By Levi Clancy for Student Reader on
- Genetic disease
- Androgen Insensitivity
- Balanced Rearrangement
- Cancer genetics
- Chromosome Number Abnormalities
- Cystic Fibrosis
- Down Syndrome
- Duchenne Muscular Dystrophy
- Fragile X Syndrome
- Huntington Disease
- Hurler Syndrome
- Penis-At-Twelve Syndrome
- Relative Risk
- Sickle Cell Disease
- Spinal Muscular Atrophy
- Tay-Sachs Disease
- Triplet Repeat Expansions
- Trisomy 13
- Trisomy 18
- Unbalanced Rearrangement
- Uniparental Disomy
- mRNA Splicing Aberrations
A hemoglobinopathy is any disorder of hemoglobin, the red blood cell protein which binds oxygen.
Oxyhemoglobin has a reduced orion (does not carry oxygen); methemoglobin has an oxidized iron (carries oxygen). Methemoglobin reductase reverses the oxidation, thus unloading the oxygen.
Some mutant hemoglobin is resistant to methemoglobin reductase, and the heme iron thus remains permanently oxidized.
Heterozygotes accumulate methemoglobin, leading to asymptomatic cyanosis (blue skin). Homozygotes are completely unable to unload oxygen and have thus not been found.
Separate from reductase-resistant methemoglobin are diseases where hemoglobin has altered oxygen affinity.
For example, Hb Kempsey binds oxygen very strongly and cannot unload oxygen to tissues. Encoded by an autosomal dominant, Hb Kempsey heterozygotes over-proliferate RBCs in an attempt to resolve low oxygen levels in tissues; HB Kempsey is lethal for homozygotes.
Clinically significant structural variants of normal hemoglobin are synthesized in the proper amount, but have structural defects which can cause or interfere any of the mechanisms described below.
Structural variants are typically caused by point mutations, and are responsible for Sickle Cell Disease. Recall that Amino1#Amino2 means 'Amino1' replaced 'Amino2' at position '#' on the polypeptide.
|HbS||Hemolytic Anemia||β Chain: Glu6Val||HbS is responsible for the automosal recessive Sickle Disease Disease.|
|HbC||Hemolytic Anemia||β Chain: Glu6Lys||Oxygenated HbC crystalizes, causing mild hemolysis and circulatory obstruction.|
|HbH||Hemolytic Anemia||β Chain: Phe42Ser||Hb Hammersmith (β4) is unstable, precipatory, hemolytic and autosomal dominant.|
|HbM||Oxygen Transport||β Chain: His92Tyr||Methemoglobin cannot unbind oxygen, causing cyanosis. Autosomal dominant.|
|HbK||Oxygen Transport||β Chain: Asp99Asn||Hb Kempsey cannot unbind oxygen, causing autosomal dominant polycythemia.|
|HbE||Thalassemia||β Chain: Glu26Lys||Autosomal recessive thalassemia due to mutant structure and reduced synthesis.|
|Hemolytic Anemia||Hemolytic anemia (lysis of red blood cells) is typically caused by an unstable hemoglobin. Notable exceptions are HbS (sickle cell hemoglobin) and HbC, which are very stable but still detrimental to RBCs.|
|Oxygen Transport||Altered oxygen trasnport is caused by mutant hemoglobin with increased or decrease oxygen affinity. An example is methemoglobin, which is incapable of releasing bound oxygen (as opposed to oxyhemoglobin, which can reversibly oxygenate).|
|Thalassemia||When one hemoglobin chain is unavailable, abnormal hemoglobin form which do not function properly. This condition -- thalassemia -- causes anemia. Also, hemolysis results from extremely unstable abnormal hemoglobin which may form.|