2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Multiple Intestinal Atresia With Combined Immunodeficiency, a New Kid in the Block

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The study discusses a recently identified etiology of multiple intestinal atresia (MIA) with combined immunodeficiency (CID) caused by homozygous PI4KA variants associated with loss of function (LOF) in the same pathway. The study specifically focuses on a cohort of 12 infants in Amish families with a PI4KA variant, one of whom had detailed immuno-profiling. This patient exhibited severe T cell lymphopenia, particularly of CD8+ T cells, moderate B and NK cell lymphopenia, and agammaglobulinemia. The patient's parents opted for palliative care instead of surgical repair.<br /><br />The study highlights the need to consider PI4KA LOF variants in cases of MIA with CID, particularly within the Amish population. It also notes that this is the most complete immune characterization reported to date on a patient with this variant. The management of MIA with CID is complex and may involve high risks of morbidity and mortality. Therefore, the study suggests that thorough discussions regarding goals of care and expected outcomes should be considered.<br /><br />The patient in the case study was a former 35+6 week girl with congenital bowel obstruction. Surgical correction was performed, but multiple portions of her intestine had to be resected. She was found to have low T cell receptor excision circles (TRECs) counts, low CD3+ T cells (particularly CD8+ T cells), low CD4+ T cells, normal NK and B cells, and normal serum IgG. Genetic testing revealed homozygosity for the NM_058004.4:c.4867T>G; p.(Tyr1623Asp) variant in PI4KA. However, the family opted for palliative care, and the patient died at home at one month of age.<br /><br />In conclusion, this study sheds light on the association between homozygous PI4KA variants and MIA with CID. It emphasizes the importance of considering this variant in the diagnosis of MIA with CID, particularly within the Amish population. The study also highlights the complexities of management and the need for thorough discussions with families regarding goals of care and expected outcomes.

Asset Subtitle

Presenting Author - Jessica T. Ogawa, MD; Co-Author - Sulin Wu; Co-Author - Vincent Cruz, MD, MS; Co-Author - Joao Pedro Lopes, MD;

Meta Tag

Clinical History

Congenital Anomaly

Gastrointestinal System

Genetic Testing

Co-Author Sulin Wu

Co-Author Vincent Cruz, MD, MS

Co-Author Joao Pedro Lopes, MD

Presenting Author Jessica T. Ogawa, MD

Keywords

multiple intestinal atresia

combined immunodeficiency

PI4KA variants

Amish families

T cell lymphopenia

palliative care

MIA with CID

congenital bowel obstruction

genetic testing

goals of care