Q:

7/9/2019
A five year-old ex 36 weeker with hx of gastroschisis and six month NICU stay found to have lymphopenia on routine blood work by her pediatrician one year ago. Lymphocyte subset one year ago were CD3 (#350), CD4 (#182), CD8 (#108), normal B and NK cell. Follow up Lym subset in May 2019 were CD3 (#195), CD4(#86), CD8(#59), normal B and NK. Invitae PID panel showed no known genetic defect for PID.

T cell subsets at Mayo lab in 5/19: CD4CD45RA (46%, #38), CD4CD45RO (54%, #44), CD8CD45RA (91%, #53), CD8CD45RO (8%, #5). TREC study at Mayo lab in 6/19: CD3 (#244, 865-3618), CD4 (#121, 497-2267), CD8 (#79, 243-1303). CD4 RTE at Mayo lab in 6/19: CD4 absolute (#139, 582-1630), CD4 RTE % (25.7, 25.8-68), CD4 RTE absolute (#36, 170-1007). This result is consistent with decreased thymic output. Immunoglobulin levels showed normal IgG and IgA with low IgM. PHA study in 8/18 was low response but repeated PHA, ConA and PMW in 5/19 showed normal response. Clinically the patient has been well without having bacterial or opportunity infections, normal growth for height and weight. The patient received MMR vaccine at age of 4 without developing any reaction.

HIV study was negative. No chronic diseases. GI consult was normal. What is the next step for T-cell lymphopenia (likely thymic output problem so far) and management?

A:

I asked Dr. Kathleen Sullivan to provide input. Her response is as follows:

"Gastroschisis has been described as associated with low TRECs. So it may just be that the disrupted development of the abdominal wall is enough to re-route lymphatic circulation. Having said that, I would be worried about a five year old with such persistently low T cells. Not enough to start a BMT discussion, but definitely worried. To start, I would be sure that there is no micro deletion - these are not reliably picked up by WES. A SNP array is not perfect but the best technology at the moment for this. I would also ask genetics to take a look and be sure there are no other features to make them think this is part of a larger syndrome. Gastroschisis is usually isolated but not always.

Can you get the exact results of the newborn TREC screen? It would help you to determine if this is acute or the child has always had it. Similarly can you look back at the NICU CBC for the lymphocyte counts? If the lymphopenia has been there forever then thymus hypoplasia is the most likely cause and you don’t have many options at the moment. If the child had great ALCs and a stone cold normal TREC then you need to figure out where the lymphocytes have gone. Intestinal loss is a good bet in this scenario.

Management: I would continue to watch closely. With such profound lymphopenia- regardless of the cause- risks of allergy, autoimmunity and opportunistic infections are high."

I trust this will be helpful to you and your patient.

Regards,
Daniel J. Jackson, MD, FAAAAI

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