CASE REPORT

Chediak-Higashi Syndrome in Accelerated Phase: A Rare CaseReport with Review of Literature

Shivani Sood • Biswajit Biswas • Vijay Kaushal •

Tanish Mandal

Received: 10 August 2013 / Accepted: 24 December 2013

� Indian Society of Haematology & Transfusion Medicine 2014

Introduction

Chediak-Higashi syndrome (CHS) is an extremely rare

autosomal recessive primary immunodeficiency disease.

The first case was reported in 1943. Since its first

description, around 200 cases have been reported world-

wide [1] and about 10 cases have been reported from India

[2]. CHS is characterized by partial ocular and cutaneous

albinism, increased susceptibility to pyogenic infections,

the presence of large lysosomal-like organelles in most

granule-containing cells and a bleeding tendency. Other

clinical features include silvery hair, photophobia, hori-

zontal and rotatory nystagmus and hepatosplenomegaly.

Definitive diagnosis can only be made when the pathog-

nomic abnormal large granules are noted in the leucocytes

and other granule-containing cells [3].

Due to the rarity of the condition and the characteristic

clinical and hematological findings, we are hereby report-

ing a case of Chediak-Higashi syndrome.

Case Report

A 2 years old male child presented with fever and pain

abdomen for 9 days. There was history of loose watery

stools for 2 days, increased frequency of micturition and

1 kg weight loss over last 9 days. Past history revealed

similar episodes occurring almost every one to 2 months

and each episode lasting 4–5 days ever since birth and

history of post vaccine abscess right thigh at 8 months of

age. There were silver grey hair and white spots on face

since 2 months of age increasing to present stage by

5 months. The child weighed 9,700 g (3rd centile) and

length of 84 cm (between 10th and 25th centile). On

examination, there were silver grey hair (Fig. 1), patchy

alopecia, hypopigmentation in peri-oral region, cheek, back

and gluteal region, abdomen, forearm, hands, feet includ-

ing palms and sole (Figs. 2, 3), bilateral cataract, brachy-

dactyly, erythematous papules over axilla and foot

associated with itching along with pallor and hepato-

splenomegaly. Investigations revealed pancytopenia with

febrile neutropenia. Routine urine and CSF examination

were normal. Blood cultures and urine cultures were neg-

ative. Serology for TORCH group of infections, dengue

and typhoid were negative. Abdominal ultrasound revealed

hepatosplenomegaly. Chest X-ray revealed cardiomegaly.

Peripheral smear examination revealed mild anisocytosis,

platelets were reduced and differential leucocyte count

revealed 13 % neutrophils, 85 % lymphocytes and 2 %

monocytes. Neutrophils revealed inclusion like structures

and coarse granules (Fig. 4). Bone marrow examination

revealed cellular preparations with M:E ratio 1:4 (erythroid

hyperplasia). Erythropoeisis was megaloblastic with fea-

tures of dyserythropoeisis. The most characteristic feature

was presence of one to two to numerous intracytoplasmic

eosinophilic coarse granules and inclusion-like granules in

S. Sood (&) � B. Biswas � V. Kaushal � T. Mandal

Department of Pathology, IGMC Shimla, 73/3, Ram Bazaar,

Shimla, HP 171001, India

e-mail: shivanisood343@rediff.com

B. Biswas

e-mail: drbiswajit2031@gmail.com

V. Kaushal

e-mail: drkaushalvijay@gmail.com

T. Mandal

e-mail: tanishmandal@gmail.com

123

Indian J Hematol Blood Transfus

DOI 10.1007/s12288-013-0325-5

the granulocytic cells, lymphocytes and monocytes

(Figs. 5, 6). The granules were positive for myeloperoxi-

dase (Fig. 7). Histiocytes revealed phagocytosis of hema-

topoietic cells. Thus a diagnosis of Chediak-Higashi

syndrome in accelerated phase was made. Unfortunately,

the child died within 1 month of diagnosis.

Discussion

CHS was first described by Bequez-cesar in 1943. Later

Chediak, a Cuban hematologist and Higashi, a Japanese

Fig. 1 Silver grey hair on scalp and eyebrows

Fig. 2 Hypopigmented lesions on back and gluteal region

Fig. 3 Hypopigmented lesions on chest, abdomen and forearm

Fig. 4 PBF: eosinophilic coarse granules in neutrophils

Fig. 5 BMA: inclusion like granules in myeloid precursors

Indian J Hematol Blood Transfus

123

paediatrician described a series of cases in 1952 and 1954

respectively. In 1955 Sato coined the term Chediak-Hig-

ashi syndrome [2]. Mean age of presentation is 2 years and

male to female ratio is 1:1 [4].

The basic pathology in CHS is defect in the lysosomal

trafficking regulator (LYST) gene on chromosome 1, whose

gene product regulates intracellular protein trafficking to

and from the lysosome. Impaired function of this protein

disrupts the size, structure and function of lysosomes in the

body, resulting in the accumulation of large intracellular

vesicles within:

1. Granulocytes resulting in impaired phagolysosome fusion,

thus increasing susceptibility to bacterial infections.

2. Platelets resulting in coagulopathies, thus easy bruis-

ability and bleeding diathesis.

3. Melanocytes resulting in faulty intracellular transporta-

tion of melanin and the presence of giant melanosomes

in the melanocytes leading to partial oculo-cutaneous

albinism, fair skin and silver hair.

They may also present with sensory and/or motor neu-

rological disorders or nystagmus [1]. An additional finding

that has not been reported in any previous case reports but

seen in our case is bilateral cataract.

Uyama et al. suggested two distinct clinical presenta-

tions: (1) the more commonly recognized childhood form

with a typical history of recurrent infections leading to

early death or an accelerated phase and (2) the rare adult

type in which neurological defects resembling parkinson-

ism, dementia or spinocerebellar degeneration and

peripheral neuropathy dominate with a lack of increased

susceptibility to infections [5].

Roy et al. [6] in 2011 studied the clinicohematological

profile of 5 cases of CHS and concluded that the diagnostic

hallmark of CHS is the occurrence of giant inclusion

bodies (granules) in the peripheral leukocyte and their bone

marrow precursors.

The condition has to be differentiated from various

clinical entities. The clinical features of Griscelli syndrome

are similar to Chediak-Higashi syndrome but the presence

of myeloperoxidase positive inclusions in the bone marrow

helped to delineate the condition. Hermansky-Pudlak syn-

drome is a platelet storage deficiency disorder manifesting

as easy bruising and a bleeding tendency associated with

oculo-cutaneous albinism and pulmonary fibrosis but there

is no defect in circulating lymphocytes or neutrophils

which differentiates this disease from the condition of our

patient. In patients of Prader Willi’s syndrome and Ang-

elman’s syndrome, there is hypopigmentation but usually

no typical ocular features of albinism. In Prader Willi’s

syndrome, the characteristic features are neonatal hypoto-

nia, hyperphagia, hypogonadism and mental retardation

while in Angelman’s syndrome, there is severe mental

retardation, microcephaly, neonatal hypotonia, ataxic

movements and inappropriate laughter. Waardenburg syn-

drome is a neural crest disorder. Pie-baldism, with a white

forelock hypopigmentation, congenital deafness, synophrys

and dystopia canthorum (broad nasal root) are the distinct

clinical features. Myeloblasts also fail to survive. In lazy

leukocyte syndrome, pus is absent in cutaneous lesions and

neutrophilia is a constant finding [7]. Acute and chronic

myeloid leukemia may show giant granules resembling

those seen in CHS, also referred to as pseudo-Chediak-

Higashi anomaly [2].

About 50–85 % of the patients with CHS enter into an

accelerated phase manifested by fever, jaundice, anemia,

neutropenia, thrombocytopenia, hepatosplenomegaly,

lymphadenopathy and widespread lymphohistiocytic infil-

tration of various organs with hemophagocytosis leading to

pancytopenia and bleeding disorder secondary to low

Fig. 6 BMA: eosinophilic inclusion like granules

Fig. 7 BMA: myeloperoxidase positive granules

Indian J Hematol Blood Transfus

123

platelets and fibrinogen levels. This child had five out of

seven clinical features and evidence of hemophagocytosis

on bone marrow examination thus concluding that the child

had progressed to the accelerated phase of Chediak-Hig-

ashi syndrome and died within 1 month of diagnosis.

Bone marrow transplant (BMT) is the treatment of

choice before the accelerated phase. Without BMT, chil-

dren of CHS die before 10 years of age [4]. Familial

consanguinity has been described in 50 % of CHS cases in

the literature, yet there have been many reports of CHS in

children of unrelated parents. Prenatal diagnosis is a

technically difficult process, but can be made by measuring

acid phosphatase-positive lysosomes from cultures of

amniotic fluid cells, chorionic villous cells, or leukocytes

isolated from foetal blood [1].

To conclude, CHS is an extremely rare condition with a

poor prognosis. Characteristic clinical features and typical

blood and bone marrow findings are essential for early

diagnosis and treatment.

References

1. Saeed N, Al-Saed K, Shome D, Jamsheer H (2012) A child with

Chediak-Higashi and trisomy 21 syndromes. Royal Coll Surg

Ireland Stud Med J 5:47–49

2. Rani H, Kanabur D (2012) Accelerated phase of Chediak-Higashi

syndrome—a case report with review of literature. J Pediatr Sci

4:e167

3. Jayaranee S, Menaka N (2004) Chediak-Higashi syndrome: a case

report. Malaysian J Pathol 26:53–57

4. Farhoudi A, Chavoshzadeh Z, Pourpak Z, Izadyar M, Gharagoslou

M, Movahedi M et al (2003) Report of six cases of Chediak-

Higashi syndrome with regard to clinical and laboratory findings.

Iran J Allergy Asthma Immunol 2:189–192

5. Pujani M, Agarwal K, Bansal S, Ahmad I, Puri V, Verma D et al

(2011) Chediak-higashi syndrome- a report of two cases with

unusual hyperpigmentation of the face. Turkish J Pathol 27:246–248

6. Roy A, Kar R, Basu D, Srivani S, Badhe M (2011) Clinico-

hematologic profile of Chediak-Higashi syndrome: experience

from a tertiary care centre in south India. Indian J Pathol Microbiol

54:547–551

7. Masood A, Nadeem M, Aman S, Kazmi A (2008) Chediak-Higashi

syndrome—a case report. Annals 14:119–122

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