This case report describes a rare case of Chediak Higashi syndrome (CHS) in a family. A 9-year old girl presented with pallor, hepatosplenomegaly, and pancytopenia. Blood work showed decreased hemoglobin, increased ESR, neutropenia, and lymphocytosis with abnormal granules in neutrophils and eosinophils. Bone marrow biopsy confirmed the diagnosis of CHS, showing abnormal granules and myeloperoxidase positive inclusions in neutrophils. The patient was diagnosed with the accelerated or lymphoma-like phase of CHS and started on high-dose vitamin C and a stem cell transplant was recommended.

1. CASE REPORT
Rare Case of Hemophagocytic Disorder: A Family With
Chediak Higashi Syndrome
WAQAR HUSSAIN, ANITA LAMICHHANE, MOHAMMAD ASLAM
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Pak Paed J 2012; 36(1):
ABSTRACT
Author’s affiliations
------------------------------------------- Chediak Higasi syndrome (CHS) is an autosomal recessive disorder
characterized by partial occulocutaneous albinism, increased
Correspondence to: susceptibility to infection, photophobia, a mild bleeding diathesis and a
tendency to develop a life-threatening lymphoma like syndrome. Many
Prof. Waqar Hussain similar cases of this disease with some additional features have been
Department of Pediatrics, described in the national and international journals. Pancytopenia,
Shaikh Zayed Hospital, hepatosplenomegaly, lymphohistiocytic infiltration in bone marrow and
Lahore. Pakistan the abnormal characteristic granules in leukocytes lead to the diagnosis
in the reported case.
E-mail:
gwaq_122@hotmail.com KEY WORDS: Chediak –Higashi syndrome, occulocutaneous albinism
INTRODUCTION The CHS gene was identified in 1996 and has
been mapped onto chromosome 1q42-q44 (8), a
Chediak-Higashi syndrome (CHS) was described region codes for a protein known as lysosomal
by 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 REPORT
which is characterized by incomplete
occulocutaneous hypopigmentation, photo- A nine years old girl, resident of Lahore, a product
phobia, nystagmus, large eosinophilic peroxidase of consanguineous marriage, developmentally
positive inclusion bodies in the myeloblasts and normal, a student of class V, presented with
promyelocytes of the bone marrow, neutropenia history of progressive abdominal distension for the
and an abnormal susceptibility to cutaneous and last six years and progressive pallor for the last 15
respiratory 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. No
accelerated phase, manifested by fever,
history of blood transfusion in the past. Another
lymphadenopathy, anemia, jaundice, neutro-
sibling succumbed at the age of 3 years with
penia, thrombocytopenia, and widespread
similar complaints. There was death of two other
lymphohistiocytic organ infiltrates3. This lymphoma
siblings in the family at 4 months and 8 months of
like stage is precipitated by viruses, particularly by
life respectively.
infection with Epstein-Barr virus. It is associated
with anemia, bleeding episodes, and On examination, she was extremely pale with
overwhelming infections leading to death1. erythematous rash over her face. Her growth
Morbidity results from patients succumbing to parameters were below 3rd centiles. She had
frequent bacterial infections or to an silvery colored hair with generalized
accelerated phase -lymphoproliferation into the hypopigmentation of the body. Grade I clubbing
major organs of the body4. was present. Spleen was palpable 21 cm below

2. the left costal margin and liver 17 cm below the decreased hemoglobin, raised ESR, neutropenia
right 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 picture
Fig 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 confirmed
Fig. 2: Picture showing hepatosplenomegaly
our diagnosis. The smear showed hyperplastic
There was cervical lymphadenopathy. Eye erythropoesis, predominantly normoblastic along
examination revealed occulocutaneous albinism. with a few megaloblasts as well as
Laboratory investigations (Table1) revealed micronormoblasts, increased monocyte

3. macrophage activity, vacuolation of the phase may normalize neutrophils bactericidal
monocytes and macrophages and presence of activity.
abnormal granules and myeloperoxidase positive
inclusions in the neutrophils.Erythroid hyperplasia CONCLUSION
ruled out any hemolytic process. Molecular
testing could not be performed due to Although this disease is rare, a high degree of
awareness and early recognition of the
unavailability and limited resources. On the basis
of the clinical presentation, hematologic, and syndrome, can lead to the initiation of the only
possible curative treatment, bone marrow
histopathological findings, a diagnosis of
accelerated phase (lymphoma like syndrome) of transplant, before the accelerated phase
supervenes.
CHS was made.
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The child was transfused packed cells, started on Author’s affiliations
high dose ascorbic acid (Vitamin C) in the dose
of 2000 mg per day, and stem cell Prof. Waqar Hussain, Anita Lamichhane,
Mohammad Aslam
transplantation was suggested to the parents.
Department of Pediatrics, Shaikh Zayed Hospital,
Currently the child is under our observation,
Lahore. Pakistan
symptomatic 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-Higashi
CHS is a very rare autosomal recessive disorder syndrome: a case report. Malays J Pathol. Jun
that affects the lysosomes6.. The children exhibit 2004; 26(1): 53-57.
hypopigmen-tation of the skin, hair and eyes due
to the presence of giant melanosomes which 5. Kanjanapongkul S. Chediak-Higashi
cause pigment dilution, possibly secondary to syndrome: report of a case with uncommon
impaired melanin transport7.A similar case was presentation and review literature. J Med
reported 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. Protein
accelerated phase9. It is believed that the truncation test of LYST reveals heterogeneous
inability to clear the EBV infection leads to a state mutations in patients with Chediak-Higashi
of 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 initial
Parenteral vitamin C administered in the stable presentation: an uncommon occurrence in

4. 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.