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Autosomal recessive sideroblastic anemia
Congenital autosomal recessive sideroblastic anemia (ARSA) is a non-syndromic, microcytic/hypochromic sideroblastic anemia, present from early infancy and characterized by severe microcytic anemia, which is not pyridoxine responsive, and increased serum ferritin.
ORPHA:260305Classification level: Disorder
To date, fewer than 30 unrelated genetically characterized individuals with congenital ARSA have been reported in the northern hemisphere.
Congenital ARSA presents in early infancy, within the first weeks or months after birth, and is associated with severe microcytic anemia, increased transferrin saturation and increased serum ferritin. Clinical features are those of anemia and iron overload and include pallor, fatigue, weakness, breathlessness, splenomegaly, hyperglycemia, glucose intolerance and skin hyperpigmentation. Complications of iron overload include heart arrhythmias, heart attacks and liver disease (cirrhosis, cancer). Patients need blood transfusions to survive and do not respond to treatment with pyridoxine (vitamin B6).
ARSA is caused by a homozygous or compound heterozygous mutation in the SLC25A38 gene located on chromosome 3p22.1.
Diagnosis is based on clinical findings together with full blood examination including blood smear and reticulocyte count, measurement of iron stores and bone marrow aspirate showing ringed sideroblasts. Unresponsiveness to pyridoxine treatment often leads to confirming SLC25A38 gene mutation analysis.
Differential diagnosis includes other types of sideroblastic anemia and particularly bears resemblance with X-linked sideroblastic anemia (XLSA, see this term).
In case of family history, prenatal diagnosis by amniocentesis or chorionic villus sampling and cytogenetic analysis is possible, as early diagnosis in a child may be of great benefit for treatment of anemia and avoidance of iron overload, historically the main cause of early death.
The SLC25A38 gene mutation is transmitted as an autosomal recessive trait. Genetic counseling should be offered to affected individuals and their families informing them of the possibilities of carrier testing for at-risk family members and the genetic risk for transmitting it on to their children.
Management and treatment
ARSA differs from X-linked sideroblastic anemias because it is usually more severe and is not responsive to treatment with pyridoxine. Treatment is supportive and involves hematological monitoring, the surveillance of iron levels and nearly always comprises chronic blood transfusions. If iron overload has already developed, iron chelation can be used to normalize iron levels. In some cases, bone marrow transplantation is considered as a successful treatment option.
Prognosis is variable and depends on the severity of microcytic anemia. Quality of life is affected in the case chronic blood transfusions are needed. In well treated patients life expectancy is thought to be normal.
- Guidance for genetic testing
- Français (2019, pdf)