Griscelli syndrome types 1 and 2.

To the Editor: In a recent report, Anikster et al. (2002) identified a RAB27A (MIM 603868) deletion in a kindred with Griscelli syndrome (GS) (MIM #214450). Several patients from this kindred displayed neurological manifestations related to the hemophagocytic syndrome (HPS). On the basis of their study, the authors suggest “that the neurological involvement in these patients with GS occurs secondarily to the hemophagocytic syndrome and that patients with primary CNS complications and MYO5A (MIM 160777) mutations have a related disorder, namely, Elejalde syndrome.” This assertion is certainly correct but surprisingly is presented as new and as an “alternative explanation.” Several previously published reports have unequivocally established that neurological manifestations occurring in patients with GS and caused by RAB27A mutation are related to lymphocyte infiltration of the CNS (Menasche et al. 2000; Pastural et al. 2000; de Saint Basile and Fischer 2001), whereas patient(s) with GS caused by MYO5A mutations exhibit a primary neurological disease, potentially described as Elejalde syndrome, and is unrelated to the hematopoietic lineage, as also observed in Myo5a mutant dilute mice (Pastural et al. 1997, 2000; Sanal et al. 2000; de Saint Basile and Fischer 2001; Ivanovich et al. 2001). The common finding of both conditions is albinism that results from the same mechanism—a defective release of melanosome content to neighboring cells, such as keratinocytes in the skin. MyoVA and Rab27A have been shown to interact in the same molecular pathway, resulting in melanosome transport on actin filament to dock at plasma membrane (Marks and Seabra 2001; Hume et al. 2002; Provance et al. 2002; Seabra et al. 2002). There should not be any confusion left, since patients with partial albinism and manifestations of HPS, with or without neurological involvement, should be screened for RAB27A mutations and treated accordingly, whereas those with partial albinism and a primary neurological disease without HPS should be screened for MYO5A mutations, as discussed elsewhere (Menasche et al. 2000) There are numerous examples of conditions grouped under the same umbrella name (such as “Gaucher disease type I to III”) because of shared biological mechanisms, but that have different outcomes and treatments. Griscelli syndromes 1 and 2 are other examples. Incidentally, in table 1 of the Anikster et al. report, the dilute and ashen murine models have been inverted, potentially causing some confusion.