Top 2 Types of Porphyrias | Hemoglobin

The following points highlight the top two types of Porphyrias:- 1. Congenital Porphyrias 2. Acquired Porphyrias

Type # 1. Congenital Porphyrias:

A. Erythropoietic porphyria.

B. Erythropoietic pro-to-porphyria.

C. Erythropoietic coproporphyria.

D. Hepatic porphyria.

(a) Acute intermittent porphyria.

(b) Porphyria variegata.

(c) Hereditary coproporphyria.

(d) Porphyria cutanea tarda.

A. Erythropoietic Porphyria:

i. Highly increased excretion of uroporphy­rin I and, to a lesser extent, coproporphy­rin I in both urine and feces. Both these porphyrins are present in higher concen­tration in the circulating erythrocytes.

ii. Photosensitivity and severe skin lesions from infancy leading to severe deformi­ties of the fingers, nose, ears and eyes.

iii. Excess hair on the face and limbs.

iv. Teeth and bones may be brownish or pink due to porphyrin deposition.

v. Tendency to hemolysis and defective erythropoiesis.

vi. The disease is rare.

B. Erythropoietic Pro-to-porphyria:

i. Increased protoporphyrin and uroporphy­rin in the circulating erythrocytes, the plasma and the feces.

ii. Photosensitivity is the major sign.

iii. Chronic skin lesions may develop.

iv. The condition is much more commonly seen.

C. Erythropoietic Coproporphyria:

i. Large amounts of co-pro-porphyrin III con­taining increased amounts of pro-to-por­phyrins and uroporphyrins are present in the erythrocytes.

ii. Swelling and itching of skin.

iii. The condition is very rare.

D. Hepatic Porphyria:

(a) Acute intermittent porphyria:

(i) Excess of ALA and porphobilinogen in the urine.

(ii) Increase in serum protein-bound io­dine (PBI), some degree of hypercho­lesterolemia and a diabetic type of glucose tolerance curve. The condi­tion is due to a marked increase of hepatic ALA synthase.

(iii) Periodic attacks of abdominal pain which is associated with fever and leukocytosis.

(iv) There may be constipation and severe neurological and psychiatric distur­bances.

(v) Freshly passed urine is often normal in colour but, on standing in sunlight, turns to red wine or black.

(vi) The disease is extremely rare before the age of 15 years and after the age of 60. It is slightly more common in females.

(b) Porphyria variegata:

(i) Increased excretion of porphobilino­gen in the urine during acute neuro­logical manifestations and turns to normal in remission.

(ii) Elevated urinary copro-and uroporphyrins and also fecal pro­toporphyrin.

(iii) Frequent uremia and electrolyte dis­turbances.

(iv) Increased hepatic ALA synthase.

(v) Photosensitivity and cutaneous le­sions.

(c) Hereditary coproporphyria:

(i) Increased urinary output of porpho­bilinogen and ALA during acute at tacks.

(ii) Marked increased excretion of co-pro-­porphyrin III, mainly in the feces, this does not always occur in the urine.

(iii) No increase in erythrocyte porphy­rins.

(d) Porphyria cutanea tarda:

(i) Increased urinary uro-and co-pro-porphyrins. This also occurs in feces which may also contain protoporphy­rin.

(ii) Increased hepatic ALA synthase.

(iii) Frequent rise in serum iron.

(iv) Skin lesions in response to minor trauma.

(v) No pink fluorescence in teeth by ul­traviolet light.

(vi) Abdominal pain with fever.

Type # 2. Acquired Porphyrias:

This disease is caused by:

i. Severe liver diseases.

ii. Ingestion of certain toxins.

Alcoholic cirrhosis often leads to the devel­opment of cutaneous hepatic porphyria. This form is common in Southern African countries. In Tur­key, in 1955, the consumption of wheat contami­nated with hex-achloro-benzene caused an outbreak of this type of porphyria.

Important Biochemical Defects:

i. Increased excretion of uroporphyrin in urine.

ii. Fecal porphyrin level is normal.

iii. ALA and PBG are not found in urine.

Effects of Chemical Substances on Induction of Porphyria:

i. Drugs:

Barbiturates, sulfonamides, chloroquine and sex hormones.

ii. Chemical agents:

Hexachlorobenzene, Di- and tri-chlorophenols, phenobarbital, sulfomethane, chloropropamide, and alcohols; orally administered contracep­tives.

Sickle Cell Anemia:

i. In this case hemoglobin δ appears due to abnormality of β-chain where glutamic acid is replaced by valine at position 6.

ii. The loss of glutamic acid with its two carboxyl groups alters the distribution of +ve and -ve charges on the protein surface and changes its solubility. As a result of this insolubility of Hbs, there occurs viscosity which results in reduced blood flow.

iii. Biochemical Explanation of Sickling:

(a) Though glutamic acid (polar) is re­placed by valine (non-polar) gener­ates the formation of sticky patch on the outside of β-chain.

(b) The sticky patch is present on the oxygenated Hbs (R form) and deoxy­genated Hbs (T form) but never present on oxy-HbA (R form).

(c) On the surface of deoxygenated Hbs (T form) there is complementary site which is not present in oxygenated Hbs (R form).

(d) When HbS is deoxygenated, the sticky patch of HbS can bind with complementary site on the other deoxy HbS. This binding causes the polymerization of deoxy HbS form­ing a long fibrous precipitate and forming sickle cell RBC.

Effects of Sickle Cell Erythrocyte:

i. Sickle cells are more fragile and causes hemolytic anemia and jaundice.

ii. Packing of these abnormal red cells into vessels, specially capillaries of organs cause vascular stasis and anoxic damage to the tissue.

Relation with other Diseases:

i. Persons suffering from sickle cell anemia show an increased resistance to malaria.

ii. Salmonella infection is found more in this disease.

Myoglobinuria:

i. Myoglobin being released from the rup­tured muscle fibers appears in the urine colouring it dark red after massive crush injury.

ii. Myoglobin can be detected in plasma af­ter myocardial infarct and assay of serum enzymes also provides a more sensitive index of myocardial injury.

Hemoglobinopathies:

i. Mutation of certain residues of hemoglobin, e.g., histidines E7 or F8, has serious consequences and mutation of many surface residues far removed from the heme binding site shows no clinical abnormalities.

ii. Sickle cell anemia, the best exception, in which all signs and symptoms arise from mutation of a single polar residue to a nonpolar residue. Sickle cell disease, be­ing characterized by recurring pain and early death arose independently in some locations where malaria was prevalent and is widely distributed among regions. A few patients have been cured by stem cell transplantation.

iii. Drugs, cytokines, transfusion, and dialy­sis in neonates have improved life expect­ancy although adults show chronic organ dysfunction.

Glycosylated Hemoglobin (HbA_1c):

i. Hemoglobin is non-enzymatically glycosy­lated when blood glucose enters the eryth­rocytes.

ii. HbA_1c may be separated from HbA by ion exchange chromatography or electro­phoresis.

iii. Normally about 5 per cent of hemoglobin glycosylated is proportionate to blood glucose concentration. The measurement of HbA_1c thus provides information use­ful for the management of diabetes mellitus.

iv. The raised HbA_1c can guide the physician to select appropriate treatment (e.g., in­creased insulin dosage).