Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II.
Griscelli syndrome (GS) was diagnosed in a 2-year-old patient with oculocutaneous albinism and immunodeficiency, but sequencing of RAB27a revealed only a heterozygous mutation. Due to impaired natural killer (NK) and T-cell cytotoxicity implying a high risk of developing hemophagocytic lymphohistiocytosis (HLH), he was prepared for hematopoietic stem cell transplantation (HSCT). Unexpectedly, a severe bleeding episode occurred that led to the demonstration of disturbed platelet aggregation, reduced plateletdense granules, and impaired platelet degranulation. In combination with neutropenia, this suggested the diagnosis of Hermansky-Pudlak syndrome type II (HPSII) and a novel homozygous mutation in AP3B1 was detected. None of the 3 reported HPSII patients had developed HLH, and our patient seroconverted to Epstein-Barr virus (EBV) without clinical symptoms. HSCT was therefore withheld, and granulocyte-colony-stimulating factor (G-CSF) therapy was initiated and prevented further bacterial infections. At 3 years of age, however, the patient developed, without an obvious trigger, fulminant HLH that was resistant to therapy. This patient shows that careful clinical and molecular diagnosis is essential to differentiate the complex disorders of lysosomal trafficking. HPSII belongs to the group of familial hemophagocytic syndromes and may represent an indication for HSCT.
Enders
Anselm
A
Center for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
Zieger
Barbara
B
Schwarz
Klaus
K
Yoshimi
Ayami
A
Speckmann
Carsten
C
Knoepfle
Eva-Maria
EM
Kontny
Udo
U
Müller
Christoph
C
Nurden
Alan
A
Rohr
Jan
J
Henschen
Matthias
M
Pannicke
Ulrich
U
Niemeyer
Charlotte
C
Nurden
Paquita
P
Ehl
Stephan
S
D033963:Adaptor Protein Complex 3 / Q000235:genetics; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D002675:Child, Preschool; D017809:Fatal Outcome; D005434:Flow Cytometry; D022861:Hermanski-Pudlak Syndrome / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D010974:Platelet Aggregation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits