Hematological Abnormalities & Inborn Errors

Bone Marrow Suppression

• Mechanism:  probably direct marrow toxic effect; worse with poor metabolic control, eg:
• proprionic aciduria
• methylmalonic aciduria, including Cbl A, B
• maple syrup urine disease
• isovaleric aciduria
• multiple carboxylase deficiency
• glutaric acidemia type II
• valproic acid

Megaloblastic Anemia

• B12 and folate disorders (mechanism: decreased thymidine synthesis by decreasing methyl-THF)
• Cobalamin metabolic defects, types C,D,E and G
• Cobalamin absorption/transport defects
• Transcobalamin II deficiency
• Cbl F mutation
• Immerslund-Graesbeck syndrome
• Methionine synthetase deficiency
• Defects of folate uptake
• Glutamate foriminotransferase deficiency
• Disorders of pyrimidine synthesis
• Orotic aciduria
• Other
• Homocytinuria
• On the basis of enhanced folate losses
• Thiamine-responsive anemia with diabetes and deafness
• Unknown mechanism
• Lesch-Nyhan syndrome
• purine metabolism disorder

Hemolytic Anemia

• Glutathione synthetase deficiency
• gamma-glutamylcysteine synthetase deficiency
• galactosemia (uncommonly)

Normocytic Anemia

• Hereditary tyrosinemia
• Mechanism: impaired heme synthesis

Neutropenia/neutrophl functional defects

• Glycogen storage disease Type Ib (mechanism ?)
• Glutathione synthetase deficiency
• Galactosemia
• ? Transcobalamin II deficiency

Bleeding Tendency

• GSD types Ia and Ib (?platelet dysfunction)
• ? organic acidemia when ill

Thrombotic Tendency

• Homocyteinuria
• Cystathione synthetase deficiency
• Cbl C, D, ?G
• MTHFR mutation (common in adults)