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

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

Pelger-Huët Anomaly

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

Chediak-Higashi Anomaly

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

Alder-Reilly Anomaly

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

May-Hegglin Anomaly

Myeloperoxidase deficiency Autosomal recessive Autosomal recessive Enzyme is one of bacterial killing pathway, but usually benign because other PMN biochemistry fight infection Enzyme is one of bacterial killing pathway, but usually benign because other PMN biochemistry fight infection H 2 O 2  HOCl (hypochlorite) H 2 O 2  HOCl (hypochlorite) Abnormal pattern in MPO based instrument (eg, Technicon H-1) Abnormal pattern in MPO based instrument (eg, Technicon H-1) Acquired form in some AML, CML and MDS Acquired form in some AML, CML and MDS

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

Gaucher’s Disease

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

Niemann-Pick Disease

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

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

Histiocytosis Sea-blue histiocytosis Sea-blue histiocytosis  Mostly benign  Cerebroside and carbohydrate accumulation Histiocytes with ceroid pigments Histiocytes with ceroid pigments