Diagnosing Congenital Neutropenia

Laura Joszt

Most cases of neutropenia are acquired due to treatment, but there are also congenital neutropenias, which encompass a family of neutropenic disorders.

Physicians caring for patients with severe congenital neutropenia should be ready to detect issues with multiple systems in the body, explained Seth Corey, MD, of the Virginia Commonwealth University and the Massey Cancer Center & Children's Hospital of Richmond, during a session at the 59th American Society of Hematology Annual Meeting and Exposition in Atlanta, Georgia.

He provided the example of how the pancreas is involved in Shwachman–Diamond syndrome, in which the bone marrow malfunctions and some or all types of white blood cells are not created.

“When you have a patient with severe chronic neutropenia, one should look at the eyes, heart, skin, bone, the nervous system…” Corey said.

Individuals with severe congenital neutropenia have a shortage of neutrophils and are prone to recurrent infections. According to Corey, as much as 30% of severe congenital neutropenia is unclassified.

Corey also provided a new workup approach. The current approach begins with a history of onset of neutropenia, documentation, review of past and present infections, family history, and diet. There should also be a physical examination of sites of infection and an exam of skeletal anomalies. A second tier of evaluation includes a bone marrow aspiration and biopsy and blood counts twice a week. Then individuals will typically send off for gene sequencing.

However, Corey introduced a potential third-tier workup. When considering the cost of multiple visits and blood counts, just sending off for gene sequencing may be more cost effective. The third tier is robust next-generation sequencing (NGS) panels to get an idea of the number of different conditions. The cost of NGS panels can be about $2000 at a flat rate, but can be as much as $4000 with a turnover time of 4 to 6 weeks.

“But next generation sequencing is not going to solve everything,” Corey said.

A Canadian study looked at a panel of 72 genes in individuals with known inherited bone marrow failure syndrome, and they were only able to come up with the genetic cause in about 60%. In patients with suspected inherited bone marrow failure syndrome, the success rate was only about 20%, he said.

Corey concluded by summarizing that congenital neutropenias are a “perplexing group of conditions” and that physicians have to go through a thought process to diagnose and treat them.
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