The low incidence of this syndrome is often related to aldolase A's essential glycolytic role along with its exclusive expression in blood and skeletal muscle.

Typically diagnosed at birth, congenital nonspherocytic hemolytic anemia is characterised by premature destruction of red blood cells without apparent abnormality in shape.

[4] This shortened erythrocyte life-span and increased destruction links to hyperbilirubinemia which often presents as jaundice in the accumulation of bilirubin through excessive hemoglobin breakdown.

[6] Lactate accumulation has also been noted in some patients, potentially linked to reciprocal stimulation of pyruvate kinase, a key enzyme in lactic acid fermentation.

This is often recognized initially through signs of muscle weakness and exercise intolerance, suggesting rapid muscular fatigue and damage, likely directly related to ATP depletion.

This breakdown of muscular fibers, or rhabdomyolysis, can lead to detectable blood creatine phosphate level elevation [9] and potentially exaggerated hyperkalemia.

[4] Delayed growth and development was noted in some patients, although not fully explained, this may be generally associated with the physiological difficulties implicit in errors of energy metabolism.

[10] Elevated liver glycogen in one patent was rationalised through an accumulation of fructose-1,6-bisphosphate leading to impaired glucose metabolism and increased diversion of hexose sugars from peripheral tissues.

A comparable maternal missense mutation wherein tyrosine is replaced by cysteine alters the carboxy-terminus due to its proximity to a crucial hinge structure.

[4] The initial 1973 case is atypical, in that no indication of aldolase A structural abnormality was found in isoelectric focusing, heat stabilization, electrophoresis or enzyme kinetics.

[citation needed] The two familial male patients reported in 1981 (having been born in 1967 and 1979) were from a small Japanese island indicating a similar possibility of consanguinity.