Griscelli syndrome is a rare autosomal recessive disorder characterized by

albinism Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...

(

hypopigmentation Hypopigmentation is characterized specifically as an area of skin becoming lighter than the baseline skin color, but not completely devoid of pigment. This is not to be confused with depigmentation, which is characterized as the absence of all pi ...

) with immunodeficiency, that usually causes death by early childhood. Researchers have developed three different classifications of the form of disorder, characterised by different signs and symptoms. Type 1 Griscelli Syndrome is assosciated with severe brain function issues along with distinctive discolouring of the hair and skin. Type 2 Griscelli Syndrome have immune system abnormalities in addition to hypopigmentation of skin and hair. Finally, Type 3 is seen as those only affected by hypopigmentation of the skin and hair. This type is not associated with immune deficiencies or neurological abnormalities.

Signs and symptoms

Griscelli syndrome is defined by the characteristic hypopigmentation, with frequent pyogenic infection, enlargement of the liver and spleen, a low blood neutrophil level, low blood platelet level, and immunodeficiency. Very often there is also impaired natural killer cell activity, absent delayed-type hypersensitivity and a poor cell proliferation response to antigenic challenge. This may be caused by the loss of three different genes, each of which has different additional effects, resulting in three types of syndrome. Its inheritance is autosomal recessive. Examination of the hair in this syndrome may be useful. Under light microscopy, these hairs exhibit bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, the hairs appear monotonously white.Valente NY, Machado MC, Boggio P, Alves AC, Bergonse FN, Casella E, Vasconcelos DM, Grumach AS, de Oliveira ZN (2006) Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes. Clinics (Sao Paulo) 61(4):327-332.

Pathophysiology

In melanocytes, melanosomes (

vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry) In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...

s containing the pigment

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

) are transported on

microtubules Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 a ...

. They are then bound by Rab27A which recruits Slac2-a and myosin Va. This complex then transfers the melanosomes from the microtubules to

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

filaments. This transfer is necessary for the transport of melanosomes from the perinuclear area to the cell periphery. The loss of any one of these proteins interrupts melanosome transport and results in the hypopigmentation. However, these three proteins do not work together in other cells and

RAB27A Ras-related protein Rab-27A is a protein that in humans is encoded by the ''RAB27A'' gene. Function The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in prot ...

effectors may be 'mix and match.' For example, the knockout of Rab27 causes the hypopigmentation but also immunodeficiency due to deficiencies in cytotoxic killing activity in cytotoxic T cells (something that also depends on

transport). While, the knockout of myosin Va does not cause immunodeficiency, but it does cause neural defects. Though some neural problems (i.e. brain damage) can be seen in Rab27A deficient children, this is thought to be a secondary effect of the immune problems, and not directly due to the lack of Rab27A. Munc13-4 has also drawn attention based on its involvement in causing bleeding manifestations in Griscelli syndrome.Munc13-4 through its interactions with Rab27a appears to be important for the dense granule release from platelets. The mutated Rab27a interaction with Munc13-4 is the cause of bleeding in type 2 Griscelli Syndrome.

Diagnosis

Types

Griscelli syndrome is a disorder of

melanosome A melanosome is an organelle found in animal cells and is the site for synthesis, storage and transport of melanin, the most common light-absorbing pigment found in the animal kingdom. Melanosomes are responsible for color and photoprotection i ...

transport, and divided into several types:James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. .

Management

Management and treatment is depended upon the type of syndrome one is diagnosed as having. Prognosis for long-term survival is however, relatively poor. Type 2 is usually rapidly fatal within 1 to 4 years without immediate, accelerated treatment. Chemotherapy have achieved remissions however is sometimes ineffective for the treatment of the primary disease and can fail to control relapses. Allogenic bone-marrow transplantation (BMT) is the only known curative treatment in this disease. The severe neurological impairment and retarded development of the human does not improve with time. During the accelerated phase, immunosuppressives can be used to control signs and symptoms. Since its discovery in 1976, only 40 citations have been found in modern literature. In order to treat patients, the aggressive therapy strategy approach must always be taken for acute bacterial infections and prophylactic antibiotics. This assists in minimising possible effects and prolonging life expectancy.

Eponym

It is named after Claude Griscelli, professor of pediatrics at Hôpital Necker Enfants-Malades in Paris (France).

References

External links

* * * {{DEFAULTSORT:Griscelli Syndrome Disturbances of human pigmentation Noninfectious immunodeficiency-related cutaneous conditions Autosomal recessive disorders Rare syndromes Syndromes affecting the skin Diseases of immune dysregulation Inherited disorders of trafficking