Week 9: Congenital WBC Problems Pelger-HuëtPelger-Huët Chediak-HigashiChediak-Higashi Alder-ReillyAlder-Reilly Muco-Muco-

polysaccharidosispolysaccharidosis Hurler’s and Hunter’sHurler’s and Hunter’s May-HegglinMay-Hegglin Myeloperoxidase Myeloperoxidase

deficiencydeficiency

Lipid storage disorderLipid storage disorder Gaucher’sGaucher’s Niemann-PickNiemann-Pick Tay-Sach’sTay-Sach’s Fabry’sFabry’s Sea-blue histiocytosisSea-blue histiocytosis

Pelger-Huët Anomaly

Autosomal dominantAutosomal dominant 1:5,0001:5,000 BenignBenign Hypolobulation of PMN, pince-nezHypolobulation of PMN, pince-nez What is a band?What is a band? Pseudo PH in myelodysplasia (MDS) and Pseudo PH in myelodysplasia (MDS) and

some infectionsome infection

Pelger-Huët Anomaly

Chediak-Higashi Disease

Rare autosomal recessiveRare autosomal recessive Abnormal lysosome: myeloperoxidase Abnormal lysosome: myeloperoxidase

positive fused 1positive fused 1oo granules granules Impaired PMN locomotionImpaired PMN locomotion Hypopigmentation, photophobiaHypopigmentation, photophobia Usually die at 5-10 years of age due to Usually die at 5-10 years of age due to

opportunistic and pyrogenic infectionsopportunistic and pyrogenic infections

Chediak-Higashi Anomaly

Alder-Reilly Anomaly

MucopolysaccharidosisMucopolysaccharidosis Autosomal recessiveAutosomal recessive Hurler’s and Hunter’s diseasesHurler’s and Hunter’s diseases Azurophilic granules in one or all cell typesAzurophilic granules in one or all cell types Vacuolated lymphocytes with granules or Vacuolated lymphocytes with granules or

“comma”“comma” Resemble toxic granulationsResemble toxic granulations

Alder-Reilly Anomaly

May-Hegglin Anomaly

Rare autosomal dominantRare autosomal dominant Döhle-like inclusionsDöhle-like inclusions Thrombocytopenia and giant platelets and Thrombocytopenia and giant platelets and

few granules (cause of bruises)few granules (cause of bruises)

May-Hegglin Anomaly

Myeloperoxidase deficiency

Autosomal recessiveAutosomal recessive Enzyme is one of bacterial killing pathway, but Enzyme is one of bacterial killing pathway, but

usually benign because other PMN biochemistry usually benign because other PMN biochemistry fight infectionfight infection

HH22OO22 HOCl (hypochlorite) HOCl (hypochlorite)

Abnormal pattern in MPO based instrument (eg, Abnormal pattern in MPO based instrument (eg, Technicon H-1)Technicon H-1)

Acquired form in some AML, CML and MDSAcquired form in some AML, CML and MDS

Gaucher’s Disease

A kind of lipid storage diseaseA kind of lipid storage disease -glucocerebrosidase deficiency-glucocerebrosidase deficiency Macrophage (wrinkled, striated) with lipid in Macrophage (wrinkled, striated) with lipid in

lymph nodes, spleen, liverlymph nodes, spleen, liver Type 2 (infantile) and type 3 (juvenile) have worse Type 2 (infantile) and type 3 (juvenile) have worse

prognosisprognosis Type 1 (adult) can live longerType 1 (adult) can live longer Pseudo-Gaucher cell seen in CML with Pseudo-Gaucher cell seen in CML with

cholesterol from cell turn overcholesterol from cell turn over

Gaucher’s Disease

Niemann-Pick Disease

Sphingomyelinase deficiencySphingomyelinase deficiency Foamy macrophages with ceroid and Foamy macrophages with ceroid and

sphingomyelinsphingomyelin Many seen in Ashkenazic JewsMany seen in Ashkenazic Jews Commonly fatal by 3 yearsCommonly fatal by 3 years Vacuolated lymphocytes and monocytesVacuolated lymphocytes and monocytes

Niemann-Pick Disease

Tay-Sach’s Disease

RecessiveRecessive -hexosaminidase deficiency-hexosaminidase deficiency Accululation of gangliosides and Accululation of gangliosides and

glycolipidsglycolipids Affect CNSAffect CNS

Fabry’s Disease

X-linked recessive sphyngolipidosisX-linked recessive sphyngolipidosis -galactosidase deficiency-galactosidase deficiency Ceramide trihexose in kidneysCeramide trihexose in kidneys Renal failure, purpuric skin lesions, CNS Renal failure, purpuric skin lesions, CNS

symptomssymptoms

Histiocytosis

Sea-blue histiocytosisSea-blue histiocytosis Mostly benignMostly benign Cerebroside and carbohydrate Cerebroside and carbohydrate

accumulationaccumulation Histiocytes with ceroid pigmentsHistiocytes with ceroid pigments