Partial Albinism, Immunodeficiency, and Progressive White Matter Disease: A New Primary Immunodefiency

Abstract

We studied 12 children who presented with a recently recognized syndrome. The salient features of this new syndrome were recurrent fever; hepatosplenomegaly; pancytopenia: blond, golden to silvery gray hair; hypopigmented skin, progressive white maller demyelination; and early death. Seven patients died, four with severe central nervous system (CNS) involvement, and three with bone marrow failure and sepsis. Cutaneous anergy to recall antigens was present in all patients. Other immunological abnormalities were poor antibody Allergy Proc. istic distribution of melanin with melanocytes present in normal numbers but with fewer short dendritic processes. Langerhans' cells were present in normal numbers in some patients and sparse in others. This syndrome seems to cluster into two tribes from two d(fferent geographical areas in the ArabianPeninsula. In the eight families studied, 12 other siblings and close relatives were found to be affected. The mode of inheritance in this syndrome is that of an autosomal recessive pattern. We propose the term "PAID syndrome" to identify patients with the above features. (Allergy Proc 13, 6: 321-328, 1992)

Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation

“…The Rab‐GTPase, Rab27a, is associated with a genetic disorder leading to disease in humans. Genetic defects in the Rab27a gene cause a rare defect in patients known as Griscelli syndrome type 2 (GS2), which is characterized by pigmentary disorder associated with melanosome transport and severe immunodeficiency associated with defects in T cell, neutrophil, and natural killer cell function …”

“…Genetic defects in the Rab27a gene cause a rare defect in patients known as Griscelli syndrome type 2 (GS2), which is characterized by pigmentary disorder associated with melanosome transport and severe immunodeficiency associated with defects in T cell, neutrophil, and natural killer cell function. [34][35][36][37][38] All of the functions of neutrophils rely on the correct trafficking of their different vesicular compartments and the delivery of their cargo to acceptor membranes or compartments. In this review, we will discuss how various Rab family members along with their effectors regulate trafficking of different granules subsets and consequently modulate neutrophil functions.…”

Regulation of vesicular trafficking and leukocyte function by Rab27 GTPases and their effectors

“…GS2 is a primary immunodeficiency with partial albinism [5,6]. Patients with GS2 develop a disorder characterized by malfunctioning of CTLs, impaired NK cell function [5,6] and defective neutrophil functions [6,7]. At the cellular level, defects in hematopoietic cells are caused by the inability of CTLs, NK cells, and neutrophils to secrete intragranular proteins into infected cells or the extracellular milieu as a result of deficient priming and fusion of secretory organelles.…”

“…Two early case reports suggested that patients with GS have defects in the function of their granulocytes [6,7]. One of those studies showed abnormal bactericidal activity in some of the patients evaluated [6], whereas the other work reported abnormalities in the phagocytic activity of neutrophils only in a subpopulation of the patients under study [7]. Although those studies supported the idea that the function of neutrophils is impaired in Rab27a deficiency, further studies were necessary to increase our knowledge of the role played by this GTPase and its effector molecules in neutrophil function.…”

“…Two early case reports suggested that patients with GS have defects in the function of their granulocytes [6,7]. One of those studies showed abnormal bactericidal activity in some of the patients evaluated [6], whereas the other work reported abnormalities in the phagocytic activity of neutrophils only in a subpopulation of the patients under study [7].…”