15 days. The child had some febrile illness two weeks back. There was no history of petechiae, bruises, recurrent chest and skin infections, or boils. No history of blood transfusion in the past. Another sibling succumbed at the age of 3 years with similar complaints. There was death of two other siblings in the family at 4 months and 8 months of life respectively.

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On examination, she was extremely pale with erythematous rash over her face. Her growth parameters were below 3rd centiles. She had silvery colored hair with generalized hypopigmentation of the body. Grade I clubbing was present. Spleen was palpable 21 cm below the left costal margin and liver 17 cm below the right costal margin

Fig 1: Picture of the child

Fig. 2: Picture showing hepatosplenomegaly

There was cervical lymphadenopathy. Eye examination revealed occulocutaneous albinism. Laboratory investigations (Table1) revealed decreased hemoglobin, raised ESR, neutropenia 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 picture

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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 confirmed our diagnosis. The smear showed hyperplastic erythropoesis, predominantly normoblastic along with a few megaloblasts as well as micronormoblasts, increased monocyte macrophage activity, vacuolation of the monocytes and macrophages and presence of abnormal granules and myeloperoxidase positive inclusions in the neutrophils.Erythroid hyperplasia ruled out any hemolytic process. Molecular testing could not be performed due to unavailability and limited resources. On the basis of the clinical presentation, hematologic, and histopathological findings, a diagnosis of accelerated phase (lymphoma like syndrome) of CHS was made.

The child was transfused packed cells, started on high dose ascorbic acid (Vitamin C) in the dose of 2000 mg per day, and stem cell transplantation was suggested to the parents. Currently the child is under our observation, symptomatic treatment and follow up.

Table 1:Haematological Parameters of the patient

Patient’s value

Normal value

Complete blood countHemoglobin 6.1 gm/l 11.5-17

gm/lTotal leucocyte count 2.1 x 109/l 4.0-11.0

x 109/lNeutrophils 26% 40-80%Lymphocytes 68% 20-40%Monocytes 06% 2-4%Eosinophils - 0-2%Platelets counts 45 x 109 /l 150-350

x 109/lReticulocyte count 3.5 %Erythrocyte sedimentation rate(ESR)

95 mm/hr

DISCUSSION

CHS is a very rare autosomal recessive disorder that affects the lysosomes6.. The children exhibit hypopigmen-tation of the skin, hair and eyes due to the presence of giant melanosomes which cause pigment dilution, possibly secondary to impaired melanin transport7.A similar case was reported from Lahore8.

Ebstein-Barr virus (EBV) is implicated in the accelerated phase9. It is believed that the inability to clear the EBV infection leads to a state of constant lymphoproliferation, as seen in the phase of disease acceleration.

The treatment of CHS is still controversial. Parenteral vitamin C administered in the stable phase may normalize neutrophils bactericidal activity.

CONCLUSION

Although this disease is rare, a high degree of awareness and early recognition of the syndrome, can lead to the initiation of the only possible curative treatment, bone marrow transplant, before the accelerated phase supervenes.--------------------------------------------------------------------------Author’s affiliations

Prof. Waqar Hussain, Anita Lamichhane, Mohammad AslamDepartment of Pediatrics, Shaikh Zayed Hospital, Lahore. Pakistan

REFERENCES

1. Demirkiran O, Utku T, Urkmez S, Dikmen Y. Chediak-Higashi syndrome in the intensive care unit. Pediatr Anaesth. 2004; 14(8): 685-88.

2. James WD, Berger TG, Elston DM. Disturbances of pigmentation. In:

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Andrew’s Diseases of the Skin, 10th edn. Philadelphia: WB Saunders; 2006: 853-68.

3. Nargund AR, Madhumathi DS, Premalatha CS, Rao CR, Appaji L, Lakshmidevi V. Accelerated phase of Chediak Higasi syndrome mimicking lymphoma--a case report. J Pediatr Hematol Oncol. 2010; 32(6): 223-26.

4. Jayaranee S, Menaka N. Chediak-Higashi syndrome: a case report. Malays J Pathol. Jun 2004; 26(1): 53-57.

5. Kanjanapongkul S. Chediak-Higashi syndrome: report of a case with uncommon presentation and review literature. J Med Assoc Thai. 2006; 89(4): 541-44.

6. Certain S, Barrat F, Pastural E, et al. Protein truncation test of LYST reveals heterogeneous mutations in patients with Chediak-Higashi syndrome. Blood, 2000; 95(3): 979-83.

7. Ahluwalia J, Pattari S, Trehan A, Marwaha RK, Garewal G. Accelerated phase at initial 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.