Week 9: Congenital WBC Problems

1. Pelger-Huët Chediak-Higashi Alder-Reilly Muco-polysaccharidosis Hurler’s and Hunter’s May-Hegglin Myeloperoxidase deficiency Lipid storage disorder Gaucher’s Niemann-Pick Tay-Sach’s Fabry’s Sea-blue histiocytosis Week 9: Congenital WBC Problems

2. Pelger-Huët Anomaly • Autosomal dominant • 1:5,000 • Benign • Hypolobulation of PMN, pince-nez • What is a band? • Pseudo PH in myelodysplasia (MDS) and some infection

3. Pelger-Huët Anomaly

4. Chediak-Higashi Disease • Rare autosomal recessive • Abnormal lysosome: myeloperoxidase positive fused 1o granules • Impaired PMN locomotion • Hypopigmentation, photophobia • Usually die at 5-10 years of age due to opportunistic and pyrogenic infections

5. Chediak-Higashi Anomaly

6. Alder-Reilly Anomaly • Mucopolysaccharidosis • Autosomal recessive • Hurler’s and Hunter’s diseases • Azurophilic granules in one or all cell types • Vacuolated lymphocytes with granules or “comma” • Resemble toxic granulations

7. Alder-Reilly Anomaly

8. May-Hegglin Anomaly • Rare autosomal dominant • Döhle-like inclusions • Thrombocytopenia and giant platelets and few granules (cause of bruises)

9. May-Hegglin Anomaly

10. Myeloperoxidase deficiency • Autosomal recessive • Enzyme is one of bacterial killing pathway, but usually benign because other PMN biochemistry fight infection • H2O2 HOCl (hypochlorite) • Abnormal pattern in MPO based instrument (eg, Technicon H-1) • Acquired form in some AML, CML and MDS

11. Gaucher’s Disease • A kind of lipid storage disease • -glucocerebrosidase deficiency • Macrophage (wrinkled, striated) with lipid in lymph nodes, spleen, liver • Type 2 (infantile) and type 3 (juvenile) have worse prognosis • Type 1 (adult) can live longer • Pseudo-Gaucher cell seen in CML with cholesterol from cell turn over

12. Gaucher’s Disease

13. Niemann-Pick Disease • Sphingomyelinase deficiency • Foamy macrophages with ceroid and sphingomyelin • Many seen in Ashkenazic Jews • Commonly fatal by 3 years • Vacuolated lymphocytes and monocytes

14. Niemann-Pick Disease

15. Tay-Sach’s Disease • Recessive • -hexosaminidase deficiency • Accululation of gangliosides and glycolipids • Affect CNS

16. Fabry’s Disease • X-linked recessive sphyngolipidosis • -galactosidase deficiency • Ceramide trihexose in kidneys • Renal failure, purpuric skin lesions, CNS symptoms

17. Histiocytosis • Sea-blue histiocytosis • Mostly benign • Cerebroside and carbohydrate accumulation • Histiocytes with ceroid pigments