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

Xia Huang; Hua Jiang; Hua Ren; Xia Huang; Hua Jiang; Hua Ren

doi:10.3934/Allergy.2025014

AIMS Allergy and Immunology

2025, Volume 9, Issue 3: 180-189. doi: 10.3934/Allergy.2025014

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Case report

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

Department of Pediatrics, Yanan University Affiliated Hospital, Yan'an 716000, China

Received: 28 July 2025 Revised: 07 September 2025 Accepted: 11 September 2025 Published: 19 September 2025

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.
- ATAD3A gene,
- Harel-Yoon syndrome (HAYOS)
Citation: Xia Huang, Hua Jiang, Hua Ren. A case report of Harel-Yoon syndrome associated with ATAD3A gene variants[J]. AIMS Allergy and Immunology, 2025, 9(3): 180-189. doi: 10.3934/Allergy.2025014

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Abstract

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.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author contributions

Xia Huang was responsible for patient admission, physical examinations, and ancillary examinations; she also drafted the initial manuscript. Hua Jiang conducted the data analysis and results interpretation; he assisted in data collation. Hua Ren designed the research framework, critically reviewed the entire manuscript, assisted in manuscript submission, and oversaw the study integrity.

Ethics approval of research

This research has received ethical approval from the Ethics Commission of Yanan University Affiliated Hospital (IIT-R-20250154). Written informed consent was obtained from the patient.

References

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