High-performance liquid chromatography screening reveals HbS/β+-thalassemia double heterozygosity as a pediatric muscular dystrophy mimic.

INTRODUCTION

Compound hemoglobinopathies may present with variable clinical phenotypes, particularly when additional genetic modifiers coexist. Sickle cell hemoglobin (HbS)/β+-thalassemia can mimic other pediatric conditions, potentially delaying diagnosis. High-performance liquid chromatography (HPLC) is a widely accessible first-line screening tool that can facilitate identification of HbS/β+-thalassemia.

METHODS

An 8-year-old boy from Mali presented with recurrent severe lower limb pain and gait impairment, initially suggesting a neuromuscular disorder. Laboratory evaluation revealed severe microcytic hypochromic anemia (hemoglobin, 6.3 g/dL) with reticulocytosis and biochemical evidence of hemolysis, despite preserved iron stores. Creatine kinase levels were normal. Peripheral smear showed anisopoikilocytosis with target cells, basophilic stippling, and rare sickled erythrocytes.

RESULTS

The HPLC findings demonstrated HbS predominance (64.2%) with elevated fetal hemoglobin (8.1%), increased adult hemoglobin A2 (5.4%), and residual adult hemoglobin A (22.3%), consistent with HbS/β+-thalassemia. Molecular testing confirmed heterozygous HbS and β+-thalassemia variants, homozygous 3.7-kilobase α-globin gene deletion, and a pathogenic glucose-6-phosphate dehydrogenase A‒ haplotype. Positive parvovirus B19 immunoglobulin M suggested an additional acute trigger.

DISCUSSION: Routine hematologic parameters combined with HPLC screening can promptly identify complex hemoglobinopathies in clinically misleading presentations, enabling accurate diagnosis, appropriate management, and genetic counseling.