RHAG – Overhydrated Hereditary Stomatocytosis

Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder of erythrocyte volume regulation characterized by transient stomatocytosis and hemolytic anemia. We describe a pediatric patient with beta-thalassemia who presented with severe anemia and up to 50% stomatocytes on peripheral smear. Genetic testing identified a heterozygous missense variant in RHAG, c.194T>C (p.Phe65Ser), confirming the diagnosis of OHSt (PMID:38087905). No additional affected family members were reported, and the stomatocytosis resolved with hemolysis control.

RHAG encodes the Rh50 glycoprotein, essential for Rh‐complex assembly and erythrocyte volume homeostasis. Although functional assays specific to OHSt were not performed, the correlation of variant presence with stomatocyte formation supports a dominant‐negative or gain‐of‐function mechanism. Further mechanistic studies and family segregation analyses are needed to strengthen the association.

Key Take-home: Heterozygous RHAG missense mutations can underlie OHSt and should be considered in patients with unexplained stomatocytosis, guiding appropriate genetic counseling and management.

References

• Journal of clinical laboratory analysis • 2023 • Transient presence of stomatocytes: A clue to the diagnosis of overhydrated hereditary stomatocytosis in a child with beta-thalassemia. PMID:38087905

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