Clinical Report

Family analysis of Griscelli syndrome type 2: a case report

  • Qian ZHAO ,
  • Junyu CHEN ,
  • Xuemei TANG ,
  • Xiaodong ZHAO ,
  • Xi YANG
Expand
  • 1. Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Infection and Immunity
    2. Internal Medicine Teaching and Research Office of Children’s Hospital of Chongqing Medical University
    3. Department of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China

Received date: 2023-02-21

  Online published: 2024-04-09

Abstract

Objective To investigate the clinical and immunological features of Griscelli syndrome type 2 (GS2) caused by RAB27A gene defect. Methods The clinical data, biochemical examination and pathological biopsy results of 2 children with GS2 in 1 family were collected. Hair was collected for microscopic examination. Peripheral venous blood was extracted for immune-related gene sequencing, and the RAB27A mutation site in the children and their parents was verified by Sanger sequencing. The expression level of RAB27A protein in peripheral blood mononuclear cells was detected by western blot. Flow cytometry was performed to detect CD107a expression in NK and CTL cells, and an age-matched healthy child was used as control. Results The two patients were siblings, and both presented with postnatal hypopigmentation of hair. The main clinical manifestations of both patients were recurrent fever, recurrent respiratory infection combined with hemophagocytic lymphohistiocytosis (HLH), and the younger sister was accompanied by generalized diffuse target-shaped lesions. Accumulation of irregular melanin clusters in the hair were observed in both patients, and the histopathology of the younger sister's lesions showed an irregular distribution of melanocytes in the basal layer of the epidermis. Gene sequencing identified a homozygous frameshift mutation of c.377delC in exon 5 of RAB27A gene, and the parents were consanguineous and both were carriers. Reduced expression of RAB27A protein and defects in the cytotoxicity of NK cells and CTL were observed in peripheral blood mononuclear cells of both patients. Neither patient received chemotherapy or hematopoietic stem cell transplantation (HSCT) and died of HLH successively. Conclusions The definitive diagnosis of GS2 relies on clinical manifestations and genetic testing, immune function testing also contributes to the diagnosis. Currently, allogeneic HSCT is the only method to cure GS2.

Cite this article

Qian ZHAO , Junyu CHEN , Xuemei TANG , Xiaodong ZHAO , Xi YANG . Family analysis of Griscelli syndrome type 2: a case report[J]. Journal of Clinical Pediatrics, 2024 , 42(4) : 345 -350 . DOI: 10.12372/jcp.2024.23e0117

References

[1] Tengsujaritkul M, Suratannon N, Ittiwut C, et al. Phenotypic heterogeneity and genotypic spectrum of inborn errors of immunity identified through whole exome sequencing in a Thai patient cohort[J]. Pediatr Allergy Immunol, 2022, 33(1): e13701.
[2] Casta?o-Jaramillo LM, Lugo-Reyes SO, Cruz Mu?oz ME, et al. Diagnostic and therapeutic caveats in Griscelli syndrome[J]. Scand J Immunol, 2021, 93(6): 1-7.
[3] Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee[J]. Springer US, 2022, 42(7): 1473-1507.
[4] Kuskonmaz B, Ayvaz D, Gokce M, et al. Hematopoietic stem cell transplantation in children with Griscelli syndrome: a single-center experience[J]. Pediatr Transplant, 2017, 21(7). doi:10.1111/petr.13040.
[5] El-Helou SM, Biegner AK, Bode S, et al. The German National Registry of Primary Immunodeficiencies (2012-2017)[J]. Front Immunol, 2019, 10:1272.
[6] Zhang Q, Zhao YZ, Ma HH, et al. Successful rescue of a lethal Griscelli syndrome type 2 presenting with neurological involvement and hemophagocytic lymphohistiocytosis: a case report[J]. BMC Pediatr, 2021, 21(1): 253.
[7] 黄娇娇, 黄佩, 施晓琦, 等. Ⅱ型Griscelli综合征继发噬血细胞综合征1例并文献复习[J]. 疑难病杂志, 2023, 22(4): 434-435.
[8] 赵夏莹, 胡绍燕, 肖佩芳, 等. 单倍体造血干细胞移植治疗Ⅱ型格里塞利综合征继发性噬血细胞综合征1例[J]. 中华实用儿科临床杂志, 2021, 36(3): 219-221
[9] Izumi T. In vivo roles of Rab27 and its effectors in exocytosis[J]. Cell Struct Funct. 2021, 46(2): 79-94.
[10] Marcenaro S, Gallo F, Martini S, et al. Analysis of natural killer - cell function in familial hemophagocytic lymphohistiocytosis ( FHL ): defective CD107a surface expression heralds Munc13-4 defect and discriminates between genetic subtypes of the disease[J]. 2015, 108(7): 2316-2324.
[11] Walsh TG, Li Y, Wers?ll A, et al. Small GTPases in platelet membrane trafficking[J]. Platelets, 2019, 30(1): 31-40.
[12] Ma X, Zhao J, Li S, et al. Rab27a-dependent exosomes protect against cerebral ischemic injury by reducing endothelial oxidative stress and apoptosis[J]. CNS Neurosci Ther, 2022, 28(10): 1596-1612.
[13] Song L, Tang S, Han X, et al. KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a[J]. Nat Commun, 2019, 10(1): 1639.
[14] Chandravathi PL, Karani HD, Siddaiahgari SR, et al. Light microscopy and polarized microscopy: a dermatological tool to diagnose gray hair syndromes[J]. Int J Trichology, 2017, 9(1): 38-41.
[15] Ridaura-Sanz C, Durán-McKinster C, Ruiz-Maldonado R. Usefulness of the skin biopsy as a tool in the diagnosis of silvery hair syndrome[J]. Pediatr Dermatol, 2018, 35(6): 780-783.
[16] Ohishi Y, Ammann S, Ziaee V, et al. Griscelli syndrome type 2 sine albinism: unraveling differential RAB27A effector engagement[J]. Front Immunol, 2020, 11: 612977.
[17] Woodward KE, Shah RM, Benseler S, et al. Considering immunologic and genetic evaluation for HLH in neuroinflammation: a case of Griscelli syndrome type 2 with neurological symptoms and a lack of albinism[J]. Pediatr Blood Cancer, 2020, 67(8): 3-5.
[18] Pachlopnik Schmid J, Ho CH, et al. A Griscelli syndrome type 2 murine model of hemophagocytic lymphohistiocytosis (HLH)[J]. Eur J Immunol, 2008, 38(11): 3219-3225.
[19] Gazit R, Aker M, Elboim M, et al. NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome[J]. Blood, 2007, 109(10): 4306-4312.
[20] I?ikay S. Cerebellar involvement of Griscelli syndrome type 2[J]. BMJ Case Rep, 2014, 2014: 1-2.
[21] Zondag TCE, Torralba-Raga L, Van Laar JAM, et al. Novel RAB27A variant associated with late-onset hemophagocytic lymphohistiocytosis alters effector protein binding[J]. J Clin Immunol, 2022, 42(8): 1685-1695.
[22] Meeths M, Bryceson YT, Rudd E, et al. Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations[J]. Pediatr Blood Cancer, 2010, (54): 562-572.
[23] Al-Mofareh M, Ayas M, Al-Seraihy A, et al. Hematopoietic stem cell transplantation in children with Griscelli syndrome type 2: a single-center report on 35 patients[J]. Bone Marrow Transplant, 2020, 55(10): 2026-2034.
Outlines

/