Year : 2006 | Volume
: 51 | Issue : 4 | Page : 269--271
T Sathish Kumar, Sam Ebenazar, Prabhakar D Moses
Department of Child Health Unit III, Christian Medical College, Vellore, India
Prabhakar D Moses
Department of Child Health Unit III, Christian Medical College, Vellore - 632 004, Tamil Nadu
Partial albinism with immunodeficiency is a rare and fatal immunologic disorder characterized by pigmentary dilution and variable cellular immunodeficiency. It was initially described in 1978. Primary abnormalities included silvery grayish sheen to the hair, large pigment agglomerations in hair shafts and an abundance of mature melanosomes in melanocytes, with reduced pigmentation of adjacent keratinocytes. We describe a child with Griscelli syndrome who presented with hepatitis, pancytopenia and silvery hair. The diagnosis was confirmed by microscopic skin and hair examination.
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Kumar T S, Ebenazar S, Moses PD. Griscelli syndrome.Indian J Dermatol 2006;51:269-271
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Kumar T S, Ebenazar S, Moses PD. Griscelli syndrome. Indian J Dermatol [serial online] 2006 [cited 2021 Dec 4 ];51:269-271
Available from: https://www.e-ijd.org/text.asp?2006/51/4/269/30292
Griscelli syndrome is a rare autosomal recessive disease characterized by pigmentary dilution of skin and hair, variable cellular immunodeficiency and an acute phase of uncontrolled T lymphocyte and macrophage activation leading to fatal hemophagocytic syndrome. It was first described by Griscelli in 1978, and since then only around 60 cases have been reported, mostly from the Turkish and Mediterranean population. Only few cases are reported from India. We present a child with classic clinical features and confirmatory findings of clumped melanosomes on microscopy of hair shaft.
A 4-year-old male child presented with fever, jaundice and abdominal distension for two weeks and bleeding from lips for four days. He was first born to nonconsanguineous parents by normal vaginal delivery at term. His development was normal and he was adequately immunized for age.
At admission, his vitals were stable. His height was 93 cms, weight was 11 kg and head circumference was 42 cms. He had silvery grey sheen hair [Figure 1]. He had pallor, icterus with bilateral pitting pedal edema. He had bleeding from lips. Abdominal examination revealed firm hepatomegaly of 10 cms and splenomegaly of 8 cms. Respiratory system examination revealed decreased air entry on both sides with dullness to percussion in left infraaxillary and interscapular areas. CVS and CNS examinations were within normal limits.
Investigations revealed hemoglobin of 7 gm/dl, total leukocyte count of 6200/cu.mm with differential count of L64%, N24%, Band forms 10% and myelocytes 2%, platelets 4000 cu.mm. Blood picture did not show azurophil granules. Prothrombin time and activated partial thromboplastin time were prolonged. Malarial parasite was negative. Serum electrolytes, calcium and creatinine were normal. Liver function test revealed total bilirubin of 2.8 mg%, direct bilirubin of 2.4 mg%, total protein of 3.2 gm%, albumin of 1.4 gm%, SGOT of 285 U/L, SGPT 117 U/I and alkaline phosphatase 341 U/L. Lipid profile revealed cholesterol 170 mg%, triglycerides 316 mg%, high-density lipoprotein cholesterol 48 mg% and low-density lipoprotein cholesterol 59 mg%. Serum ceruloplasmin and 24h urinary copper were within normal limits. Serum immunoglobulin was IgG 669 mg%, IgA 112 mg% and IgM 187 mg%. Viral markers for hepatitis (HAV and HBV) were negative. HIV ELISA, Dengue IgG and IgM were negative. Bone marrow examination and culture were normal. ESR was normal and anti-nuclear antibody was negative. Chest radiograph revealed bilateral pneumonitis. His ultrasonography abdomen revealed hepatosplenomegaly.
His hair examination revealed irregular pigment clumps in hair shaft [Figure 2]. His skin biopsy revealed clumped pigment deposition in the basal epithelial layer and pigment in the keratinocytes. With clinical and laboratory findings he was diagnosed as Griscelli syndrome.
He was treated with IV fluids, oxygen, antibiotics, blood and blood products. During hospital stay he developed upper GI bleed and endoscopy revealed erosive antral gastritis. He improved with the above measures and was discharged. Allograft bone marrow transplant was deferred in view of no other sibling.
In 1978 Griscelli et al . described two patients with partial albinism of hair and skin, frequent pyogenic infections and acute episodes of fever, hepatosplenomegaly, neutropenia and thrombocytopenia. It is clinically characterized by accelerated phases triggered by viral or bacterial infections. Characteristic laboratory features included pancytopenia, hypofibrinogenemia, hypertriglyceridemia, hypoproteinemia. Immunologic abnormalities most often include impaired natural killer cell activity, absent delayed-type hypersensitivity and impaired responses to mitogens. Impaired helper T cell function and hypogammaglobulinemia have also been described. Microscopic examination of hair shafts reveals uneven clusters of aggregated melanin pigments, accumulated mainly in the medullary area of the shaft. Histopathological examination of skin biopsy shows hyper-pigmented oval melanocytes with poorly pigmented adjacent keratinocytes. Electron microscopic evaluation of skin specimens shows epidermal melanocytes filled with numerous stage IV melanosomes arranged in a perinuclear distribution, without giant melanosomes. Neurologic involvement is prominent in many patients with Griscelli syndrome., Clinical manifestations include intracranial hypertension, cerebellar signs, bulbar poliomyelitis, encephalopathy, hemiparesis, peripheral facial palsy, hypotonia seizures, and psychomotor retardation.
The differential diagnosis of the disease in the patient presenting with silvery hair includes primarily Chediak-Higashi syndrome (CHS), Griscelli syndrome and Elejalde syndrome. CHS differs from Griscelli syndrome by the presence of abnormal giant cytoplasmic inclusions in leukocytes, most frequent cutaneous pigmentary dilution, aggregates of giant melanolysosomes in melanocytes and keratinocytes, more evenly distributed pigment clumps in hair shafts and more consistently defective granulocyte activity. Elejalde syndrome, also known as neuroectodermal-melanolysosomal disease reveals spotty hair pigmentation similar to Griscelli syndrome with incomplete melanization of melanosomes in skin melanocytes.
The diagnosis of Griscelli syndrome is made by clinical presentation combined with characteristic light and electron microscopic findings in hair shaft and skin and absence of giant cytoplasmic granules in peripheral leukocytes. Prenatal diagnosis has been accomplished by examination of hair from fetal scalp skin biopsies performed at 20 weeks gestation.
The underlying molecular basis for Griscelli syndrome remained elusive until recently, when the genetic locus was found to co-localize on chromosome 15q21 with the myosin-Va gene.
The prognosis for patients with Griscelli syndrome is grave. As in other genetic immunodeficiency diseases, bone marrow transplantation is the only hope for a cure and appears to be most successful when performed early in the course of the disease.
Induction of remission has been obtained with the combination of high dose systemic methylprednisolone and etoposide and intrathecal methotrexate, cytosine arabinoside and prednisolone.
In summary, the silvery-greyish hair associated with fever, pancytopenia and hypertriglyceridemia is the clue to early diagnosis of Griscelli syndrome and important to prevent death before stem cell transplantation.
|1||Griscelli C, Durandy A, Guy-Grand D, Daguillard F, Herzog C, Prunieras M. A syndrome associating partial albinism and immunodeficiency. Am J Med 1978;65:691-702.|
|2||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.|
|3||Mancini AJ, Chan LS, Paller AS. Partial albinism with immunodeficiency: Griscelli syndrome: Report of a case and review of the literature. J Am Acad Dermatol 1998;38:295-300. |
|4||Hurvitz H, Gillis R, Klaus S, Klar A, Gross-Kieselstein F, Okon E. A kindred with Griscelli disease: spectrum of neurological involvement. Eur J Pediatr 1993;152:402-5.|
|5||Elejalde BR, Holguin J, Valencia A, Gilbert EF, Molina J, Margin G, et al . Mutations affecting pigmentation in man. Neuroectodermal melanolysosomal disease. Am J Med Genet 1979;3:65-80.|
|6||Durandy A, Breton-Gorius J, Gay-Grand D, Dumez C, Griscelli C. Prenatal diagnosis of syndromes associating albinism and immune deficiencies (Chediak-Higashi syndrome and variant). Prenat Diagn 1993;13:13-20.|
|7||Pastural E, Barrat FJ, Dufourcq-Lagelouse R, Certain S, Sanal O, Jabado N, et al . Griscelli disease maps to chromosome 15q21 and is associated with mutations in the Myosin-Va gene. Nat Gen 1997;16:289-92.|
|8||Schneider LC, Berman RS, Shea CR, Perez-Atayde AR, Weinstein H, Geha RS. Bone marrow transplantation for the syndrome of pigmentary dilution and lymphohistiocytosis (Griscelli syndrome). J Clin Immunol 1990;10:146-53.|