hereditary sideroblastic anemia
Introduction
Introduction to hereditary iron granulocyte anemia Most patients with hereditary iron granulocyte anemia are male except for a few typical cases. Anemia occurs after birth or in infants. Most of them have anemia around 10 to 20 years old, and occasionally they are found after 50 to 60 years old. A family with autosomal inheritance can also be ill. basic knowledge The proportion of illness: 0.002% Susceptible people: mostly male Mode of infection: non-infectious Complications: Diabetes Arrhythmia
Cause
Causes of hereditary iron granulocyte anemia
X chromosome with sexual inheritance (30%):
This type is the most common type. Most of the patients are male. Female carriers suppress the expression of pathological genes due to normal alleles, and there are fewer abnormalities in red blood cells. Therefore, only males in this family have anemia, and female carriers generally There is no anemia, but the red blood cell population is often biphasic. In addition, the family neutrons are only female, may be X-linked dominant inheritance, because men can not survive, and no male patients appear, currently in X sex inheritance The aspect has not been fully finalized.
Autosomal inheritance (30%):
Some families show vertical inheritance between father and son, while others find that brothers and sisters have the same disease, and the extent is the same, suggesting that the genetic pattern is autosomal recessive or autosomal dominant.
Pathology (30%):
In the mitochondria of red blood cells, as the first step of porphyrin biosynthesis, glycine and succinic acid coenzyme A combine to form -amino gamma keto valeric acid (ALA), and pyridoxine (vitamin B6) is converted into biological activity in vivo. Pyridoxal 5-phosphate (PLP), which is a coenzyme that is indispensable for the synthesis of ALA, participates in this reaction. There is evidence that the disease is due to genetic defects in this biochemical process, and biochemical defects in each family. Not necessarily the same.
Some cases suggest a defect in ALA synthase. In some cases, the activity of ALA synthase is low. When the activity of the enzyme is restored after treatment with pyridoxine, even higher than normal, the reaction is similar to vitamin B6 deficiency, but the patient has no diet deficiency. Evidence of metabolic deficiency, and the therapeutic dose needs to exceed the physiological requirement of 1.5 to 2 mg/d, and the effect is often only partially effective. Recently, it has been reported that a point in the family that ALA synthase gene that causes amino acid change is confirmed Mutation, it is now clear that the gene is located on Xp11.2, this family is an X-linked pyridoxine treatment-effective iron granule anemia, DNA sequence analysis of 2 male patients and 1 female carrier In guanine 1215 (exon 8), guanine replaces cytosine, resulting in the replacement of threonine by serine in amino acid residue 388 of ALA synthetase, which is close to the lysine bound to PLP. In the expression, the activity of the mutant enzyme was found to be lower than that of the wild type. The attenuation of the enzyme was similar in the two patients, and the expression of the enzyme activity was similar after the pyridoxine was provided. This mutation resulted in the end of the ALA synthase active center. Structural changes have become a basic defect in this disease. Another case of X-linked iron granulocyte anemia is associated with abnormality of phosphoglycerol kinase. The enzyme gene is localized to Xq13, but the restriction DNA digestion reaction is not abnormal. The synthesis of heme depends not only on the normal activity of ALA synthase, but also on the normal regulation and delivery of the enzyme to the mitochondria. There are few reports on abnormalities in other steps in heme synthesis, and the individual cases of erythrocytes in the individual cases are free. Increased concentration of porphyrin (FEP) suggests that heme synthase (ie, ferrous chelatase) is defective, but it may also be caused by iron deposition in mitochondria. In a few patients, fecal porphyrin (FEC) increases and FEP decreases significantly. , suggesting that the fecal porphyrin oxidase system is defective, may be a mutation in the mitochondrial gene.
Prevention
Hereditary iron granulocyte anemia prevention
Establish genetic counseling, strict premarital screening, and strengthen prenatal diagnosis to reduce the birth of children.
Complication
Hereditary iron granulocytic anemia complications Complications, diabetes, arrhythmia
In addition to the symptoms and signs of anemia, excessive iron is a common complication of this disease, especially in the advanced stage of the disease, which can lead to death. It is often seen that the liver and spleen are mild to moderately enlarged, liver function is normal or mild abnormal, about One-third of patients develop diabetes, occasionally skin pigmentation, and the most dangerous manifestation of excessive iron is arrhythmia, which often occurs in the late stages of the disease. In addition, excessive iron can cause immune dysfunction, and some uncommon infections such as yeah Enterocolitis and mucormycosis caused by Enteritis can occur in individual cases, and children with severe anemia and growth retardation in children.
Heterozygous and female gene carriers generally do not have anemia, but the morphology of red blood cells is not normal, and patients have no symptoms and signs of pyridoxine deficiency.
Symptom
Hereditary iron granulocyte anemia symptoms common symptoms fatigue
Early symptoms are weak, fatigue, and anemia is moderate, but the difference is very large. Even some relatives have different degrees of anemia. Some members have very poor anemia. They may miss the diagnosis without family investigation.
Examine
Examination of hereditary iron granulocyte anemia
1. Peripheral blood: The degree of anemia varies greatly. Most of the hemoglobin reduction is obvious. The characteristics of hypopigmentation anemia are obvious. The average red blood cell volume (MCV) is mostly reduced, a few are normal, and the individual is increased. The morphology of blood smear is often two-way. You can see two types of cells with normal and abnormal morphology. The red blood cells are obviously uneven in size; the abnormal shape, target shape, oval shape and erythrocyte increase, reticulocytes are normal, occasionally increased, white blood cells and platelets are normal, and red blood cells are infiltrated. Brittleness is obviously inconsistent, and can be increased or decreased.
2. Bone marrow: excessive proliferation of erythroid cells in the bone marrow, iron staining showed a significant increase in hemosiderin, iron granule cells increased to 80% to 90%, and about 10% to 40% of ring-shaped iron granule cells were observed. Most of the latter are middle and late erythrocytes. Iron granules can also be found in blood smears. Occasionally, giant erythrocytes are present, which may be accompanied by folic acid deficiency.
3. Most of the serum iron is increased, and the iron saturation is often significantly increased. The iron kinetics study usually shows that the plasma iron clearance rate is accelerated, which is 1/4 to 1/2 of normal; the iron utilization rate is reduced, about 1/5 of normal. One-third, liver biopsy showed iron deposition, and the liver of non-transfusion patients can have the same changes, often with asymptomatic small nodular cirrhosis, similar to liver lesions of hereditary hemochromatosis.
4. FEP in red blood cells is reduced or normal, and FEC in red blood cells is mostly normal. In cases with ineffective pyridoxine treatment, FEC can be high and FEP is significantly reduced.
The survival time of red blood cells measured by 5.51Cr is normal or slightly shortened, and the average life span of red blood cells is 40 to 100 days.
6. Increased excretion of uric acid (4,8-dihydroxyquinolinic acid) and/or canine quinolinic acid, indicating abnormal metabolism of tryptophan.
Diagnosis
Diagnosis and diagnosis of hereditary iron granulocyte anemia
diagnosis
According to the characteristics of this disease, it is generally not difficult to make a diagnosis of iron granule anemia.
Differential diagnosis
However, it needs to be differentiated from idiopathic and secondary iron granulocyte anemia. Therefore, it must be based on detailed medical history and physical examination, as well as family investigation. In addition, the disease needs to be differentiated from thalassemia, and patients with thalassemia can At the same time, accompanied by anemia of iron granule cells, due to the significant reduction in globin synthesis, excess heme can feedback inhibition of ALA synthase, leading to anemia of iron granulocytes.
