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2234 Part XIII Consultative Hematology

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and coworkers, using multiple linear regression analysis, found global metabolic defects have diverse manifestations; especially
transferrin saturation to be the most important predictor of mean prominent are neurologic abnormalities, failure to thrive, and unex-
corpuscular volume, hemoglobin, and zinc protoporphyrin levels in plained metabolic acidosis. Although the hematologic findings may
children with lead poisoning. be overshadowed by the systemic illness, the recognition of a charac-
Two important points emerge from the foregoing information: (1) teristic pattern of signs and symptoms may lead expeditiously to the
children with significant lead poisoning may have neither anemia nor correct diagnosis. Table 152.4 is a compilation of inborn disorders of
microcytosis, and (2) children with documented lead poisoning metabolism that may manifest in infancy or childhood with hema-
406
should be screened for underlying iron deficiency. Discussion of the tologic cytopenias. Additional information regarding metabolic
immediate treatment and long-term management of patients with disorders is available through the Online Mendelian Inheritance in
lead poisoning can be found in a recent review. 405 Man website (http://www.ncbi.nlm.nih.gov/omim).

HEMATOLOGIC ASPECTS OF METABOLIC DISEASES SPLENOMEGALY IN CHILDREN

A number of congenital disorders of metabolism may manifest Splenomegaly is a problem frequently encountered by both pediatri-
hematologic abnormalities as part of the clinical presentation. Such cians and pediatric hematologists. Although the spleen is rarely a site

TABLE Hematologic Manifestations of Metabolic Disease With Onset in Infancy and Childhood
152.4
Category Disease Defect Hematologic Findings Associated Findings
Lysosomal enzyme Gaucher disease type 1 Glucocerebrosidase Anemia, thrombocytopenia Splenomegaly, bone abnormalities,
defects deficiency delayed puberty, lipid-engorged
macrophages (Gaucher cell) in BM
Niemann-Pick disease Acid sphingomyelinase Anemia Feeding difficulties,
type A deficiency hepatosplenomegaly, developmental
delay, neurodegenerative course,
cherry-red macula, lipid-laden
macrophages (foam cells) in BM
Wolman disease Acid lipase deficiency Anemia, thrombocytopenia Emesis, diarrhea, hepatosplenomegaly,
vacuolization of lymphocytes,
lipid-laden macrophages in BM,
adrenal calcification
Aspartylglycosaminuria Aspartylglycosaminidase Neutropenia Recurrent infections, diarrhea, hernias,
deficiency lens opacities, neurologic
abnormalities, vacuolated
lymphocytes
Defects of heme Congenital Uroporphyrinogen III Anemia, thrombocytopenia Hemolysis, staining of diapers,
synthesis erythropoietic cosynthase deficiency photosensitivity, developmental
porphyria delay, splenomegaly, erythrodontia
Erythropoietic Ferrochelatase deficiency Anemia, thrombocytopenia Hemolysis, photosensitivity, neurologic
protoporphyria abnormalities, hepatobiliary
dysfunction
Defect of amino Tyrosinemia type 1 Fumarylacetoacetate Anemia, thrombocytopenia Failure to thrive, emesis, hepatopathy,
acid metabolism hydrolase deficiency neurologic abnormalities, bleeding,
“cabbage-like” odor, renal tubular
dysfunction
Defects of organic Isovaleric acidemia Isovaleryl-CoA Anemia, thrombocytopenia, Acidosis, emesis, neurologic
acid metabolism dehydrogenase deficiency neutropenia, pancytopenia abnormalities, odor of “sweaty feet”
Methylmalonic acidemia Methylmalonyl-CoA mutase Anemia, thrombocytopenia, Acidosis, neurologic abnormalities,
deficiency leukopenia, pancytopenia failure to thrive, emesis
Mevalonic aciduria Mevalonate kinase Anemia, thrombocytopenia Acidosis, cataracts, neurologic
deficiency abnormalities, hepatosplenomegaly
Defects of organic Propionic acidemia Propionyl CoA carboxylase Anemia, thrombocytopenia Ketotic hyperglycinemia, acidosis,
acid metabolism deficiency neutropenia, pancytopenia neurologic abnormalities
Pyroglutamic aciduria Glutathione synthetase Anemia, neutropenia Hemolysis, neurologic abnormalities,
deficiency metabolic acidosis
Membrane Lysinuric protein SLC7A7 gene mutations Anemia, thrombocytopenia, Malabsorption, protein intolerance,
transport defect intolerance leukopenia, pancytopenia hyperammonemia, neurologic
abnormalities, glomerulonephritis,
pulmonary hemorrhage,
hemophagocytosis
Glycolytic pathway Triosephosphate Triosephosphate isomerase Anemia Hemolysis, neurologic abnormalities,
defects isomerase deficiency deficiency myopathy
Phosphoglycerate kinase Phosphoglycerate kinase Anemia Hemolysis, neurologic abnormalities
deficiency deficiency