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Griscelli Syndrome
Author: Doctor Geneviève de Saint-Basile1
Creation Date: March 1996
Update:
November 2001
May 2003
Scientific Editor: Professor Alain Fischer
1
Hôpital Necker enfants malades, Centre d'études des déficits immunitaires héréditaires et acquis, 149
Rue de Sèvres, 75743 Paris Cedex 15, France. [email protected]
Abstract
Keywords
Disease name and synonyms
Diagnostic criteria/ definition
Differential diagnosis
Prevalence
Clinical description
Management and treatment
Etiology
Diagnostic methods
Prenatal diagnosis
References
Abstract
Griscelli syndrome, a rare, autosomal recessive disorder, results in hypopigmentation of the skin and the
hair, the presence of large aggregates of pigment in hair shafts and the accumulation of mature
melanosomes in melanocytes. It is caused by mutations in either the myosin-VA (MYO-VA) or RAB27A
encoding gene. Patients with a RAB27A mutation also exhibit a cytotoxic defect and the appearance of an
uncontrolled T-lymphocyte and macrophage-activation syndrome also known as hemophagocytic
syndrome. In contrast, patients with myosin-Va defect associate hypopigmentation with an early primary
and severe neurological impairment, without immune abnormalities. RAB27A and myosin-5a genes have
been localized to the same chromosomal 15q21 region and encode for proteins, which are key effectors
of intracellular vesicular transport. RAB27A, specifically regulates the cytotoxic granule exocytosis. The
cytotoxic defect caused by RAB27A mutations is responsible for triggering the hemophagocytic syndrome
which is often fatal, and for which the only cure is bone-marrow transplantation.
Keywords
partial albinism, exocytosis, defective cytotoxicity, intracellular trafficking, RAB27A, MYO-VA.
Disease name and synonyms
Griscelli syndrome (GS) (MIM 214450) or partial
albinism with immunodeficiency, is an autosomal
recessive genetic disorder which may have two
different molecular causes: a defective member
of the family of monomeric GTPases, RAB27A
or a myosin VA (MYO-VA) function. Recent data
suggest that one of the two hereditary forms of
this disease (defective RAB27A) is similar to the
partial albinism with immunodeficiency, termed
"PAID syndrome" (MIM 604228), described by
Harfi et al. (1) and that the other form (defective
MYO-VA), is similar to the neuroectodermal
melanolysosomal syndrome reported by Elejalde
(MIM 256710) (2).
Diagnostic criteria/ definition
Clinically, Griscelli syndrome is characterized by
partial pigmentary dilution or albinism with silvery
gray hair, frequent infections, cellular immune
deficiency, neurologic abnormalities, and fatal
outcome caused by an uncontrolled T
lymphocyte
and
macrophage
activation
de Saint Basile G. Griscelli syndrome.Orphanet encyclopedia, May 2003.
http://www.orpha.net/data/patho/GB/uk-griscelli.pdf
1
syndrome, the so-called accelerated phase of
the disorder.
Differential diagnosis
GS differs from the Chediak-Higashi syndrome
(MIM 214500), which also associates partial
albinism with immunodeficiency but with the
presence of giant organelles inclusion bodies in
virtually all granulated cells, a hallmark of this
disease.
In
familial
hemophagocytic
lymphohistiocytosis (MIM 603553), X-linked
lymphoproliferative syndrome (MIM 308240) and
virus-associated hemaphagocytic syndrome,
patients develop an accelerated phase identical
to the one observed in GS (3). However, those
disorders do not involve partial albinism and thus
microscopic examination of the hair shaft
enables GS to be easily differentiated from them.
Prevalence
GS was first described in 2 patients in 1978 by
Griscelli and al (4). Since then, more than 40
cases have been described in the literature (1, 511). GS is very rare in almost all populations,
although most cases reported are from Turkish
and Mediterranean populations.
Clinical description
The age at diagnosis of 20 reported cases of GS
ranged from 1 month to 8 years with a mean of
17.5 months. The single most consistent
dermatoskeletal expression of albinism in GS
patients is a silvery gray sheen to their hair (5,
12). Patients generally have lighter hair than
their unaffected family members. Some patients
present with subtle pigmentary dilution of the
skin and iris but this is not a common feature.