Syndromic congenital sideroblastic anaemias (CSA) are a heterogeneous group of anaemic syndromes characterized by the presence of anaemia together with other clinical syndromes. These different entities are due to mutations of nuclear genes or mutations in the mitochondrial DNA. Sideroblastic Anaemia with ataxia (XLSA/A) is an autosomal recessive sideroblastic anaemia due to mutations of the ABCB7 gene.
Syndromic CSA is a heterogeneous group of rare genetic disease causes by mutations in different genes or in the mitochondrial DNA. Sideroblastic Anaemia with ataxia (XLSA/A) is a autosomal recessive sideroblastic anaemia due to mutations of the ABCB7 gene. ABCB7 gene encodes an essential component of the iron sulphur (Fe/S) cluster machinery, locates in the inner mitochondrial membrane and involved in transport of Fe/S clusters to cytosol. The ABCB7 function is essential for erythroid cells and central nervous system. So far only three families (10 subjects) have been described with this syndrome. It is estimated that the prevalence of this diseases is <1 / 1 000 000.
Deficiency of the mitochondrial ABCB7 transporter causes mild-moderate hypochromic, microcytic anaemia with non-progressive cerebellar ataxia manifest in infancy or early childhood. There is no systemic iron-overload reported for this disease. The typical neurological abnormalities include non-progressive cerebellar ataxia, diminished deep tendon reflexes, and lack of co-ordination.
No means of early detection or prevention of XLSA/A are known. Anaemia is not responsive to pyridoxine treatment, but normally anaemia is not severe enough to require repeated blood transfusion. Patients with neurological abnormalities may require special care in upbringing and education.
ABCB7-related syndromic CSA is an autosomal recessive disease. An individual can be heterozygous for the disorder (healthy carrier) when only one of the ABCB7 allele is mutated, or homozygous or compound heterozygous (affected individual) when two ABCB7 alleles are mutated. A couple who carries each one a mutated ABCB7 allele have a 25 percent risk of having a child affected by the disorder at each pregnancy. The risk of having a child who is a healthy carrier of the disorder is 50 percent at each pregnancy, and the risk that a child will not have the disorder and will not be a carrier is 25 percent. Ask for genetic counselling to get a complete explanation.