A case report of Harel-Yoon syndrome associated with ATAD3A gene variants

In this study, we reported a rare case of Harel-Yoon syndrome (HAYOS) caused by a mutation in the ATAD3A gene on chromosome 1p36.33. A 34-day-old female infant presented with the chief complaints of “intermittent irritability and poor feeding for 8 days, worsening over the past hour.” Laboratory investigations revealed hyperammonemia and lactic acidosis. Cardiac injury biomarkers and inflammatory markers were elevated. Echocardiography indicated cardiac insufficiency and cardiomyopathy. Both parents were phenotypically normal, non-consanguineous, and had no family history of inherited disorders. Further whole-exome sequencing (including mitochondrial DNA) identified a heterozygous missense variant, c.1582C>T (p.Arg528Trp), in the ATAD3A gene in the proband. This was confirmed to be a de novo variant, leading to a diagnosis of HAYOS. This variant was classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines and constitutes the genetic etiology of HAYOS in this patient. We summarized the clinical characteristics of this case and reviewed the relevant literature. This report expands the known genotype-phenotype spectrum associated with ATAD3A gene variants and enhances clinical recognition and diagnostic capabilities for this rare disorder.