Official Journal of the European Paediatric Neurology Society

Case study

Bilateral basal ganglia involvement in a patient withGriscelli syndrome

Mahmoud Reza Ashrafi�, Meysam Mohseni, Shahrooz Yazdani, Houman Alizadeh,Asghar Ramyar, Asghar Aghamohammadi, Mina Izadyar, Fatemeh Mahjoub,Javad Ahmadian Heris

Children hospital Medical Center, Tehran University of Medical Sciences, Pediatric Neurology, Tehran 1419733151, Iran

a r t i c l e i n f o

Article history:

Received 12 June 2006

Received in revised form

20 July 2006

Accepted 30 July 2006

Keywords:

Griscelli Syndrome

Partial albinism

Neurological involvement

A B S T R A C T

We report a 6-year-old Iranian boy with silvery-gray hair, eyelashes and the eyebrows who

was admitted because of seizures and subsequent stupor. He had previous history of acute

hemiparesis at 1 year of age and hepatitis-like syndrome 3 months ago. Microscopic

examination of the patient’s hair shaft revealed different sized clumps of melanin seen in

the center of the shafts. Bone marrow aspiration revealed erythroid hyperplasia and

erythrophagocytic cells. Bilateral frontal cortical and subcortical high signal lesions, dirty

white matter, high signal areas in the upper pons and in both caudates and lentiform

nuclei in T2 WI were the brain MRI findings of the patient. He died in the accelerated phase

of Griscelli Syndrome (GS) type 2. To our knowledge we report the first case of GS from Iran.

& 2006 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

1. Introduction

In 1978, Griscelli and colleagues initially described a disorder

resembling the Chediak-Higashi syndrome (CHS) in two

children with partial albinism, frequent infections, acute

episodes of fever, neutropenia and thrombocytopenia1

and since then more than 60 patients with Griscelli Syndrome

(GS) have been reported in the literature. GS is a rare

recessively inherited hypopigmentation disorder that results

in pigmentary dilution of the skin and the hair, the presence

of large clumps of pigment in hair shafts, variable cellular

immune deficiency and occurrence of uncontrolled lympho-

cyte and macrophage activation with consequent neurological

deficits.1,2

Two closely linked genes (RAB27A and MYO5A) on chromo-

some 15q21 region have been found to be responsible for the

GS.3 According to mutation analysis three subtypes have been

described.

GS type 1 (GS1) represents hypomelanosis with a primary

neurologic deficit and without immunologic impairment

which is caused by mutations in the MYO5A gene.3,4 Patients

exhibit severe developmental delay and mental retardation

occurring early in life.

GS type 2 (GS2) is characterized by partial albinism,

immunodeficiency and hemophagocytic syndrome (HS)

which is caused by mutation in RAB27A gene.3,4

HS or accelerated phase is characterized by lymphoid organ

and extranodal infiltration including the brain by polyclonal

activated T cells and macrophages. HS usually results in

death unless the child receives a bone marrow transplant.

GS type 3 (GS3) is characterized by hypomelanosis without

immunologic or neurologic manifestations which is due to

mutation of melanophilin or MYO5A genes.

In the present study we report a 6-year-old Iranian boy with

GS. We describe the clinical and paraclinical manifestations

with emphasis on neurological and neuroimaging findings.

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1090-3798/$ - see front matter & 2006 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.doi:10.1016/j.ejpn.2006.07.005

�Corresponding author. Tel.: +98 2166935848; fax: +98 2166930024.E-mail address: mr_ashrafi@yahoo.com (M.R. Ashrafi).

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2. Case presentation

A 6-year-old boy was referred to Children’s Medical Center of

Tehran University of Medical Sciences because of decreased level

of consciousness, seizure disorder and fever.

During the previous 6 weeks, the patient became febrile

with three episodes of tonic-clonic seizures. Depression of

consciousness manifested as the third episode occurred.

He was the third child of consanguineous parents and was

delivered at term during a caesarian section delivery with

unremarkable birth history. The first child who was a girl also

had silvery-grayish hair and was admitted to a local hospital

with the complaint of jaundice at 3 years of age. She died

after 3 days of admission with unknown etiology. The second

child is a 10-year-old healthy boy with dark brown hair.

The third child, the patient, had no problem through the

first year of life with normal development. He walked

independently at 1 year of age. At 13 months of age he was

first admitted due to acute right-sided hemiplegia and several

episodes of fits. Brain Computed Tomography (CT) scan was

in favor of stroke. Since the first admission, he faced some

neurodevelopmental delays. With the help of frequent

occupational and speech therapies he walked at 3.5 years of

age and spoke at 4 years of age. Except frequent upper

respiratory tract infections, he had no problem until 3 months

ago when he was admitted in a local hospital with the

complaint of jaundice. Hepatomegaly, both direct and indirect

hyperbilirubinemia, mild elevation of liver enzymes and no

evidence of viral hepatitis were the prominent physical

examination and laboratory findings. The patient gradually

improved and discharged with no definite diagnosis.

On the last admission he was responsive only to painful

stimuli, had fever and 3 left-sided cervical lymphadenopa-

thies. Bilateral hyperreflexia, babinski and ankle clonus were

seen. The hair, eyelashes and the eyebrows were silvery-gray

but his skin was slightly bronzed.

Hematologic and biochemistric findings included: hemoglo-

bin (Hgb) ¼ 11.9 gr/dl, white blood cell count (WBC) ¼ 3100/ml,

platelet count (PLT) ¼ 60,000/ml, Prothrombin Time (PT) ¼ 15.5 s,

Partial Thromboplastin Time (PTT) ¼ 41 s, Bleeding Time

(BT) ¼ 2 min, triglyceride ¼ 345 mg/dl and peripheral blood

smear showed no giant cytoplasmic granules in the leuko-

cytes. Bone marrow aspiration revealed erythroid hyperplasia

and some erythrophagocytic cells. The cerebrospinal fluid (CSF)

findings were normal. Ultrasound showed mild splenomegaly.

Delayed-type hypersensitivity skin tests for Purified protein

derivative (PPD) and Candida were negative. Immunopheno-

typing revealed low percentages of CD4+ T-cells and high

percentages of CD8+ T-cells. Serum immunoglobulin levels

were within normal limits.

Electroencephalogram (EEG) showed high-voltage slow waves

and spike–wave complexes.

Microscopic examination of the patient’s hair shaft re-

vealed different sized clumps of melanin seen in the center of

the shafts.

T2 WI of the brain MRI reveals frontal cortical and

subcortical ill-defined high signal lesions, dirty white matter

of both centrum semiovale and periventricular areas, high

signal areas in the upper pons, quadrigeminal plate, bilateral

caudates and lentiform nuclei, interhemispheric tract, right

aspect of the splenium of the corpus callosum and subcortical

left parietal region (Figs. 1A, B, and C).

Within 7 days, stupor changed to coma and spleen became

palpable 4 cm below the costal margin. Hemoglobin de-

creased to 8.6 g/dl and platelet count to 6000 /ml within a

week after admission. Bleeding occurred from catheter sites

on the 10th day of admission.

Despite intensive supportive care, the patient’s clinical

condition worsened and 2 days later cardiopulmonary arrest

happened and the patient expired on the 12th day of

admission. His family refused autopsy.

Based on the family history and some physical features

particularly silvery-gray hair and a hepatits-like syndrome,

we suggested the diagnosis of GS and it was confirmed by

light microscopic examination of hair, bone marrow aspira-

tion analysis and some compatible laboratory data.

3. Discussion

We report an Iranian boy with the diagnosis of GS with some

new neuroradiologic findings who is the first reported case of GS

from Iran.

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Fig. 1 – Brain T2 WI frontal cortical and subcortical high signal lesions and dirty white matter (a), bilateral caudate and

lentiform nucleoli high signal areas (b), high signal area in upper pons (c).

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The single most consistent expression of partial albinism in

GS is silvery-gray hair, eyebrows and eyelashes, diffuse skin

hypopigmentation and in few reported cases hyperpigmenta-

tion in sun-exposed areas of the skin.

In GS hair shafts contain atypical pattern of uneven

accumulation of large pigment granules in contrast to the

homogenous distribution of small pigment granules in

normal hair and regular, small aggregates of melanin in

CHS.1–3 The skin of the present patient was slightly dark and

his dermatologic findings were limited to pigmentary ab-

normalities of the hair, eyelashes and eyebrows. Microscopic

examination of the patient’s hair revealed irregular large

aggregations of melanin pigment.

Giant cytoplasmic granules in leukocytes which are pathog-

nomonic for CHS were not seen.

A diagnosis of GS was made by the silvery-gray hair and the

characteristic microscopic changes of the hair in association

with the clinical and paraclinical features of accelerated

phase including prolonged fever, jaundice, splenomegaly,

lymphadenopathy, pancytopenia, hypertriglyceridemia and

hemophagocytes in the bone marrow.

The spectrum of neurological involvement in GS may range

from an early onset of severe neurological disorder to the

form that accompanies the accelerated phase.

In GS1, severe neurologic symptoms are noticeable at birth

without any sign of an accelerated phase or immunologic

impairment. Neurologic disorders are stable and never

regresses with time and consist of hypotonia, absence of

coordinated voluntary movements, encephalopathy, hemi-

paresis, peripheral facial palsy, spasticity, seizures and

psychomotor retardation. Congenital cerebellar atrophy is

the main neuroimaging finding in GS1.

Patients with GS2 have neurologic problems related to HS

and a lymphohistiocytic infiltration of the CNS. Neurological

manifestations can be the first sign of an accelerated phase.

The symptoms include hyperreflexia, hypertonia, seizures,

increased intracranial pressure, regression of developmental

milestones, nystagmus, ataxia and fatal degeneration. Psy-

chomotor development is normal primarily and then re-

gresses in HS Encephalopathy, long tract involvement and

previous episode of hemiparesis due to ischemic stroke were

the main neurologic findings of the patient. The neurologic

manifestations of the patient were due to HS and compatible

with GS2. Cerebellar hypodense areas, ventricular dilatation,

generalized white matter changes, periventricular and basal

ganglia calcifications and hyperdense areas compatible

with inflammatory changes are the main neuroimaging

findings in GS2.5 As noted above, our patient had a previous

isolated episode of neurologic symptoms in the early child-

hood which we suggest as an early episode of HS. Since we do

not have access to the patient’s early-childhood-medical

documents, it is not apparent to us that this episode was

due to HS or not.

Bilateral basal ganglia involvement and old necrotic area in

brainstem were the special findings in his brain MRI that in

our knowledge are not reported till now.

GS must be considered in a child with any neurologic

disorders associated with partial albinism.

R E F E R E N C E S

1. Griscelli C, Durandy A, Guy-Grand D, et al. A syndromeassociating partial albinism and immunodeficiency. Am J Med1978;65:691–702.

2. Klein C, Philippe N, Le Deist F, et al. Partial albinism withimmunodeficiency (Griscelli syndrome). J Pediatr1994;125:886–95.

3. Menasche G, Fischer A, de Saint Basile G. Griscelli syndrometypes 1 & 2. Am J Hum Genet 2002;71:1237–8.

4. Mancini AJ, Chan LS, Paller AS. Partial albinism with immuno-deficiency: Griscelli syndrome: report of a case and review ofthe literature. J Am Acad Dermatol 1998;38:295–300.

5. Hurvitz H, Gillis R, Klaus S. A kindred with Griscelli disease:spectrum of neurological involvement. Eur J Pediatr 1993;152:4.

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