Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) is characterized by a selective decrease in circulating neutrophils, bone marrow maturation arrest at the promyelocyte stage, and occurrence of infections. Typical infections include omphalitis, pneumonia, sinusitis and gingivitis caused by resident bacteria of the skin, mouth, and oropharynx. While all types of severe congenital neutropenia are sometimes called Kostmann disease, the extended family actually described in detail by Kostmann had a recessive disorder now known to be caused by mutations in HAX1. A recent observation is that some, but not all, HAX1 mutations are associated with neurological disorders. Mutations in HAX1 are not known to cause any type of cyclic or periodic neutropenia.

Tests Available

Forms and Documents

Test Details

HAX1
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

303
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 288 Diseases of white blood cells Excludes: leukemia (204.0-208.9)
* For price inquiries please email zebras@genedx.com

References

  1. Smith BN, et al, Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. Br J Haematol 144:762, 2009
  2. Carlsson G, et al, Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1mutations, J Int Med 264:388, 2008
  3. Germeshausen M, et al. Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype correlations, Blood 111:4954, 2008
  4. Matsubara K, et. al, Severe developmental delay and epilepsy in a Japanese patient with severe congenital neutropenia due to HAX1 deficiency, Haematologica 92(12):e123-5, 2007
  5. Klein C., et al, HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease), Nature Genetics 39:86-90, 2007
  6. Kostmann, R. Infantile genetic agranulocytosis (Agranulocytosis infantilis hereditaria): a new recessive lethal disease in man, Acta Paediatr. 45 (suppl) 1-78. 1956

Forms and Documents

Test Details

ELANE (ELA2)
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

105
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Bellanne-Chantelot, C, Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Registry, Blood 103: 4119-4125, 2004.
  2. Horwitz, M., Mutations in ELA2, encoding neutrophil elastase, define a 210day biological clock in cyclic haematopoiesis, Nat. Gen. 23:433-436, 1999.
  3. Dale et al, Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia, Blood 96: 2317-2322, 2000