Niemann-Pick Diseae

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Clinical Niemann-Pick Disease

Back 1

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Inheritance

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Autosomal recessive; sphingomyelin phosphodiesterase 1 (SMPD 1) gene locus 11 p 15.4 15.1 (types A, B)

Type C gene locus 18p

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Prenatal

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CVS/amniocentesis sphingomyelinase enzyme assay from cultured chorionic villus tissue/amniotic fluid cells

DNA analysis

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Incidence

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Type A most common over 50% are Ashkenazi Jews; a few hundred cases reported; M=F

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Age at Presentation

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Type A infancy

Type B infancy to childhood

Type C childhood

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Pathogenesis

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Mutations in SMPD 1 results in acid sphingomyelinase deficiency in types A and B with subsequent accumulation of sphingomyelin in characteristic foam cells within all organs, increased in brain (except type B), liver, spleen, lymph nodes, and lungs; cholesterol esterification defect in type C with normal sphingomyelinase

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Clinical

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Type A
Skin
Xanthomas; yellow brown, waxy induration on exposed surfaces

Central Nervous System
Progressive psychornotor deterioration, hypotonicity, muscle weakness

Gastrointestinal
Hepatosplenornegaly, emaciated appearance fai lure to thrive, vomiting

Lymphatics
Generalized enlarged lymph nodes

Eyes
Blindness, cherry red spots

Ear Nose Throat
Deafness

Lungs
Bronchopneumonia, infiltration of foam cells

Type B
CNS spared, otherwise similar to type A

Type C
Developmental delay, hepatosplenornegaly, progressive psychomotor deterioration

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D/Dx

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Gaucher disease (p. 310)

Tay Sachs disease

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Lab

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Serum sphingomyelinase assay
Bone marrow biopsy

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Management

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Supportive care parenteral nutrition, antibiotics, transfusions, splenectomy

Bone marrow transplant type B

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Prognosis

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Type A death by 2 to 3 years of age secondary to progressive deterioration, fatal pulmonary infection

Type B death in adolescence; may survive into adulthood

Type C death in adolescence