Partial albinism with immunodeficiency (Griscelli syndrome)

doi:10.1016/S0022-3476(05)82003-7

The Journal of Pediatrics

Volume 125, Issue 6, Part 1, December 1994, Pages 886-895

https://doi.org/10.1016/S0022-3476(05)82003-7 Get rights and content

Abstract

Partial albinism with immunodeficiency is a rare and fatal immunologic disorder characterized by pigmentary dilution and variable cellular immunodeficiency. To define the phenotype, therapy, and outcome, we retrospectively analyzed seven consecutive patients. Primary abnormalities included a silvery-grayish sheen to the hair, large pigment agglomerations in hair shafts, and an abundance of mature melanosomes in melanocytes, with reduced pigmentation of adjacent keratinocytes. Clinical onset occurred between the ages of 4 months and 4 years and was characterized by accelerated phases (lymphohistiocytic infiltration of multiple organs, including the brain and the meninges), triggered by viral and bacterial infections. Characteristic laboratory features included pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and hypoproteinemia. Consistent immunologic abnormalities were characterized by absent delayed-type cutaneous hypersensitivity and impaired natural killer cell function. Some patients had secondary hypogammaglobulinemia, impaired major histocompatibility complex-mediated cytotoxic effects, a decreased capacity of lymphocytes to trigger a mixed lymphocyte reaction, or various functional granulocytic abnormalities. The disease seems to be invariably lethal without bone marrow transplantation; the mean age at the time of death was 5 years. Bone marrow transplantation has been performed in three cases; two patients died in the immediate posttransplantation period of infectious complications, but one patient is cured after a follow-up of 5 years. We conclude that partial albinism with immunodeficiency (Griscelli syndrome) can be differentiated from Chédiak-Higashi syndrome by pathognomonic histologic features. One of the underlying immunologic defects may be a defective function of natural killer cells, predisposing the patient to virus-associated hemophagocytic syndrome or accelerated phases. The prognosis is very poor unless early bone marrow transplantation is carried out. (J PEDIATR 1994;125:886-95)

Section snippets

METHODS

We reviewed the charts of seven patients from five families who were referred between 1982 and 1993 to the Hôpital Necker Enfants Malades, in Paris, or the Hôpital Debrousse, in Lyon. Peripheral blood mononuclear cell isolation, surface marker analysis, lymphocyte stimulation, and mixed lymphocyte reactions were carried out as previously described.¹² Briefly, peripheral blood mononuclear cells were stimulated either with mitogens in 4-day cultures or with antigen and allogeneic cells in 6-day

Genetic features

The seven children belonged to five families of Italian (patients 1 and 7), French (patient 2), Turkish (patient 3), or north African (patients 4 to 6, siblings) origin. Three families were consanguineous. Analysis of the five family trees suggested that partial albinism with immunodeficiency was an autosomal recessive trait. Six affected patients were born to consanguineous parents. A boy and a girl in one family died at ages 4 and 6 years, respectively, with partial albinism and other

DISCUSSION

Our findings confirm the previously described features of partial albinism with immunodeficiency, such as melanocyte abnormalities, absent delayed hypersensitivity, and a severe clinical course characterized by accelerated phases and recurrent infections.¹ In contrast to our original report, which mentions the absence of cutaneous Langerhans cells on electron microscopy, immunofluorescence studies showed their presence. Morphologically, the Langerhans cells appeared normal, particularly with

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^☆: From the Unité d'Immunologie et d'Hématologie, INSERM Unité 132, and the Département d'Anatomie et de Pathologie Pédiatrique, Hôpital Necker Enfants Malades, Paris, the Département de Dermatologie-Centre de Diagnostic des Maladies Bulleuses, Hôpital St. Louis, Paris, and the Département de Pédiatrie, Hôpital Debrousse, Lyon, France.

^☆☆: Supported in part (Dr. Klein) by the Fritz-Thyssen-Stiftung.

^★: Reprint requests: Christoph Klein, MD, University Children's Hospital, Mathildenstrasse 1, D-79106 Freiburg, Germany.

^★★: 0022-3476/94/$3.00 + 0 9/20/58919

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Partial albinism with immunodeficiency (Griscelli syndrome)☆,☆☆,★,★★

Abstract

Section snippets

METHODS

Genetic features

DISCUSSION

Am J Med

Pathol Res Pract

J PEDIATR

Blood

Blood

J PEDIATR

Mendelian inheritance in man

Griscelli-Pruniéras disease (partial albinism with immunodeficiency): report of a new case with light and electron-microscopic study of the skin

Eur J Dermatol

Prenatal diagnosis of syndromes associating albinism and immune deficiencies (Chédiak-Higashi syndrome and variant)

Prenat Diagn

Bone marrow transplantation for the syndrome of pigmentary dilution and lymphohistiocytosis (Griscelli's disease)

J Clin Immunol

Griscelli disease with cerebral involvement

Eur J Pediatr

Partial albinism with immunodeficiency: a rare syndrome with prominent posterior fossa white matter changes

AJNR Am J Neuroradiol

Partial albinism, immunodeficiency, and progressive white matter disease: a new primary immunodeficiency

Allergy Proc

A kindred with Griscelli disease: spectrum of neurological involvement

Eur J Pediatr

A new familial defect in neutrophil bactericidal activity

Helv Paediatr Acta

Immunodeficiency with low expression of the T-cell receptor CD3 complex: effect on T lymphocyte activation

Eur J Immunol

Natural killer and killer cell activities in patients with primary immunodeficiencies or defects in immune interferon production

Eur J Immunol

Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes

J Immunol

Treatment of four patients with erythrophagocytosis by a combination of epipodophyllotoxin, steroids, intrathecal methotrexate, and cranial irradiation

Pediatrics