Red cell aldolase deficiency
| Aldolase A deficiency | |
|---|---|
 |
|
| Aldolase A deficiency has an autosomal recessive pattern of inheritance | |
| Classification and external resources | |
| Specialty | endocrinology |
| ICD-10 | E74.1 |
| OMIM | 611881 |
| DiseasesDB | 29873 |
| Orphanet | 57 |
Aldolase A deficiency, also called ALDOA deficiency, red cell aldolase deficiency or glycogen storage disease type 12 (GSD XII) is an autosomal recessivemetabolic disorder resulting in a deficiency of the enzyme aldolase A; the enzyme is found predominantly in red blood cells and muscle tissue. The deficiency may lead to hemolytic anaemia as well as myopathy associated with exercise intolerance and rhabdomyolysis in some cases.
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. Early developmental reliance and constitutive function prevents severe mutation in successful embryos. Infrequent documentation thus prevents clear generalisation of symptoms and causes. However five cases have been well described. ALDOA deficiency is diagnosed through reduced aldoA enzymatic activity, however, both physiological response and fundamental causes vary.
Blood-related pathology is seen in all patients. Typically diagnosed at birth, congenital nonspherocytic hemolytic anemia is characterised by premature destruction of red blood cells without apparent abnormality in shape. Erythrocyte dependency on anaerobic glycolysis for ATP homeostasis, causes perturbation of this pathway to result in disruption of cellular processes including electrostatic membrane gradients (typically maintained through transporters of high energetic demand) ultimately leading to membrane instability and lysis.
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. Another side effect of cellular rupture both in the form of hemolysis and rabdomyolysis is excessive plasma concentrations of electrolytes such as potassium. This can lead to hyperkalemia, potentially of great cardiac concern.
...
Wikipedia