[Late diagnosis of WHIM sydrome]. / Diagnóstico tardío de síndrome WHIM.

WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.

Diagnóstico tardío de síndrome WHIM / Late diagnosis of WHIM sydrome

El síndrome WHIM es una inmunodeficiencia primaria de herencia autosómica dominante, debida a mutaciones en el gen CXCR4, que se caracteriza por verrugas cutáneo-mucosas, hipogammaglobulinemia, infecciones bacterianas recurrentes y mielocatesis. El tratamiento se basa en el uso de antibióticos profilácticos, gammaglobulina en dosis sustitutiva y factores estimulantes de colonias de granulocitos o de granulocitos y macrófagos, en forma crónica. Presentamos el caso de una mujer de 21 años que comenzó a los 10 meses de edad con leucopenia y al siguiente año múltiples infecciones con hipogammaglobulinemia requiriendo gammaglobulina endovenosa durante los episodios. Evolucionó con neutropenia crónica. Una punción aspiración de médula ósea mostró la serie mieloide aumentada con ligero predominio de elementos inmaduros. El cuadro fue interpretado como inmunodeficiencia común variable debido a la asociación de múltiples cuadros infecciosos, niveles disminuidos de IgG, IgM e IgA y linfopenia con disminución de linfocitos B de memoria, por lo que comenzó tratamiento sustitutivo con gammaglobulina endovenosa más antibióticos profilácticos. A los 20 años se registraron pequeñas verrugas en manos que progresaron hacia antebrazos, abdomen, cara y rodillas. Se realizaron estudios moleculares para la búsqueda de mutaciones en el gen CXCR4 donde se detectó la mutación p.Arg334STOP en estado heterocigota confirmando el diagnóstico de síndrome WHIM, que es una inmunodeficiencia infrecuente y de difícil diagnóstico.

WHIM syndrome is a primary autosomal dominant immuno deficiency due to CXCR4 mutations characterized by mucocutaneous warts, hypogammaglobulinemia, recurrent bacterial infections and myelokathesis. Treatment consists in prophylactic antibiotics, immunoglobulin replacement and granulocyte or granulocyte/monocyte colony stimulating factors. We present the case of a 21 year old woman who showed leukopenia at 10 months of age and one year later multiple infections with hypogammaglobulinemia requiring intravenous immunoglobulin. During follow up she developed chronic neutropenia. A bone marrow aspiration showed increased myeloid series with predominance of immature elements. On the basis of infections, low levels of IgG, IgA, IgM and lymphopenia with absent memory B cells, a diagnosis of common variable immunodeficiency was made. She started intravenous immunoglobulin replacement and prophylactic antibiotics. At age 20, small warts in hands that progressed to forearms, knees, abdomen and face were recorded. CXCR4 gene sequencing was done detecting a heterozygous p.Arg334STOP mutation, confirming WHIM syndrome. This disease is infrequent and difficult to diagnose.