|Year : 2015 | Volume
| Issue : 1 | Page : 48-50
Griscelli syndrome type 2: A silvery hair syndrome with hemophagocytosis
Naveen Thomas1, Madhukara Jithendriya1, Anand Prakash2
1 Department of Dermatology, St. John's Medical College, Bengaluru, Karnataka, India
2 Department of Paediatrics, St. John's Medical College, Bengaluru, Karnataka, India
|Date of Web Publication||26-Jun-2015|
Department of Dermatology, St. John's Medical College, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Griscelli syndrome is a very rare autosomal recessive disorder with only about 60 cases reported in the literature. It is characterized by reduced pigmentation of the skin, silvery discoloration of the hair and immunodeficiency. Patients can have an accelerated hemophagocytic phase. The accelerated phase commonly occurs following an infection and has a high risk of mortality. Griscelli syndrome has to be distinguished from Chediak-Higashi syndrome and Elejalde disease, which can also present with silvery hair. In this case report, we discuss the child with silvery hair who presented with hemophagocytic lymphohistiocytosis following varicella infection and was diagnosed to have Griscelli syndrome.
Keywords: Chediak-Higashi syndrome, Elejalde disease, Griscelli syndrome, hemophagocytic lymphohistiocytosis, silvery hair
|How to cite this article:|
Thomas N, Jithendriya M, Prakash A. Griscelli syndrome type 2: A silvery hair syndrome with hemophagocytosis. Pigment Int 2015;2:48-50
| Introduction|| |
Griscelli syndrome, first described by Griscelli and Prunieras in 1978, is an autosomal recessive disorder, which presents with reduced pigmentation of the skin, silvery discoloration of the hair and immunodeficiency. It is a rare disorder with approximately 60 cases reported.  An important presentation of this disorder is hemophagocytic lymphohistiocytosis, a fatal condition if no appropriate treatment is given. This accelerated phase is triggered commonly by infections, mostly viral.  We present a child with Griscelli syndrome who developed hemophagocytic lymphohistiocytosis following varicella infection.
| Case Report|| |
An 1-year-old boy born of second degree consanguineous marriage presented with a history of sudden onset of high grade fever, jaundice, swelling of the abdomen, puffiness of the face and breathing difficulty since 2 weeks. The child had varicella infection 2 weeks prior to the onset of these symptoms.
On examination, patient had a toxic appearance with high grades of fever. Significant lymphadenopathy with hepatosplenomegaly was noted. There was a silvery discoloration of the hair on the scalp, eyebrows, and eyelashes [Figure 1]. Child also had a light colored skin as compared to his parents.
|Figure 1: Note the silvery discoloration of the scalp hair and the eyebrows|
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Investigation revealed bicytopenia, with hemoglobin of 5.8 gm/dl and platelets 1, 00,000/μl. Peripheral smear of the patient showed no giant phagolysosomes. Ferritin was 8162 ng/mL (normal values: 23.9-336.20 ng/mL) and the triglycerides was 279 mg/dL (normal values: <150 mg/dL), both of which were elevated. Blood culture done repeatedly showed no growth.
In view of sudden onset of high grade fever with no foci of infection with lymphadenopathy, hepatosplenomegaly and bicytopenia, along with increased ferritin and triglyceride levels, and symptoms appearing following a viral infection, a diagnosis of hemophagocytic syndrome was made. In view of the silvery discoloration of the hair, a dermatological consultation was taken. The differential diagnosis considered were
Elejalde disease was excluded as it presents with severe neurological impairment and lacks immunological abnormalities as seen in this child. Microscopic examination of the hair showed both small and large clumps of melanin arranged irregularly [Figure 2]. This finding along with the absence of giant phagolysosomes in the peripheral blood in the present clinical scenario of hemophagocytic syndrome led us to the diagnosis of Griscelli syndrome. Skin biopsy was done. The melanocytes in the basal layer showed increased pigmentation with sparse pigmentation of the surrounding keratinocytes.
|Figure 2: Microscopic examination of the hair showing irregularly arranged small and large clumps of melanin|
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The child was treated with etoposide and systemic corticosteroids. Genetic counseling was done. However, genetic analysis could not be done due to financial constraints and lack of availability of the same. There was improvement initially with fever subsiding, and the cell counts improving. However, the patient relapsed within a month.
| Discussion|| |
Griscelli syndrome is a rare inherited disorder with autosomal recessive pattern. Griscelli syndrome is further divided into three types based on the gene involved and the clinical manifestation varies accordingly. The three types are
- Griscelli syndrome type 1 (GS1)-MYO5A gene - neurological manifestations
- Griscelli syndrome type 2 (GS2)-RAB27A gene - immunological manifestations
- Griscelli syndrome type 3 (GS3)-slac2a/mlph gene - dermatological manifestations only.
The products of all the above genes form a tri-protein structure, which is required for melanin transport and deficiency of any of the gene can result in the pigmentary dilution that manifest as silver hair. 
Children with type 2 disease have immune related disorders and can develop an accelerated phase known as hemophagocytic lymphohistiocytosis. It is characterized by infiltration of the various organs by activated macrophages and lymphocytes and the patient presents with high spikes of fever with lymphadenopathy, hepatosplenomegaly and pancytopenia. These patients are found to have elevated ferritin levels and triglyceride levels.  Blood cultures are usually sterile. This accelerated phase is commonly triggered by a viral infection, although there are reports of bacterial and protozoal infections triggering the same, especially in the Indian subcontinent.  Considering the above-mentioned features, a child in this case report has type 2 Griscelli syndrome.
Griscelli syndrome has to be distinguished from other 'Silver hair syndromes' such as Chediak-Higashi syndrome and Elajalde syndrome. Both Chediak-Higashi syndrome and Griscelli syndrome can present with hemophagocytic lymphohistiocytosis.  Light microscopy examination of the hair in Griscelli syndrome shows both small and large irregular clumping of the melanin. Melanin clumps can also be seen in Chediak-Higashi syndrome. However the numbers and the size of the clumps are smaller and the clumps are arranged more regularly. Excess pigmentation of melanocytes at the basal layer of the skin is seen in Griscelli syndrome whereas Chediak-Higashi syndrome shows large melanosomes in both melanocytes and keratinocytes. Electron microscopy of the skin reveals mature melanosomes in Griscelli and large melanosomes in melanocytes and keratinocytes in the latter. Peripheral blood smear shows giant lysosomal granules in the leukocytes in patients with Chediak-Higashi syndrome.  Patients with Elejalde syndrome also present with silvery hair. However, they show associated features like excessive tanning after sun exposure and neurological impairment.  Further immunological abnormalities, including hemophagocytic lymphohistiocytosis is not seen in patients with Elejalde disease. 
| Conclusion|| |
Griscelli syndrome should be picked up at the earliest due to the risk of hemophagocytic lymphohistiocytosis and high mortality. High index of suspicion is required, and the role of a simple test like trichogram should not be underestimated.
| References|| |
Sahana M, Sacchidanand S, Hiremagalore R, Asha G. Silvery grey hair: Clue to diagnose immunodeficiency. Int J Trichology 2012;4:83-5.
Klein C, Philippe N, Le Deist F, Fraitag S, Prost C, Durandy A, et al.
Partial albinism with immunodeficiency (Griscelli syndrome). J Pediatr 1994;125:886-95.
Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, editors. Fitzpatrick's Dermatology in General Medicine. 7 th
ed.. New York: McGraw-Hill; 2008.
Rajagopala S, Singh N. Diagnosing and treating hemophagocytic lymphohistiocytosis in the tropics: Systematic review from the Indian subcontinent. Acta Med Acad 2012;41:161-74.
Dinakar C, Lewin S, Kumar KR, Harshad SR. Partial albinism, immunodeficiency, hypergammaglobulinemia and Dandy-Walker cyst - A Griscelli syndrome variant. Indian Pediatr 2003;40:1005-8.
Reddy RR, Babu BM, Venkateshwaramma B, Hymavathi Ch. Silvery hair syndrome in two cousins: Chediak-Higashi syndrome vs Griscelli syndrome, with rare associations. Int J Trichology 2011;3:107-11.
Inamadar AC, Palit A. Silvery hair with bronze-tan in a child: A case of Elejalde disease. Indian J Dermatol Venereol Leprol 2007;73:417-9.
Duran-McKinster C, Rodriguez-Jurado R, Ridaura C, de la Luz Orozco-Covarrubias M, Tamayo L, Ruiz-Maldonando R. Elejalde syndrome - A melanolysosomal neurocutaneous syndrome: Clinical and morphological findings in 7 patients. Arch Dermatol 1999;135:182-6.
[Figure 1], [Figure 2]