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Case Report Indian Pediatrics 2004; 41:734-737 |
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Mamta Manglani
Abstract: Griscelli syndrome is a rare autosomal recessive disorder characterized by partial albinism with variable immunodeficiency. Silvery gray hair with large, clumped melanosomes on microscopy of hair shafts are diagnostic. The commonest complication leading to mortality includes lymphohistiocytic proliferation in various organs, including the brain. We present a child with classic clinical features and confirmatory findings of clumped melanosomes on microscopy of hair shaft. Key words: Griscelli syndrome, hemophago-cytosis, lymhohistiocytic proli-feration. Griscelli syndrome (Partial albinism with variable immunodeficiency) is an uncommon disorder characterized by pigmentary dilution and variable cellular and humoral immunodeficiency(1). It is inherited as an autosomal recessive disorder. Features include hepatosplenomegaly, silvery gray sheen to the hair, large clumped melanosomes in hair shafts, pancytopenia, hepatitis and immunologic abnormalities. As of January 2003, 60 cases have been described in world literature(2,3). Case Report A one year and ten-month-old child was referred to us for severe pallor. Her chief complaints were fever (3 months off and on), abdominal distension (2 months), jaundice (1 month), and anasarca (15 days). There was a past history of jaundice and abdominal distension, 4 months prior to this episode, which resolved spontaneously. There was no history of vomiting, urinary or bowel complaints, or bleeding from any site. There was no history of tranfusions received in the past. There was a history of death of the first female sibling at 6 months age with fever. This sibling, on enquiry, also had light coloured hair. On examination, her vital parameters were normal. She had significant pallor, silvery gray hair (Fig. 1), low set ears and insignificant lymphadenopathy. Abdomen was distended, with the liver 6.5 cm palpable, firm and non-tender. The spleen was palpable 7 cm below left costal margin and was firm in consistency. The skin, iris and retina had normal pigmentation. Rest of the physical examination was unremarkable.
Investigations revealed a hemoglobin of 5.5 g/dL, a total leucocyte count 8 × 103/mL, a platelet count of 83 × 103/mL and a reticulo-cyte count of 8.8%. There were no giant cytoplasmic granules in leucocytes. Serum bilirubin was 0.5 mg/dL, total proteins were 8.4 g/dL with albumin –3.8 g/dL, globulins –4.6g/dL and ALT –68 IU/L. Prothrombin time was 22/11 seconds (Internationalized Normalized Ratio of 2.1), PTTK (Partial Thromboplastin Time) –47.5/37.5 seconds and TT (Thrombin Time) –26.5/23.1 seconds. Plasma fibrinogen level was 223 mg/dL and D-dimers were negative. HBsAg, and antibodies for HIV and HCV were negative. Bone marrow aspiration and biopsy were done during the accelerated phase of the disease (Griscelli syndrome) for suspected hemo-phagocytosis. It showed gametocytes and trophozoites of P. vivax with mild megalo-blastic and dysplastic changes, but did not reveal hemophagocytosis. The serum triglycerides, plasma fibrinogen and serum albumin were normal. CD4 counts were 788/mL (NR : 1020 to 3600/mL), CD8 - 1425/mL (NR: 570 to 2230/mL) and CD3 - 2522/uL (NR:1460 to 5440/mL), which suggested moderate immunosuppression (as per 1994 Revised CDC criteria for children infected with HIV). Her serum IgG and IgM were elevated–1770 mg/dL (NR - 350 to 1180) and 701 mg/dL (NR - 36 to 104) respectively and IgA was 55.7 mg/dL (NR 36 to 165). MRI brain showed patchy areas of altered signal intensity in both cerebral hemispheres and left cerebellar hemisphere, with focal signal abnormalities in the right lentiform and left dentate nucleus, suggestive of lympho-histiocytic infiltration. These were consistent with findings seen in Griscelli syndrome. Microscopic examination of the hair shaft showed large unevenly distributed melanin aggregates diagnostic of Griscelli syndrome. The child was treated with antimalarials (quinine and mefloquine) and packed red cell transfusion initially. She responded to mefloquine. However, during her stay she deteriorated neurologically (suggestive of lymphohistiocytic infiltration), for which she was treated with systemic high dose methylprednisolone (30 mg/kg/day for 3 days). She improved and was discharged. She got readmitted within a month with severe anemia and was again given packed red cell transfusions. However, she continued to deteriorate neurologically over the next few days and despite repeated courses of methylprednisolone, she succumbed to the disease within four months after diagnosis. Discussion Griscelli, et al.(4) described two patients with partial albinism in 1978. As of January 2003, 60 cases have been reported(2). Most patients are diagnosed between 4 months and 7 years of age(1). The genetic defects include mutations in either MYO 5A or RAB 27A, both located on chromosome 15q21(5,6). It is characterized by partial albinism, variable cellular and humoral immunodeficiency and the occurrence of "accelerated phases" consisting of hemophagocytosis, pancyto-penia, elevation of serum triglyceride levels, hypofibrinogenemia and hypoproteinemia. Dermatologic findings may be limited to hair, with skin and retinal pigmentation being occasionally affected. Microscopic examination of hair reveals uneven clusters of aggregated melanin pigment, accumulated mainly in the medullary area of the shaft. Neurologic involvement with raised intra-cranial pressure, cerebellar signs, encephalopathy, hemiparesis, peripheral facial palsy, spasticity, hypotonia, seizures, psychomotor retardation and progressive neurologic deterioration is known(7). Immunologic abnormalities include natural killer (NK) cell function defect with absent delayed type hypersnsitivity(8). Secondary hypogamma-globulinemia can occur in accelerated phases, which are characterized by lymphohistiocytic infiltration of various organs mimicking hemophagocytosis. These are thought to be associated with EBV infection, although various other viral and bacterial pathogens have also been incriminated(8). They result from abnormal cytotoxicity function of T and NK cells resulting from inability to secrete cytotoxic granules when the RAB 27A is not functional. The differential diagnosis includes Chediak-Higashi syndrome (CHS) and Elejalde syndrome. CHS differs from GS by presence of abnormal giant cytoplasmic granules in leucocytes, more frequent cutaneous involvement, smaller, more evenly distri-buted pigment clumps in hair shafts and more consistent defective granulocyte activity(3). Elejalde syndrome, like GS has presence of spotty hair pigmentation, but incomplete melanization of melanosomes in skin, and no immunodeficiency(9). The prognosis of patients with Griscelli syndrome is grave. Curative hope is offered only by bone marrow or stem cell transplantation, which is more successful when, performed early in the course of the disease(8). Palliative manage-ment includes treatment of associated infections, and immunomodulatory therapy during accelerated phases (high dose systemic methylprednisolone, etoposide, intrathecal methotrexate, cytosine arabino-side and prednisone, or ATG, cyclosporine and steroids)(8,10). Acknowledgements We wish to express our gratitude to Dr. M.E. Yeolekar, Dean, and Dr. Madhuri Kulkarni, Head of the Department, for permitting us to publish this case report. Contributors: MM diagnosed and managed this patient. She revised the manuscript and finalized the draft. KA also managed the patient and prepared the draft manuscript. BS diagnosed the patient, assisted in management as well as reviewed literature. Funding: None. Competing interests: None stated.
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