Klein C, Philippe N, Le Deist F, Fraitag S, Prost C, Durandy A, Fischer A, Griscelli C
Unité d'Immunologie et d'Hématologie, INSERM Unité 132, Paris, France.
J Pediatr. 1994 Dec;125(6 Pt 1):886-95. doi: 10.1016/s0022-3476(05)82003-7.
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.
伴有免疫缺陷的部分白化病是一种罕见的致命性免疫疾病,其特征为色素稀释和可变的细胞免疫缺陷。为了明确该疾病的表型、治疗方法及预后,我们对连续7例患者进行了回顾性分析。主要异常表现包括头发呈银灰色光泽、毛干中有大量色素团块、黑素细胞中有大量成熟黑素小体,而相邻角质形成细胞色素沉着减少。临床发病年龄在4个月至4岁之间,其特征为加速期(包括脑和脑膜在内的多个器官出现淋巴细胞组织细胞浸润),由病毒和细菌感染引发。特征性实验室检查结果包括全血细胞减少、纤维蛋白原血症降低、高甘油三酯血症和低蛋白血症。一致的免疫异常表现为迟发型皮肤超敏反应缺失和自然杀伤细胞功能受损。部分患者有继发性低丙种球蛋白血症、主要组织相容性复合体介导的细胞毒性作用受损、淋巴细胞引发混合淋巴细胞反应的能力下降或各种功能性粒细胞异常。若无骨髓移植,该疾病似乎必然致命;死亡时的平均年龄为5岁。已对3例患者进行了骨髓移植;2例患者在移植后不久死于感染并发症,但1例患者在随访5年后治愈。我们得出结论,伴有免疫缺陷的部分白化病(格里塞利综合征)可通过特征性组织学特征与切迪阿克-东综合征相鉴别。潜在的免疫缺陷之一可能是自然杀伤细胞功能缺陷,使患者易患病毒相关噬血细胞综合征或加速期。除非早期进行骨髓移植,否则预后非常差。