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Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome.

Siedlar M, Rudzki Z, Strach M, Trzyna E, Pituch-Noworolska A, Błaut-Szlósarczyk A, Bukowska-Strakova K, Lenart M, Grodzicki T, Zembala M - Arch. Immunol. Ther. Exp. (Warsz.) (2008)

Bottom Line: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage.Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Cracow, Poland. misiedla@cyf-kr.edu.pl

ABSTRACT

Introduction: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder with an autosomal-dominant pattern of inheritance and low fatality rate but significant lifelong morbidity.

Materials and methods: A 27-year-old mother of two children has been suffering from severe neutropenia and recurrent infections with the diagnosis of sporadic WHIM syndrome established by sequencing the CXCR4 gene and the finding of a heterozygous 1000 C-->T nonsense mutation in the second CXCR4 exon. The first child was an apparently healthy boy delivered at full term. Umbilical cord blood cells were obtained for genetic analysis. Peripheral blood cells were also analyzed at 8 months of life. Both analyses revealed the same mutation as that of his mother. The child was in a good condition, manifesting neutropenia without infections until 11 months of life. He subsequently developed pneumonia requiring a more aggressive treatment. After that, the regular substitution of immunoglobulins (IVIGs) and G-CSF has been preventing serious infections. Six months ago the second boy was delivered who also demonstrated neutropenia without severe infections. Genetic studies using cord blood and also peripheral blood cells in the fourth month showed an identical mutation of the CXCR4 gene as in his mother. Moreover, the mother and her first son demonstrated monocytopenia.

Results: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage. Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.

Conclusions: This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

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Related in: MedlinePlus

Highly cellular bone marrow biopsy of the WHIM-mother, with increased mature neutrophil granulocytes showing prominent nuclear segmentation. Inset: bone marrow smear reveals abnormal nuclear segmentation patterns, including variability in nuclear lobe sizes and unusually slender chromatin filaments connecting the nuclear lobes.
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Fig1: Highly cellular bone marrow biopsy of the WHIM-mother, with increased mature neutrophil granulocytes showing prominent nuclear segmentation. Inset: bone marrow smear reveals abnormal nuclear segmentation patterns, including variability in nuclear lobe sizes and unusually slender chromatin filaments connecting the nuclear lobes.

Mentions: The bone marrow of the mother showed high cellularity with an excess of myeloid cells, mostly hypersegmented (senescent) neutrophils (Fig. 1). A uniform but very narrow paratrabecular rim of promyelocytes was present. Normal topography and undisturbed maturation pattern of erythroid cells and megakaryocytes were noted. There was no increase in lymphoid cells, mast cells, or blasts. Also, minimal widespread reticulin fibrosis and distended blood vessels were seen. Bone marrow and peripheral blood smears confirmed the characteristic abnormalities of granulocytes, with a marked nuclear hypersegmentation, thin and long chromatin filaments connecting the nuclear lobes, and abnormal variability in nuclear lobe sizes.Fig. 1


Familial occurrence of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome.

Siedlar M, Rudzki Z, Strach M, Trzyna E, Pituch-Noworolska A, Błaut-Szlósarczyk A, Bukowska-Strakova K, Lenart M, Grodzicki T, Zembala M - Arch. Immunol. Ther. Exp. (Warsz.) (2008)

Highly cellular bone marrow biopsy of the WHIM-mother, with increased mature neutrophil granulocytes showing prominent nuclear segmentation. Inset: bone marrow smear reveals abnormal nuclear segmentation patterns, including variability in nuclear lobe sizes and unusually slender chromatin filaments connecting the nuclear lobes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2805795&req=5

Fig1: Highly cellular bone marrow biopsy of the WHIM-mother, with increased mature neutrophil granulocytes showing prominent nuclear segmentation. Inset: bone marrow smear reveals abnormal nuclear segmentation patterns, including variability in nuclear lobe sizes and unusually slender chromatin filaments connecting the nuclear lobes.
Mentions: The bone marrow of the mother showed high cellularity with an excess of myeloid cells, mostly hypersegmented (senescent) neutrophils (Fig. 1). A uniform but very narrow paratrabecular rim of promyelocytes was present. Normal topography and undisturbed maturation pattern of erythroid cells and megakaryocytes were noted. There was no increase in lymphoid cells, mast cells, or blasts. Also, minimal widespread reticulin fibrosis and distended blood vessels were seen. Bone marrow and peripheral blood smears confirmed the characteristic abnormalities of granulocytes, with a marked nuclear hypersegmentation, thin and long chromatin filaments connecting the nuclear lobes, and abnormal variability in nuclear lobe sizes.Fig. 1

Bottom Line: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage.Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Cracow, Poland. misiedla@cyf-kr.edu.pl

ABSTRACT

Introduction: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare immunodeficiency disorder with an autosomal-dominant pattern of inheritance and low fatality rate but significant lifelong morbidity.

Materials and methods: A 27-year-old mother of two children has been suffering from severe neutropenia and recurrent infections with the diagnosis of sporadic WHIM syndrome established by sequencing the CXCR4 gene and the finding of a heterozygous 1000 C-->T nonsense mutation in the second CXCR4 exon. The first child was an apparently healthy boy delivered at full term. Umbilical cord blood cells were obtained for genetic analysis. Peripheral blood cells were also analyzed at 8 months of life. Both analyses revealed the same mutation as that of his mother. The child was in a good condition, manifesting neutropenia without infections until 11 months of life. He subsequently developed pneumonia requiring a more aggressive treatment. After that, the regular substitution of immunoglobulins (IVIGs) and G-CSF has been preventing serious infections. Six months ago the second boy was delivered who also demonstrated neutropenia without severe infections. Genetic studies using cord blood and also peripheral blood cells in the fourth month showed an identical mutation of the CXCR4 gene as in his mother. Moreover, the mother and her first son demonstrated monocytopenia.

Results: The results indicate that genetic defects connected with WHIM syndrome may influence not only the granulocyte, but also the monocytic lineage. Moreover, a perinatal diagnosis of WHIM syndrome made by sequencing the CXCR4 gene should be performed in cases where either parent is known to be affected with this disease.

Conclusions: This would facilitate an earlier detection of the deficiency in children, thereby allowing a more comprehensive follow-up and administration of appropriate therapy.

Show MeSH
Related in: MedlinePlus