Compound Heterozygosity for Hb Port Phillip and the -α3.7 Deletion Leads to Persistent Hypoxemia in a Chinese Pediatric Family.

Hemoglobin variants and α-thalassemia deletions are uncommon causes of unexplained hypoxemia in children. This study reports a Chinese family affected by compound heterozygous HBA2 mutations that decrease hemoglobin-oxygen affinity. Clinical data, oxygen saturation (SpO2) trends, chest imaging, capillary hemoglobin electrophoresis, and genetic testing were conducted on the proband and his family members. The proband had persistently low SpO2 after pneumonia resolution, without respiratory distress; his 4-year-old brother experienced similar hypoxemia with normal cardiopulmonary evaluations. Capillary electrophoresis showed increased variant hemoglobin fractions in both siblings and their mother. Genetic analysis revealed compound heterozygosity: a maternally inherited HBA2: c.275T > C (p.L92P, Hb Port Phillip) and a paternally inherited -α3.7 deletion. The proband's mother is heterozygous for the point mutation and asymptomatic, while the father carries the -α3.7 deletion. This is the first report of a compound heterozygote for Hb Port Phillip and -α3.7 deletion with hypoxemia in a Chinese family, thus broadening the phenotype-genotype spectrum of hemoglobinopathies. The unexpected low oxygen saturation may result from a hemoglobin variant in the setting of mild microcytic anemia; hemoglobin electrophoresis and genetic testing are crucial for accurate diagnosis and can prevent unnecessary interventions.