Autosomal Recessive Spherocytosis: A Series of 5 Cases of Compound Heterozygous SPTA1 Mutations

Background

Autosomal recessive (AR) hereditary spherocytosis (HS) is increasingly diagnosed given the improved availability of genetic testing for red cell disorders. Patients with AR HS vary in the severity of their anemia, transfusion needs, response to splenectomy, and complications of disease. Patients may present with severe anemia in-utero or anemia with reticulocytopenia, complicating the differential diagnosis.

Objective

The objective of this abstract is to describe five patients with genetically confirmed AR HS, including their initial presentations, management and complications.

Design/Method

The electronic health records (EHRs) of 5 patients within our institution known to have a diagnosis of AR HS were reviewed for clinical data, laboratory data, genetic testing results, and maternal obstetric data, if available.

Results

All five patients had compound heterozygous pathogenic variants in SPTA1, two of whom were siblings and shared the same mutations. Three patients were male, and all five self-identified as White, Hispanic.

The diagnosis of AR HS was made via whole exome sequencing (n=3) or a commercially available hemolytic anemia next-generation panel (n=1). Known familial variant sequencing was obtained in the fifth patient based on the affected sibling’s results.

All five patients have been transfusion-dependent since birth. Four were diagnosed with anemia in utero, two suffering from hydrops fetalis (HF), with these four requiring intrauterine transfusions. One had no abnormal intrauterine findings but was anemic with severe conjugated hyperbilirubinemia at birth.

Reticulocytopenia was present within the first week of life in all five patients, with two patients initially undergoing workup for suspected red cell aplasia. All remain transfusion-dependent; four additionally receive chelation therapy. Total splenectomy (n=1) and partial splenectomy (n=1) did not eliminate transfusion dependence. Two patients are also followed by nephrology for persistent hypertension, one requiring therapeutic intervention.

Three of the five patients have had magnetic resonance imaging (MRI) for evaluation of iron burden. All three demonstrated significant burden of iron in the liver, and one had an abnormal cardiac T2*.

Conclusion:

We describe a cohort of five patients with AR HS secondary to compound heterozygote SPTA1 mutations. All have remained transfusion-dependent since birth, demonstrating a severe clinical phenotype that may present with fetal anemia. Both hematologists and maternal-fetal-medicine clinicians should consider AR HS in the differential for fetal anemia and non-immune hydrops fetalis.