We present the case of 2 sisters who had vastly different phenotypic presentations despite having the same genetic frameshift mutation in the RAB27A gene. [ingentaconnect.com]

GS1 presents with primarily neurologic impairment with no immunologic involvement while GS2 presents with immunological dysfunction and multisystem involvement, whereas GS3 have only hypomelanosis. [ncbi.nlm.nih.gov]

Case presentation A 3-year-old boy, born out of nonconsanguineous marriage, presented with high grade intermittent fever for about 1.5 months. [bmcpediatr.biomedcentral.com]

A very close differential diagnosis of GS is Chediak–Higashi syndrome, which also presents with partial albinism and recurrent infections. [journals.lww.com]

Griscelli syndrome has to be distinguished from Chediak-Higashi syndrome and Elejalde disease, which can also present with silvery hair. [pigmentinternational.com]

• Recurrent Bacterial Infection

  bacterial infections ; Reduced delayed hypersensitivity ; Seizures ; Silver-gray hair ; Spasticity Associated Genes RAB27A (Withdrawn symbols: GS2, HsT18676, RAB27, RAM ) Mouse Orthologs Rab27a (Withdrawn symbols: 2210402C08Rik, 2410003M20Rik, 4933437C11Rik [mousephenotype.org]

  bacterial infections Bacterial infections, recurrent Frequent bacterial infections Increased susceptibility to bacterial infections Recurrent major bacterial infections [ more ] 0002718 Reduced delayed hypersensitivity 0002972 Showing of 46 | Last updated [rarediseases.info.nih.gov]

• Death in Childhood

  HEMOPHAGOCYTIC SYNDROME, PAID SYNDROME, PARTIAL ALBINISM AND IMMUNODEFICIENCY SYNDROME Classification eye, genetic, immunological, skin Phenotypes Abnormal cerebellum morphology ; Accumulation of melanosomes in melanocytes ; Autosomal recessive inheritance ; Death [mousephenotype.org]

  […] available through HPO Abnormal cerebellum morphology Abnormality of the cerebellum Cerebellar abnormalities Cerebellar abnormality Cerebellar anomaly [ more ] 0001317 Accumulation of melanosomes in melanocytes 0001008 Autosomal recessive inheritance 0000007 Death [rarediseases.info.nih.gov]

• Hyperthermia

  Morphology of the bone marrow was hypocellular, signs of dyserythropoiesis (stage I) and megakaryocytes were reduced Methodology According to the clinical and laboratory data(hepatosplenomegaly, increased ferritin, hypertriglyceridemia, pancytopenia, hyperthermia [htct.com.br]

• Ear Discharge

  discharge for last 2 months. [ncbi.nlm.nih.gov]

  The sibling had history of repeated episodes of fever and ear discharge and light colored hair. There was no history of any relatives affected by similar clinical presentation. On examination his vital parameters were normal. [e-ijd.org]

• White Eyelashes and Eyebrows

  He had pallor, silvery gray scalp hair, white eyelashes, sparse eyebrows, and pedal edema [Figure 1]. Abdomen was distended, with firm hepatomegaly. The spleen was palpable 7 cm below left costal margin and was firm in consistency. [ncbi.nlm.nih.gov]

• Sparse Eyebrows

  He had pallor, silvery gray scalp hair, white eyelashes, sparse eyebrows, and pedal edema [Figure 1]. Abdomen was distended, with firm hepatomegaly. The spleen was palpable 7 cm below left costal margin and was firm in consistency. [ncbi.nlm.nih.gov]

• Cerebellar Sign

  In GS2, the lymphohistiocytic infiltration of brain occurs in an accelerated phase, resulting in seizures, hypertonia, hyperreflexia, cerebellar signs, hemiparesis, increased intracranial tension, and loss of acquired milestones. [3], [4] The only cure [neurologyindia.com]

  Neurologic involvement with raised intracranial pressure, cerebellar signs, encephalopathy, hemiparesis, peripheral facial palsy, spasticity, hypotonia, seizures, psychomotor retardation and progressive neurologic deterioration is known [ 3 ]. [casereports.in]

The work up for all these disorders came to be negative and child was referred to our facility for further workup. [ncbi.nlm.nih.gov]

Sepsis workup and CSF study including cytospin for malignant cells were negative. LDH was mildly elevated and serum ferritin, fibrinogen levels, triglycerides were normal ruling out possibility of hemo-phagocytosis [Table 1]. [casereports.in]

Besides, molecular diagnosis should be considered early in the diagnostic workup, which will be valuable for the prompt initiation of treatment and the reduction of late sequelae. [bmcpediatr.biomedcentral.com]

• Anisopoikilocytosis

  The peripheral smear showed moderate anisopoikilocytosis, predominantly normocytic hypochromic RBC with fair number of microcytes, ovalocytes and few ellipitocytes. Platelets and leucocytes were reduced. [ncbi.nlm.nih.gov]

• Lymphocytic Infiltrate

  HLH has been characterized by an unremitting polyclonal CD8+ T-cell expansion, and lymphocytic infiltration of visceral tissues that leads to macrophage activation (hemophagocytosis) and the deleterious release of several cytokines, including interferon [scielo.br]

Palliative care includes treatment and prophylaxis care infections and immunosupressor therapy in accelerated phases. Some patients have died after transplantation, but others have had lasting remissions [htct.com.br]

However, he did not respond to treatment and died. [scielo.br]

HLH-directed therapy followed by HSCT is the only curative treatment for patients with familial HLH, including GS2. [bmcpediatr.biomedcentral.com]

HLH can damage organs and tissues throughout the body, causing life-threatening complications.[10270] GS2 is caused by changes (mutations) in the RAB27A gene and is inherited in an autosomal recessive manner.[10270][10272] The only current treatment that [rarediseases.org]

[…] of skin and hair without any systemic involvement.[6] The prognosis for patients with GS3 is good, and these patients do not require any treatment. [journals.lww.com]

Although phenotypically similar, prognosis of each type varies depending on neurological or hematological findings. [journals.lww.com]

As far as possible HSCT is planning Conclusion The prognosis of patients with Griscelli syndrome is poor. It is usually rapidly fatal within 1-4 years without aggressive treatment and bone marrow transplantation at onset of an accelerated phase. [htct.com.br]

The prognosis of GS2 is poor, with death in early childhood due to HLH and its complications. [cdriadvlkn.org]

Rab27a, Mlph, and MyoVa are proteins involved in the movement of melanosomes. [5] Prognosis and treatment vary among the different groups. Presence of neurological or immunological impairments carries a poor prognosis. [ijpd.in]

[…] and CNS vasculitis) and secondary etiologies (e.g. infections, tumor). [bmcpediatr.biomedcentral.com]

The classical phenotypic picture of silvery gray hair and its light microscopy findings of melanin clumps in the presence of negative CSF analysis and blood culture (to assess for the presence of an infective etiology) is confirmatory for GS2. [neurologyindia.com]

This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. [panafrican-med-journal.com]

^ "Hermansky-Pudlak Syndrome: Background, Pathophysiology, Epidemiology". 13 June 2017. ^ "Hermansky-Pudlak Syndrome". Hermansky–Pudlak Syndrome. University of Washington, Seattle. 1993. [en.wikipedia.org]

Due to its rarity, epidemiologic data are still lacking. Hyperferritinemia is frequently associated with MAS and might modulate the cytokine storm, which is involved in the development of multiple organ failure. [panafrican-med-journal.com]

Hospital & Research Center, Riyadh, Saudi Arabia A Al-Ghonaium, H Al-Mousa, B Al-Saud, S Al-Muhsen & H Al-Dhekri Department of Genetics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia A Hawwari Department of Biostatistics & Epidemiology [nature.com]

Retrieved 24 November 2008. ^ "Hermansky-Pudlak Syndrome: Background, Pathophysiology, Epidemiology". 13 June 2017. ^ "Hermansky-Pudlak Syndrome". Hermansky–Pudlak Syndrome. University of Washington, Seattle. 1993. [en.wikipedia.org]

Figure 3: (a and b) Pathophysiology of Griscelli syndrome and pathogenesis of Griscelli syndrome type 2 Click here to view The genetic abnormality and clinical presentation of the three types of GS are summarized in [Table 1]. [1], [2], [3], [4], [5], [ijpmonline.org]

Notes Declarations Authors’ Affiliations (1) Department of Pathology and Pathophysiology, School of Medicine, Southeast University, Nanjing, 210009, China (2) Department of General Surgery, the Second Affiliated Hospital of Nanjing Medical University, [diagnosticpathology.biomedcentral.com]

These cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection and illness. [ghr.nlm.nih.gov]

The authors concluded that early aHSCT is feasible for treating patients with Griscelli syndrome and low level of donor cell engraftment is sufficient to prevent the recurrence of the disease. [cags.org.ae]

As a result, these structures clump near the center of melanocytes, trapping melanin within these cells and preventing normal pigmentation of skin and hair. [encyclopedia.pub]

Protein coding - H3BS49 - 3' truncation in transcript evidence prevents annotation of the end of the CDS. CDS 3' incomplete Transcript Support Level 3, when transcripts are supported by a single EST only. [ensembl.org]

The genetic mutation affects the transportation of melanosomes thus trapping them in the center of the melanocytes preventing the normal pigmentation of the eyes, hair and skin. [mybiosource.com]