Sidroblastic anemia

Sidroblastic anemias are a various group of erythropoietic disorders in which iron deposits in erythroblast mitochondria and lead to different abnormality in heme synthesis and mitochondrial function. These iron-filled mitochondria bordering the nucleus of red blood cell and give the ring shape under the microscope.  It can be classified in to congenital and acquired forms and both types have distinct causes, treatment and prognoses.

Panel test:

Genetics test:

·         ALAS2 – X-linked sideroblastic anemia (XLSA)

·         SLC25A38, HSPA9, and GLRX5 (Autosomal recessive nonsyndromic sideroblastic anemias)

·         ABCB7 – XLSA with ataxia (XLSA/A)

·         NDUFB11 – X-linked sideroblastic anemia with variable syndromic features such as short stature, developmental delay or myopathy

·         TRNT1 – Sideroblastic anemia with immunodeficiency, periodic fevers, and developmental delay (SIFD)

·         PUS1, YARS2, NDUFB11, MT-ATP6, and LARS2 – Myopathy, acidosis, and sideroblastic anemia (MLASA) and MLASA variants

·         SLC19A2 – Thiamine-responsive megaloblastic anemia (TRMA)

·         FECH – Erythropoietic protoporphyria (EPP)

·         Mitochondrial DNA deletions and rearrangements – Pearson marrow-pancreas syndrome

In the MDS disorders with ring sideroblasts, acquired mutations in two genes are very common:

·         SF3B1 – All three MDS/MPN disorders with ring sideroblasts

·         JAK2 V617F mutation – MPN with ring sideroblasts and thrombocytosis

Lab tests:

CBC with Platelet Count and Automated Differential

Reticulocytes, Percent and Number

Blood Smear with Interpretation

Bone marrow examination (for ring sideroblasts)

Iron and Iron Binding Capacity

Ferritin

Vitamin B12

Hemoglobin Electrophoresis

Soluble transferrin Receptor

Erythrocyte Porphyrin (EP)

References:

1.      Bergmann AK, Campagna DR, McLoughlin EM, et al. Systematic molecular genetic analysis of congenital sideroblastic anemia: evidence for genetic heterogeneity and identification of novel mutations. Pediatr Blood Cancer 2010; 54:273.

2.      Liu G, Guo S, Kang H, et al. Mutation spectrum in Chinese patients affected by congenital sideroblastic anemia and a search for a genotype-phenotype relationship. Haematologica 2013; 98:e158.

3.      Ducamp S, Kannengiesser C, Touati M, et al. Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations. Hum Mutat 2011; 32:590.

4.      Bottomley SS. Sideroblastic anemias. In: Wintrobe’s Clinical Hematology, 13th ed, Greer JP, Arber DA, Glader B, et al. (Eds), Lippincott, Williams and Wilkins, Philadelphia 2014. p.643.