An Indian boy with griscelli syndrome type 2: Case report and review of literature

Abstract

Griscelli syndrome 2 is a rare autosomal recessive disorder of pigmentary dilution of hair, skin, splenohepatomegaly, pancytopenia, immune and neurologic dysfunction. Clinical course is characterized by recurrent infection triggered by uncontrolled T-lymphocyte and macrophage activation, called hemophagocytic syndrome. Since the primary presentation is with depigmented hair, we attempt to highlight diagnostic difficulties in such cases in developing countries like ours where pigmentary changes in hair and skin are commonly attributed to severe malnutrition. We also evaluated phenotype of all 10 cases of genotype (c.C550T; p.R184X), collected from published literature worldwide and emphasize the potential role of above mutation as hotspot in Southeast Asian region.

Griscelli Syndrome in a seven years old girl

“…16 Therefore, GS-II has a poor prognosis and can cause death in early childhood. Bone marrow transplant is the only treatment for these patients, 5 and patients with GS who fail to be transplanted usually die within five years after diagnosis. 17 Most of the GS-II reported cases are from parents with consanguineous marriages.…”

“…Palliative and supportive treatments are suggested in GS1 patients, and GS3 patients require no treatment, and it has a very good prognosis. 5,9,10 Due to different mutations in the RAB27A gene, GS-II clinical symptoms can differ from case to case. 20 Gris celli syndrome type 2 clinical presentations are partial albinism, immunodeficiency, organomegaly, pancytopenia, and lymphohistiocytic infiltrates in various organs (GS2).…”

Whole-Exome Sequencing, Proteome Landscape, and Immune Cell Migration Patterns in a Clinical Context of Menkes Disease

“…Our results showed a remarkable defect in the transmigration capacity of neutrophil cells isolated from the parents, which was aggravated in the patient with MD. Neutrophil function abnormalities, including defects in transmigration capacity, can account for immune deficiencies as seen in CHS or GS-2 syndromes [ 34 , 35 ]. Even when cell adhesion was not evaluated and molecular analysis for the pathways involved remains to be elucidated, it is possible to speculate that migratory defects observed in the proband may be related with a failure to regulate the actin cytoskeleton and vesicle trafficking, unifying this cell component as a key player in MD as observed in neutrophil-related diseases [ 34 , 35 ].…”

Development, characterization, and hematopoietic differentiation of Griscelli syndrome type 2 induced pluripotent stem cells

“…Griscelli syndrome type 2 (GS-2) is a rare, inherited, autosomal recessive disease with a frequency of < 1/1,000,000 in neonates and has been shown to occur more often in Middle Eastern countries, such as Turkey, due to the increased rate of consanguineous marriages [ 1 ]. The disease is characterized by partial albinism (silver-colored hair, eyebrows, and eyelashes), hepatosplenomegaly, pancytopenia, immune deficiency, and neurological dysfunction [ 2 ]. In GS-2, RAB27A mutations cause the malfunction of a small GTPase, which plays an important role in vesicular fusion and cellular trafficking [ 2 ].…”

“…The disease is characterized by partial albinism (silver-colored hair, eyebrows, and eyelashes), hepatosplenomegaly, pancytopenia, immune deficiency, and neurological dysfunction [ 2 ]. In GS-2, RAB27A mutations cause the malfunction of a small GTPase, which plays an important role in vesicular fusion and cellular trafficking [ 2 ]. The RAB27A protein is responsible for the peripheral distribution of melanosomes in melanocytes and exocytosis of cytotoxic granules in the cytosol of cytotoxic T cells (CTL) and natural killer (NK) cells.…”