Autosomal recessive disease caused by a deficiency in
the enzyme glucose phosphate isomerase and clinically characterized by
nonspherotic hemolytic anemia and spontaneous hemolytic crises.
Glucose Phosphate Isomerase Deficiency; Phosphohexose
Isomerase Deficiency; Autocrine Motility Factor Deficiency.
Glucose Phosphate Isomerase deficiency is the third most common
enzymopathy (after Glucose-6-Phosphate Dehydrogenase Deficiency and Pyruvate Kinase
Deficiency) that results in hemolysis.
This autosomal dominant disorder
(19cen-q12) is most symptomatic in cases presenting homozygous or compound
The enzyme glucose phosphate isomerase catalyzes the
interconversion of the second step of the Embden-Myerhof (glucose
metabolism) pathway into fructose-6-phosphate. This enzyme is known as the
rate-limiting factor in the mitochondrial energy pathway.
Patients present with nonspherocytic hemolytic
anemia, most often as spontaneously occuring crises. Jaundice, splenomegaly, and
cholecystitis are often associated. Muscle weakness is reported. The
cardiovascular system is not affected. Neurologically, the presence of
mental retardation and mixed sensory and cerebellar ataxia is noted.
Preoperatively, a complete laboratory
assessment should be conducted to confirm the presence of phosphohexose
isomerase deficiency (essential to the risk of spontaneous hemolytic crises)
and evaluate the level of red cell osmotic fragility. The patient's
hematocrit should be obtained. The presence of reduced leukocyte superoxide
anion production should raise the concern of infection because of reduced
leukocyte bactericidal activity. Patients appear to respond positively to
Chronic Hexokinase Deficiency Hemolytic Anemia: Autosomal
recessive inherited disease characterized by chronic hemolytic anemia associated with
severe deficiency of red cell glucose phosphate isomerase. Some cases of
autosomal dominant transmission have been reported. Like phosphofructokinase
and pyruvate kinase, the hexokinase enzyme is a rate-limiting factor in the
metabolism of glucose in the Embden-Meyerhof pathway. Because glycolysis is
the only source of energy for the red cells, deficiency in hexokinase
results in chronic hemolytic anemia. Few allelic variants have been
described of the chronic form. Fukuoka variant: Reported in the Japanese literature
as the association of chronic glucose phosphate deficiency and a history of
prolonged neonatal jaundice. Iwate variant: Chronic form of hemolytic anemia most
often homozygous in pattern and detected early in life. Homburg variant:
Association of chronic hemolytic anemia and neurologic deficits.
Pyruvate Kinase Deficiency (PKD): Blood disorder characterized by a
deficiency of the enzyme pyruvate kinase. Physical findings include
hemolytic anemia, hyperbilirubinemia, splenomegaly, and/or other
abnormalities. Inherited as an autosomal recessive genetic trait.
Triose Phosphate Isomerase Deficiency: Inherited autosomal
dominant disease presents with several alleles. Triose phosphate isomerase
catalyzes the interconversion of dihydroxyacetone phosphate and
glyceraldehyde-3-phosphate (Embden-Meyerhof glycolytic pathway). Clinically,
the entity is characterized by moderate hemolytic anemia (nonspherocytic;
called Dacie type II), cardiac failure, and sudden cardiac arrest most
probably related to dysrhythmias, developmental retardation, severe myopathy
and hypotonia, jaundice, splenomegaly, cholelithiasis, and recurrent
systemic infection. Patients may have normal intelligence. The spasticity
is the result of a neurologic degenerative process involving the lower motor
neurons and manifests as pyramidal tract ...