title: Interleukin 7 receptor alpha-chain-mutation severe combined immunodeficiency without lymphopenia: correction with haploidentical T-cell-depleted bone marrow transplantation.
abstract: BACKGROUND
  Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency characterized by abnormal lymphocyte development and lymphopenia. It often presents during the first year of life with recurrent, opportunistic infections, failure to thrive, and malabsorption.
  
  
  OBJECTIVE
  To advocate newborn screening for SCID.
  
  
  METHODS
  We reviewed the case histories of dizygotic twins with Pneumocystis carinii pneumonia (PCP) at the age of 6 months.
  
  
  RESULTS
  Full-term fraternal twin girls were born to nonconsanguineous parents. Twin A developed recurrent oral candidiasis at 2 months, followed by pneumococcal bacteremia and PCP. At 5 months she had failure to thrive, but her absolute lymphocyte count was normal (5,887 cells/mm3). Subsequently, twin B presented with acute respiratory distress and was also diagnosed as having PCP; her absolute lymphocyte count was 5,852 cells/mm3. Flow cytometric analysis of peripheral blood lymphocytes from both girls demonstrated a T-B+NK+ phenotype consistent with interleukin 7 receptor alpha-chain-mutation SCID. Both girls received a haploidentical T-cell-depleted bone marrow transplant from their mother. In the interim, a homozygous point mutation in the interleukin 7 receptor alpha-chain gene was identified in twin B. Both parents were found to be carriers. Twin A died of chronic lung disease 8 months after transplantation; twin B is currently thriving.
  
  
  CONCLUSIONS
  Early diagnosis and treatment of SCID are associated with an increased rate of survival and improved long-term outcome. Some patients with SCID can present without lymphopenia. Thus, we advocate that more sensitive screening tests be considered for inclusion in the newborn screening program currently used in most states.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Schneider Children's Hospital, North Shore Long Island Jewish Health System, Great Neck, New York 11021, USA. punitaponda@hotmail.com
authors.forename: Punita
authors.initials: P
authors.lastname: Ponda
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Schuval
authors.forename: Blanka
authors.initials: B
authors.lastname: Kaplan
authors.forename: Peter
authors.initials: P
authors.lastname: Logalbo
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Roberts
authors.forename: Vincent R
authors.initials: VR
authors.lastname: Bonagura
mesh_terms: D016026:Bone Marrow Transplantation; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008231:Lymphopenia; D008403:Mass Screening; D009154:Mutation; D011020:Pneumonia, Pneumocystis / Q000150:complications; D020395:Receptors, Interleukin-7 / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics / Q000601:surgery*; D013601:T-Lymphocytes
chemical_list: D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain