Association of HAX1 Deficiency with Neurological Disorder

Abstract

Severe congenital neutropenia (SCN) is a rare, heterogeneous, primary immunodeficiency disorder characterized by early onset of severe bacterial infections. We here describe a case of SCN associating neutropenia and neurodevelopmental delay. The girl was well until the age of 9 months, when she suffered from an episode of convulsion. Subsequently, she developed several episodes of superficial abscesses, oral ulcers and otitis media. Further work-up revealed severe congenital neutropenia caused by a homozygous mutation (R86X) in the antiapoptotic molecule HAX1. She also suffered from psychomotor retardation and recurrent seizures. This case illustrates that HAX1 deficiency may be associated with a neurological phenotype.

Key words

convulsion - developmental delay - HAX1 - mutation - neurological disorder - severe congenital neutropenia

References

• 1 Ancliff PJ, Gale RE, Liesner R, Hann IM, Linch DC. Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease.  Blood. 2001;  98 2645-2650
• 2 Carlsson G, Fasth A. Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original “Kostmann family” and a review.  Acta Paediatr. 2001;  90 757-764
• 3 Dale DC, Person RE, Bolyard AA, Aprikyan AG, Bos C, Bonilla MA. et al . Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia.  Blood. 2000;  96 2317-2322
• 4 Hippe A, Bylaite M, Chen M, Mikecz A von, Wolf R, Ruzicka T. et al . Expression and tissue distribution of mouse Hax1.  Gene. 2006;  379 116-126
• 5 Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer AA. et al . HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease).  Nat Genet. 2007;  39 86-92
• 6 Mandemakers W, Morais VA, Strooper B De. A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases.  J Cell Sci. 2007;  120 1707-1716
• 7 Rezaei N, Farhoudi A, Pourpak Z, Aghamohammadi A, Moin M, Movahedi M. et al . Neutropenia in Iranian patients with primary immunodeficiency disorders.  Haematologica. 2005;  90 554-556
• 8 Rezaei N, Farhoudi A, Ramyar A, Pourpak Z, Aghamohammadi A, Mohammadpour B. et al . Congenital neutropenia and primary immunodeficiency disorders: a survey of 26 Iranian patients.  J Pediatr Hematol Oncol. 2005;  27 351-356
• 9 Rezaei N, Moin M, Pourpak Z, Ramyar A, Izadyar M, Chavoshzadeh Z. et al . The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia.  J Clin Immunol. 2007;  27 525-533
• 10 Welte K, Zeidler C, Dale DC. Severe congenital neutropenia.  Semin Hematol. 2006;  43 189-195

Correspondence