Disorder
Neutropenic immunodeficiency, plus

Clinical Characteristics

General description (for patients):

This disease leads to decreased numbers and efficiency of certain white blood cells important to fighting infections.  Affected individuals suffer from lung and respiratory infections and growth retardation.  They are also short in stature, have a coarse facies, and a light complexion with white hair.

Medical description (for healthcare providers):

This is a primary immunodeficiency disorder found in a single Mennonite family (4 of 15 offspring).  The phenotype consists of short stature, hypopigmented skin with white hair, recurrent bronchopulmonary infections, especially those due to S. pneumoniae, coarse facies, and congenital neutropenia.  The short stature distinguishes it from other hypopigmentary disorders with defects in lysosomal secretion such as Chediak-Higahi and Hermansky-Pudlack syndromes.  The neutropenia in this immunodeficiency disorder responds to granulocyte-colony stimulating factor (G-GSF).  Serum IgM levels are low and adolescent individuals may have low IgG levels as well. Melanosome maturation is defective in basal keratinocytes accounting for the hypopigmentation.

Genetics:

Parental consanguinity is unknown in this Mennonite family but affected individuals of both sexes were homozygous for a 23A>C mutation in p14 (MAPBPIP) on chromosome 1 (1q21).  This defect results in decreased p14 activity causing RNA instability and aberrant lysosomal function.

Management:

Administration of low levels of G-GSF corrects the neutropenia but its impact on other phenotypic features are unknown.

Prompt and vigorous treatment of bronchopulmonary infections.

Prognosis:

Unknown.  Several patients have lived at least to adolescence.

Specialists and specialty centers:

Immunologist, Pulmonologists, Infectious Disease Specialist.

References:

Bohn, H., Allroth, A., Brandes, G., Thiel, J., Glocker, E., Schaffer, A.A., Rathinam, C., Taub, N., Teis, D., Zeidler, C., Dewey, R.A., Geffers, R., Buer, J., Huber, L.A., Welte, K., Grimbacher, B., and Klein, C.:   A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14.  Nat. Med. 13: 38-45, 2007.  PubMed ID: 17195838

Resources:

Immune Deficiency Foundation