Clinical Guidance

G6PC3 deficiency is highly variable in its severity and associated clinical features. Individuals with "nonsyndromic" disease have only severe congenital neutropenia. The majority of persons with G6PC3 deficiency have cardiovascular and/or urogenital features (so-called classic G6PC3 deficiency). Of those with classic disease, a subset are more severely affected (so-called Dursun syndrome) because of the additional involvement of myeloid cells, primary pulmonary hypertension developing in the newborn period, and minor dysmorphic features. While it is estimated that nearly 10% of G6CP3 deficiency is the nonsyndromic form, this could be an underestimate due to ascertainment bias (i.e., selection of more severe phenotypes for testing of G6PC3 in previous studies) .

Diagnostic Criteria

Consensus diagnostic criteria for G6PC3 deficiency have not been established.

Suggestive Findings

G6PC3 deficiency should be suspected in individuals with the following:

• Severe congenital neutropenia defined as an absolute neutrophil count 0.5 x 109/L which usually results in early-onset, frequent, severe bacterial infections

Note: Although maturation arrest of myeloid cells was initially thought to be the typical finding on bone marrow examination , subsequent reports identified bone marrows that were hypercellular and normocellular . More recently, sequential bone marrow examinations have typically revealed normal maturation and only rarely arrested maturation .

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with G6PC3 deficiency, the following evaluations are recommended:

• Full blood count to look for evidence of other hematologic involvement (i.e., intermittent thrombocytopenia and/or lymphopenia)

Surveillance Guidelines

The following are appropriate:

• Frequent follow up by a hematologist or immunologist to monitor infection frequency and neutrophil counts to ensure an adequate response to G-CSF (i.e., absolute neutrophil counts above 0.5x109/L)

• Monitoring of growth in children and pubertal development in adolescents