Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia.

Abstract

BACKGROUND:

Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency caused by defects of the WAS protein (WASP) gene. Patients with WAS typically demonstrate micro-thrombocytopenia.

PROCEDURES:

The report describes seven male infants with WAS that initially presented with leukocytosis, monocytosis, and myeloid and erythroid precursors in the peripheral blood (PB) and dysplasia in the bone marrow (BM), which was initially indistinguishable from juvenile myelomonocytic leukaemia (JMML).

RESULTS:

The median age of affected patients was 1 month (range, 1-4 months). Splenomegaly was absent in four of these patients, which was unusual for JMML. A mutation analysis of genes in the RAS-signalling pathway did not support a diagnosis of JMML. Non-haematological features, such as eczema (n = 7) and bloody stools (n = 6), ultimately led to the diagnosis of WAS at a median age of 4 months (range, 3-8 months), which was confirmed by absent (n = 6) or reduced (n = 1) WASP expression in lymphocytes by flow cytometry (FCM) and a WASP gene mutation. Interestingly, mean platelet volume (MPV) was normal in three of five patients and six of seven patients demonstrated occasional giant platelets, which was not compatible with WAS.

CONCLUSIONS:

These data suggest that WAS should be considered in male infants presenting with JMML-like features if no molecular markers of JMML can be detected.

• Authors: Ayami Yoshimi, Yoshiro Kamachi, Kosuke Imai, Nobuhiro Watanabe, Hisaya Nakadate, Takashi Kanazawa, Shuichi Ozono, Ryoji Kobayashi, Misa Yoshida, Chie Kobayashi, Asahito Hama, Hideki Muramatsu, Yoji Sasahara, Marcus Jakob, Tomohiro Morio, Stephan Ehl, Atsushi Manabe, Charlotte Niemeyer, Seiji Kojima
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 60 Issue 5 Pg. 836-41 (May 2013) ISSN: 1545-5017 [Electronic] United States
• PMID: 23023736 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• KRAS protein, human
• Membrane Proteins
• Proto-Oncogene Proteins
• Wiskott-Aldrich Syndrome Protein
• PTPN11 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• GTP Phosphohydrolases
• NRAS protein, human
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Bone Marrow (pathology)
• DNA Mutational Analysis
• Diagnosis, Differential
• Erythroid Precursor Cells
• GTP Phosphohydrolases (genetics)
• Humans
• Infant
• Infant, Newborn
• Leukemia, Myelomonocytic, Juvenile (diagnosis, genetics)
• Leukocytosis (complications)
• Male
• Membrane Proteins (genetics)
• Myeloid Progenitor Cells
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (genetics)
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins p21(ras)
• Thrombocytopenia
• Wiskott-Aldrich Syndrome (blood, diagnosis, genetics)
• Wiskott-Aldrich Syndrome Protein (genetics)
• ras Proteins (genetics)