Protoporphyria
Introduction
Introduction to protoporphyrin Protoporphyria (protoporphyria), also known as erythrocyte hepatic porphyria, is an abnormal disease of autosomal dominant porphyrin metabolism. Its clinical features are allergic to sunlight in the skin exposed parts of the body since childhood. In the exposed area, the skin has a burning itching, redness, edema, etc. The content of protoporphyrin in red blood cells and feces is too high, but the urine does not contain urinary porphyrin. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: non-infectious Complications: gallstones cirrhosis
Cause
Cause of protoporphyrin
(1) Causes of the disease
1. Porphyrin metabolism disorder of protoporphyrin disease occurs in bone marrow, red blood cells and hepatocyte bone marrow, liver, blood reticular cells and iron chelatase deficiency in fibroblasts (the last in heme biosynthesis process) An enzyme), thus leading to the accumulation of protoporphyrin, the activity of this enzyme in patients is only 10% to 20% of normal people.
2. The disease is an autosomal dominant disease with different manifestations or incomplete penetrance. Most gene carriers do not have symptoms. Therefore, in the family, it is often found that some people have no clinical symptoms, but There are milder biochemical abnormalities in red blood cells, plasma and feces.
3. The biochemical defects caused by genetic factors make the combination of protoporphyrin and erythrocyte globulin very weak. Free protoporphyrin enters plasma from red blood cells and liver, binds to albumin and heme in plasma, bone marrow or liver or Both produce too much protoporphyrin, which absorbs light energy. When the protoporphyrin molecule gradually returns to its original state, the absorbed light energy fluoresces and forms free chemical groups and peroxidation. Things.
(two) pathogenesis
The disease is autosomal dominant, and the ferrous chelatase gene defect located on chromosome 18q21.3 lacks the ferrous chelatase required to catalyze the synthesis of heme from protoporphyrin IX and ferrous ion, resulting in protoporphyrin. IX accumulates too much in the body. Free protoporphyrin can enter the blood from red blood cells and liver, and deposit in the capillary endothelial cells of the skin, causing photosensitivity reaction of the skin. However, protoporphyrin IX has poor water solubility and strong fat solubility on skin and bone. The tissue affinity of the teeth is poor, so the skin damage is light, the bone and teeth are free of protoporphyrin deposition, and the ferrous chelatase deficiency is caused by the mutation of the enzyme coding region, and the clinical and porphyrin metabolism in the family members carrying the same gene defects. The difference is very large. Although most patients with gene defects have abnormal porphyrin metabolism, but there is no clinical symptoms, and the father and son inheritance are rare, it is speculated that more than one allele is determined to determine the clinical manifestations of the disease. More common in women, the reason is unknown.
The protoporphyrin is mainly excreted from the feces through the biliary tract. The liver damage caused by this disease is caused by the deposition of protoporphyrin in the liver tissue. The liver can remove a large amount of protoporphyrin from the plasma, and the liver can secrete a large amount of protoporphyrin. Capillary bile duct obstruction causes cholestasis. The rate of excretion of protoporphyrin from capillary bile duct epithelial cells is limited, which can accumulate protoporphyrin in hepatocytes. Cholesterol interferes with intracellular oxidative phosphorylation, leading to cell death and liver fibrosis.
Prevention
Protoporphyrinosis prevention
Avoid sun exposure and take sun protection measures. Avoid eating light-sensitive foods.
Complication
Protoporphyrin complications Complications gallstone cirrhosis
Mainly complicated by gallstones, individual cases may have chronic intrahepatic bile accumulation and cirrhosis.
Symptom
Symptoms of protoporphyrin disease Common symptoms Urine has more urinary porphyrin photoallergic eczema scarring edema skin necrosis
Most of the patients began to develop symptoms in early childhood, and the disease occurred before the age of 6 years. A few cases can be delayed until puberty. The disease occurs in the strong summer of the sun, and the sun intensity weakens from late autumn to winter, and the symptoms gradually subsided.
The main manifestation is that the skin is allergic to sunlight. After the skin is exposed to strong sunlight, it first feels hot, then itching, tingling, and edema, blisters, erosion, redness, and the symptoms of each patient are very inconsistent. The lighter retreats within 12 to 24 hours, and then exposed to sunlight, there may be repeated episodes. In a few cases, the skin damage gradually turns into chronic eczema. After several weeks, the scars are healed to form scars. The severe symptoms are red and swollen on the nose and cheeks. Skin necrosis and crusting may occur, forming a superficial depression or a line-like smear-like scar of 2 to 4 mm in size, and the skin is slightly thickened after adult, but there is no real scar, a special appearance. Wax-like face, orange-skinned nose, thick and hard cobblestone on the back of the hand, skin symptoms are limited to the exposed area.
Examine
Examination of protoporphyrinosis
1. Blood picture Hemoglobin and hematocrit may be slightly lower than normal, MCV is lower than normal or normal, MCH is slightly reduced, and the life time of red blood cells is normal.
2. Bone marrow The degree of myeloproliferation and bone marrow cell hematopoiesis are in the normal range.
3. The free protoporphyrin in red blood cells exceeds the normal range, and the most common 5.4-81.0 mol/L is the main diagnostic basis of the disease. The protoporphyrin in the plasma increases, the protoporphyrin in the stool increases or normal, and the peripheral blood is examined by fluorescence microscopy. Red blood cells in the bone marrow can be seen in red fluorescence, which is simple and reliable.
4. Other examinations The iron dynamics test showed that the conversion rate of plasma iron and the utilization of iron were normal, the urine color was normal, and the original porphyrin was not contained.
The free protoporphyrin (FEP) in red blood cells increased significantly, mostly in 5.4-81.0 mol/L (normal <0.9), while the FEP caused by iron deficiency anemia rarely exceeded 5.4 mol/L, carrying the gene defects without clinical symptoms. FEP is 03.6mol/L. In patients with severe protoporphyrin liver disease, FEP generally exceeds 24mol/L. In peripheral blood, red blood cells emit red fluorescence under fluorescence microscope, accounting for 5%25%. Porphyrin was positive, urine color was normal, no porphyrin was contained, and protoporphyrin was significantly increased in feces.
According to clinical manifestations, signs can be selected for B-ultrasound, electrocardiogram, X-ray examination.
Diagnosis
Diagnosis and identification of protoporphyrin
Diagnostic criteria
In general, patients have no systemic symptoms. Most patients may have extremely mild anemia. Because a large amount of protoporphyrin is excreted from the biliary tract, a small number of patients may have cholelithiasis in a young age.
The main diagnosis of this disease is based on the obvious photosensitivity damage of the skin in daylight in the clinical manifestations. Laboratory tests have found that the concentration of free protoporphyrin in red blood cells is increased, and the increase of protoporphyrin and protoporphyrin in red blood cells also has reference value. However, the results are not very consistent, so the importance of diagnosis is not as important as the determination of erythrocyte protoporphyrin. Under the fluorescence microscope, the red blood cell red fluorescence is positive, and the urinary protoporphyrin is negative. According to the above conditions, diagnosis can be made.
Differential diagnosis
1. Iron deficiency anemia and lead poisoning diseases, red blood cell porphyrin content also increased. Red blood cell fluorescence reaction test positive results can also occur in iron deficiency anemia and lead poisoning and other diseases, but no skin light-sensitive clinical manifestations, iron deficiency The serum iron of anemia is low, the iron outside the bone marrow can disappear, and the blood and lead lead in lead poisoning can be differentially diagnosed.
2. Patients with porogenic porphyria are also allergic to sunlight and their skin damage is similar, but the latter is autosomal recessive, and its age of onset is more than 1 year old. Red blood cells do not contain excessive protoporphyrin. It contains too much urinary porphyrin, reddish brown reddish brown or brown, urinary porphyrin test positive, skin often hirsutism and hyperpigmentation.
