X-linked sideroblastic anaemia, pyridoxine-responsive
X-linked sideroblastic anaemia is a generally microcytic, hypochromic anaemia of varying severity thatpresent at any age from Birth to the 9th decade and that may respond to treatment with pyridoxine and Folic acid. Female carriers are usually unaffected, however, one quarter of probands are Female and almost half of the Female probands have macrocytic rather than microcytic red Blood cells.
Additional InformationX-linked sideroblastic anaemia is generally a microcytic, hypochromic anaemia of varying severity that may respond to treatment with pyridoxine and Folic acid. It is a rare disorder with only 100-200 cases and fewer than 100 unrelated probands described in the literature. The anaemia can present at any age from Birth to the 9th decade. It is associated with erythroblast Mitochondrial iron overload and the appearance of ring sideroblasts After iron staining of bone Marrow smears. Increased ineffective and expanded erythropoiesis leads to increased absorption of Dietary iron and a risk of Iron overload. Symptoms are those of anaemia or Iron overload such as weakness, breathlessness, splenomegaly, Cardiac problems, pallor, fatigue, abnormal liver function, hyperglycaemia, glucose Intolerance and Skin hyperpigmentation. Some patients have no symptoms and are detected incidentally by haematological Screening or through Family study. The causes are the inheritance or de novo occurrence of mutations in the Gene encoding the erythroid form of delta Amino levulinic acid synthase (ALAS2) on the short Arm of the X chromosome. Female carriers are usually unaffected, however, one quarter of probands are Female who have X-chromosome inactivation skewed against the unaffected allele and almost half of the Female probands have macrocytic rather than microcytic red blood Cells due to the heterozygous inheritance of a severe/ allele. Diagnosis requires a full Blood and reticulocyte count, measurement of Iron stores, exclusion of thalassaemia as a cause, bone Marrow biopsy, and mutation analysis of the ALAS2 gene. The differential Diagnosis should include other types of sideroblastic anaemia (see these terms). Most Female carriers show some evidence of microcytic, hypochromic red blood Cells but haematological parameters cannot be relied upon for Genetic counselling purposes and DNA analysis is required. Prenatal Diagnosis is rarely indicated or requested, however, early Diagnosis in a child may be of great benefit for treatment of anaemia and avoidance of Iron overload, the main cause of early Death in the past. Treatment is supportive and involves haematological monitoring, the surveillance of Iron levels, lifetime pyridoxine supplementation in those who respond haematologically and Folic Acid supplementation. Pyridoxine response varies in degree and is rarely complete. Prophylactic occasional phlebotomy can be performed to Prevent iron overload. If Iron overload has already developed, phlebotomy, Iron chelation or a combination of the two can be used to reduce Iron levels to normal and may simultaneously increase the haemoglobin level. Blood transfusions may be needed on occasion but are only required on a regular basis for those most severely affected. Prognosis is variable but for patients with pyridoxine-responsive anaemia whose Iron stores are kept low, normal life expectancy should be achievable.
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