Neutrophil-specific granule deficiency

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Neutrophil-specific granule deficiency
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Synonyms SGD
Pronounce
Field N/A
Symptoms Recurrent bacterial infections, particularly of the skin and respiratory system, due to impaired immune response.
Complications Chronic infections, delayed wound healing, development of granulomatous inflammation, potentially leading to organ damage.
Onset N/A
Duration Lifelong
Types There is one primary type of neutrophil-specific granule deficiency, which is congenital.
Causes Caused by mutations in the **CSF3R** gene, leading to impaired granulocyte maturation and function.
Risks Inherited in an autosomal dominant pattern, but some cases can be sporadic due to de novo mutations.
Diagnosis Diagnosed through blood tests showing a reduced number of neutrophil-specific granules, typically using flow cytometry, electron microscopy, or genetic testing for CSF3R mutations.
Differential diagnosis Differentiated from other causes of recurrent infections, such as chronic granulomatous disease (CGD), myeloperoxidase deficiency, and other neutrophil dysfunctions.
Prevention No known prevention, as the condition is genetic. Early diagnosis and management can prevent complications.
Treatment Supportive treatment for infections with antibiotics, granulocyte colony-stimulating factor (G-CSF) to stimulate neutrophil production, and potential bone marrow transplant in severe cases.
Medication G-CSF (Granulocyte Colony-Stimulating Factor) to help stimulate neutrophil production and manage infections.
Prognosis With early detection and appropriate treatment, many individuals can live normal lifespans; however, recurrent infections and complications can lead to reduced quality of life in severe cases.
Frequency Rare; exact incidence is not well-defined.
Deaths Mortality is rare but can occur due to complications from infections or severe inflammation, particularly in untreated cases.


Neutrophil-specific granule deficiency ( previously known as lactoferrin deficiency) is a rare congenital immunodeficiency characterized by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils.

Epidemiology[edit | edit source]

Estimation of the frequency of SGD is difficult, as it is an extremely rare disease with few cases reported in literature. The condition was first reported in 1980, and since only a handful more cases have been published.

Symptoms[edit | edit source]

Atypical infections are the key clinical manifestation of SGD. Within the first few years of life, patients will experience repeated pyogenic infections by species such as Staphylococcus aureus, Pseudomonas aeruginosa or other Enterobacteriaceae, and Candida albicans. Cutaneous ulcers or abscesses and pneumonia and chronic lung disease are common. Patients may also develop sepsis, mastoiditis, otitis media, and lymphadenopathy. Infants may present with vomiting, diarrhea, and failure to thrive.

Diagnosis[edit | edit source]

Diagnosis can be made based upon CEBPE gene mutation or a pathognomonic finding of a blood smear showing lack of specific granules. Neutrophils and eosinophils will contain hyposegmented nuclei (a pseudo-Pelger–Huet anomaly).

Genetics[edit | edit source]

A majority of patients with SGD have been found to have mutations in the CEBPE (CCAAT/enhancer-binding protein epsilon) gene, a transcription factor primarily active in myeloid cells. Almost all patients have been found to be homozygous for the mutation, suggesting the disease is autosomal recessive. One patient, heterozygous for the mutation, was found to be deficient in GFI1, a related gene.

Pathophysiology[edit | edit source]

The defect in CEBPE appears to block the ability of neutrophils to mature past the promyelocyte stage in bone marrow. Since specific (secondary) and gelatinase (tertiary) granules are only produced past the promyelocyte stage of development, these are deficient in SGD. Lactoferrin is the major enzyme found in specific granules, and will be largely absent in the granulocytes of these patients, along with defensins (despite these also being found in azurophilic (primary) granules).

Treatment[edit | edit source]

Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.

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