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

Pediatr Blood Cancer. 2013 May;60(5):836-41. doi: 10.1002/pbc.24359. Epub 2012 Sep 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / pathology
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Erythroid Precursor Cells
  • GTP Phosphohydrolases / genetics
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myelomonocytic, Juvenile / diagnosis*
  • Leukemia, Myelomonocytic, Juvenile / 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
  • Wiskott-Aldrich Syndrome / diagnosis*
  • Wiskott-Aldrich Syndrome / genetics*
  • Wiskott-Aldrich Syndrome Protein / genetics
  • ras Proteins / genetics

Substances

  • 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