Patient cases
Male, 2 years of age. Presented for 6 months due to persistent cough and worsening of pallor and drowsiness. The birth history is an emergency cesarean section at 41 weeks of pregnancy due to fetal distress, followed by healthy growth. Liver and spleen enlargement were not seen on physical examination, and the height and weight of the children were lower than normal age in the 2nd and 4th percentiles, respectively.
Laboratory tests
Complete blood count showed haemoglobin (Hb) 27 g/L, mean erythrocyte volume (MCV) 48 fl, mean hemoglobin (MCH) 135 pg, reticulocytes 0.4×109/L, white blood cell count 6.62 ×109/L, neutrophil count 2.23×109/L, ferritin 262 μg/L.
Peripheral blood smears show two forms of erythrocytes, one normal RBCs and the other distinctly heterogeneous RBCs, target cells, irregular, and fragmented RBCs (Figure 1). Despite the presence of 2 erythrocyte morphologies, clinical manifestations suggest hereditary Epolysin's xenocythrocytosis.
(Figure 1)
Eosin-5'-maleimide (EMA) binding test is normal, and hemolysis test is screened negative (bilirubin 6 μmol/L, lactate dehydrogenase 214 iu/L).
Bone marrow aspiration biopsy shows normal erythropoiesis, Perls staining (Figure 2) shows iron storage, and occasionally ring iron larocytes make up less than 1% of all iron larocytes.
(Figure 2)
The child's hemoglobin, erythrocyte index, and EMA binding tests were normal, and the mother's blood smear occasionally showed oval red blood cells, and others were normal. Further investigation of the child's family history revealed that the child's maternal cousin had congenital tecoplasmic anemia.
Targeted genetic analysis revealed an abnormal combination of genes, with nucleotide replacement CA (c.791 C>A) in exon 7 of the ALAS2 gene in children, although there were no previous reports, predicting that the amino acid serine was replaced by tyrosine at the residual 264 (p.ser264Tyr) site, considering maternally inherited X-linked ferrulocyte larval anemia. In addition, the child was heterozygous SPTA1 (c.2608G>A; p.Val870Met) and SPTB (c.2519G>A; p.Arg840His) variant.
This dual genetic effect is thought to be possible in line with hereditary Philonin xenocythemia. The child's mother is a SPTA1 mutation carrier with oval red blood cells, suggesting anthroposis.
At this stage, the child's main phenotypic abnormalities are unclear and he or she is initiated experimental treatment with pyridoxine due to his family history of congenital ferric juvenile anemia and potentially pathogenic ALAS2 gene mutations. Its hemoglobin level rises significantly to 112 g/L, and no further red blood cell transfusion is required for 3 months.
Despite the absence of significant ferritocyte changes in children, the initial diagnosis is pyridoxine-sensitive X-linked hemophilia. Mutations speculated to be associated with erythrocyte membrane abnormalities may lead to the appearance of these morphological abnormalities, with the child not significantly hemolysis, and the two forms of blood smears inconsistent with significant pathological erythrocyte membrane abnormalities (e.g., hereditary peloponin xenocythrocytosis).
This example emphasizes the importance of the correlation between genetic and phenotypic features in the diagnosis of congenital anemia, the absence of obvious ring ferroblasts does not exclude the diagnosis of congenital ferroblastic anemia, a complete family history and appropriate genetic analysis are particularly important in the management of the child in this case.
【Reference Source】
Thomas Creasey,Tina Biss.et al. Pyridoxine-sensitive X-linked ‘sideroblastic’ anaemia in the absence of ring sideroblasts – molecular diagnosis. British Journal of Haematology, 2018, 180, 10.
Source: Medical Pulse Hematology
Editor: Ren Mileage Reviewer: Xiao Ran