2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Not All Severe Combined Immunodeficiency Patients are Created Equal and When Rapid Genetic Testing Matters

Not All Severe Combined Immunodeficiency Patients are Created Equal and When Rapid Genetic Testing Matters

Pdf Summary

Severe combined immunodeficiency (SCID) is a rare genetic disorder that affects T cell development and can be life-threatening. A 7-day-old infant presented with severe leukopenia, thrombocytopenia, and septic shock, raising suspicion of a rare form of SCID called reticular dysgenesis. Rapid genetic testing was performed using whole exome sequencing, which revealed a homozygous genetic variant in the AK2 gene, confirming the diagnosis of reticular dysgenesis. This disorder is characterized by low neutrophil counts, lymphopenia, and a unique infectious pattern, often presenting within the first week of life. The only curative treatment for reticular dysgenesis is hematopoietic stem cell transplantation (HSCT). Early diagnosis is crucial for successful HSCT and long-term survival. The AK2 gene encodes the adenylate kinase 2 enzyme, which plays a role in regulating mitochondrial adenine nucleotide levels and energy production in cells. The molecular pathophysiology of AK2 deficiency in reticular dysgenesis is not fully understood. This case emphasizes the importance of thorough phenotyping and recognizing atypical presentations of SCID. The coordination and collaboration of multiple medical teams, including ICU, immunology, hematology-oncology, genetics, and infectious disease, were necessary to provide a timely and accurate diagnosis for effective treatment.

Asset Subtitle

Presenting Author - Moon Ley Tung, MBBS, MRCP (UK), FRCPath (Hematology)(UK); Co-Author - Karin Panzer, MS, CGC; Co-Author - Nicole Safina, MD,FAAP, FACMG; Co-Author - Alpa Sidhu, MBBS, PhD;

Meta Tag

Etiology

Genetic Testing

Genotype-Phenotype Correlations

NextGen Sequencing

Transplantation

Co-Author Karin Panzer, MS, CGC

Co-Author Nicole Safina, MD,FAAP, FACMG

Co-Author Alpa Sidhu, MBBS, PhD

Presenting Author Moon Ley Tung, MBBS, MRCP (UK), FRCPath (Hematology)(UK)

Keywords

Severe combined immunodeficiency

SCID

reticular dysgenesis

genetic disorder

AK2 gene

diagnosis

hematopoietic stem cell transplantation

neutrophil counts

lymphopenia

mitochondrial adenine nucleotide levels