Albinism with immunodeficiency characterized by
partial pigmentary dilution of the skin and hair (silvery gray hair),
frequent infections, neurologic abnormalities, and fatal outcome caused by
uncontrolled T lymphocyte and macrophage activation. Clinical
features include the presence of large clumps of pigment in hair shafts and
a pathological accumulation of melanosomes in melanocytes. Two types are described: type
I with severe neurologic impairment and type II with immunologic deficiency.
- Type I: Griscelli Syndrome with Neurologic Impairment; Partial Albinism and
Primary Neurologic Disease without Hemophagocytic Syndrome; Cutaneous and
Neurologic type of Griscelli Syndrome.
- Type II: Chediak-Higashi-Like Syndrome; Partial Albinism Immunodeficiency Syndrome; PAID
Approximately 60 cases have been described; most
reported cases are from Turkish and other Mediterranean populations. The age at
diagnosis ranged from 1 month to 8 years, with a median of 17.5 months (in
Autosomal recessive disorder. The responsible gene is located on
Histopathology of Griscelli syndrome (GS) involves
prominent, mature melanosomes in skin and hair follicle melanocytes, but
sparse pigmentation of adjacent keratinocytes. This leads to large, clumped
melanosomes in hair shafts, resulting in hair that has a silvery-gray sheen.
Type I is caused by mutation in the MyoVa (Myo5a)-gene, which is involved
in melanocytic and neuronal cell vesicle transport.
Type II is caused by mutations in the
RAB27A gene, which encodes for a membrane-bound protein that is involved in signal
transduction and similar to, or in combination with MyoVa, in the melanosome transport.
Immunodeficiency often involves impaired natural killer cell
activity, absent delayed-type hypersensitivity, and a poor cell
proliferation response to antigenic challenges. The two genes encode for
proteins, which are key effectors of intracellular vesicular
transport. RAB27A seems also to be involved in the cytotoxic granule exocytosis.
The single most consistent dermatological expression of
albinism is the presence of silvery-gray hair. GS must be considered for any
child with combined hypopigmentation and neurologic abnormalities (type I)
or what is called hemophagocytic lymphohistiocytosis, (the acute phase of severe
infections may be characterized by an uncontrolled activation of macrophages and
lymphocytes, which is also called the accelerated phase)
(type II). Microscopy examination of the
hair shaft provides strong support for the diagnosis of Griscelli syndrome.
The characteristic neurologic symptoms and analysis of lymphocyte cytotoxic
activity of patients tend to incriminate one of the two molecular causes.
Confirmation by DNA analysis.
Features include partial pigmentary dilution or
albinism with silvery-gray hair, and down-slanted palpebral fissures. Type I is
characterized by severe neurologic impairment (hypotonia, absence of
coordinated voluntary movements and severely retarded psychomotor development,
isolated congenital cerebellar atrophy) presenting early in life. Type II is characterized by
frequent infections, cellular immune deficiency, and fatal outcome caused by
an uncontrolled T-lymphocyte and macrophage activation syndrome. This is the
accelerated phase (fever, jaundice, hepatosplenomegaly, lymphadenopathy,
pancytopenia, and generalized lymphohistiocytic infiltrates of various
organs, including the central nervous system) called hemophagocytic lymphohistiocytosis or hemophagocytic ...