erythropoietic porphyria
Introduction
Introduction to erythropoietic porphyria Erythropoietic porphyria disease, also known as erythropoietic uroporphyria, congenital erythropoietic porphyria, congenital photoreactive porphyria, first described by Gunther in 1911, also known as Gunther disease. basic knowledge The proportion of illness: 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: anemia systemic lupus erythematosus
Cause
Etiology of erythropoietic porphyria
(1) Causes of the disease
1. Due to the defect of uroporphyrinogen III co-synthetase, hydroxymethylcholinane under the action of uroporphyrinogen III synthetase can not be normally converted into uroporphyrinogen III, hydroxymethylcholinane can be Spontaneous formation of excessive uroporphyrinogen I, urinary porphyrinogen I can not eventually become heme, but oxidized to urinary porphyrin I, urinary porphyrinogen I decarboxylation under the action of uroporphyrinogen decarboxylase to form coproporphyrin The original I, eventually oxidized to coproporphyrin I, normal people synthesized only a few hundred micrograms of type I porphyrin every day, the disease can be synthesized to more than 100mg.
2. The disease is an autosomal recessive disease. The gene of uroporphyrinogen III co-synthesis enzyme is located on the long arm of chromosome 10, and at least 7 different sites of the gene mutation cause the activity of this enzyme. Defects, in which cytosine (C) at position 217 was replaced by thymine (T) mutations, accounting for 26% of the total mutations.
3. Urinary porphyrin I and coproporphyrin I are both red, emitting red fluorescence and destructive photochemical reaction under ultraviolet irradiation at a wavelength of 400 nm, and the skin damage of the patient is related to the fluorescing porphyrin.
(two) pathogenesis
The uroporphyrinogen III synthase gene is located on chromosome 10q25.3-26.3. The types of gene defects in patients include point mutations, insertions and deletions, and there are many types of gene point mutations. Foreign reports have found 22 different point mutations in 39 patients. The high rate is: Cys73Avg, which is 38.5%. The homozygous allele mutation is clinically severe. It usually occurs after birth and depends on blood transfusion. The heterozygous or single allele point mutation has mild clinical symptoms. The mutation leads to a decrease in the activity of uroporphyrinogen III synthetase, which reduces the production of urinary porphyrin III, and the formation of urinary porphyrin I is excessive, and then it is converted into urinary porphyrin in red blood cells, which accumulates in plasma, but urinary porphyrin III The decrease in synthetase activity generally does not affect the synthesis of heme, because its enzyme activity is more than 1000 times greater than that of ALA. ALA is a synthetic restriction enzyme, and only a small amount of uroporphyrin III synthase can meet the needs of heme synthesis. Individual congenital erythropoietic porphyria patients have defects in uroporphyrinogen decarboxylase activity, suggesting that at least some patients may be a syndrome rather than a single genetic defect.
At present, the disease may be a syndrome, which requires two kinds of defects to be clinically ill: one is congenital enzyme deficiency, the vast majority is uroporphyrinogen III synthetase deficiency; the second is congenital or acquired morbid hematopoiesis, However, this view is rarely consistent with clinical practice, because the probability of the simultaneous presence of both defects in the same patient is very low. The best explanation for the occurrence of congenital erythropoietic porphyria in very few adults is the patient's original clinical congenital urine. The porphyrinogen III synthetase is deficient, and a pathogenic hematopoietic disease occurs later. A large amount of porphyrin is released from the young red blood cells, deposited on multiple organ tissues, and undergoes a photoradiation reaction under the irradiation of light to form atomic oxygen to damage the tissue.
Prevention
Erythropoietic porphyria prevention
Patients should avoid exposure to sunlight (since ordinary cloth can not prevent light with a wavelength of about 400nm), wearable special materials such as clothes with zinc oxide or titanium oxide materials, gloves and wide-brimmed hats, preventive applications include Cosmetics such as sputum (such as henna) and dihydroxyacetone may be effective in applying a tan to the skin.
Complication
Complications of erythropoietic porphyria Complications anemia systemic lupus erythematosus
Erythropoietic protoporphyrinosis (EPP), an increase in protoporphyrin in the blood can lead to deposition and excessive accumulation in hepatocytes and gallbladder, resulting in gallstones and varying degrees of liver damage and sclerosis. 2 cases of this disease recurrent 3 to 4 years caused by biliary colic attacks. Some patients have mild anemia. Delayed cutaneous porphyria (PCT), with reports of systemic lupus erythematosus, non-insulin-dependent diabetes mellitus, chronic lymphocytic leukemia, and AIDS. Congenital erythropoietic porphyria (CEP), severe seizures such as extremity contracture, missing ear and nose fingers, cheek scars, eyelid valgus, eye adhesions, scarring alopecia, etc. after multiple episodes.
Symptom
Symptoms of erythropoietic porphyria common symptoms scarring liver function failure keratitis
In the infancy or infancy soon after birth, the patient often finds redness, reddish or deep red (vintage) in the urine. The main clinical manifestations are severe skin light sensitivity, and the skin is exposed to intense sunlight and redness first. Redness, burning sensation, pain, then blisters, ulcers, and finally healing, crusting, severe cases or long-term illnesses cause necrosis and disability of the nose, ears and fingers.
Often hirsutism and skin pigmentation, red or brown teeth, red fluorescence under the ultraviolet light of Wood, can appear keratitis, conjunctivitis and photophobia, severe blindness, common spleen enlargement, can occur to varying degrees Hemolytic anemia, anemia can be very serious, accompanied by hypersplenism, a small number of patients died of liver failure.
Examine
Examination of erythropoietic porphyria
Blood picture
There are different degrees of positive cell angiochromatosis, but anemia is rarely required for clinical blood transfusion, peripheral blood can be seen with abnormal red blood cells, red blood cells vary in size, and more common eosinophilic and basophilic red blood cells and nucleated red blood cells, reticulocytes increase.
2. Bone marrow
The erythroid hyperplasia sometimes shows similar morbid hematopoiesis. Under ultraviolet light, bone marrow nucleated red blood cells and peripheral blood red blood cells show bright red fluorescence due to the increased concentration of porphyrin.
3. Metabolic abnormalities
Urinary porphyrin I excretion in urine increased significantly, urinary porphyrin III and coproporphyrin I excretion also increased, total porphyrin discharge in urine up to 100,000g / 24h (normal <300), while ALA and The biliary discharge was normal, the urine showed red fluorescence under ultraviolet light, the fecal porphyrin I excretion in feces increased, and the concentration of urinary porphyrin I in red blood cells and plasma increased significantly.
4. Erythrocyte osmotic fragility increased, red blood cell life shortened with ineffective hematopoiesis, and plasma iron dynamics showed accelerated iron turnover.
5. According to the condition, clinical manifestations, symptoms, signs, choose to do ECG, X-ray, B-ultrasound and other tests.
Diagnosis
Diagnosis and diagnosis of erythropoietic porphyria
diagnosis
According to the typical clinical and laboratory examination characteristics of the disease, the diagnosis can be established, "red urine" and "red teeth", the destructive skin damage of the light part, accompanied by hairy and pigmentation is a typical clinical feature of the disease, laboratory examination It can be seen that the concentration of urinary porphyrin I in red blood cells, plasma and urine is significantly increased, and positive cells are positively pigmented anemia.
Sensitive skin lesions and red urine may occur in childhood, combined with hemolytic anemia and redness of the teeth, suggesting that the disease, examination of high levels of urinary porphyrin I and red blood cells and bone marrow erythrocytes showed a fluorescent response, to determine the diagnosis.
Differential diagnosis
The disease needs to be differentiated from protoporphyrin, neonatal herpes and solar dermatitis.
