J ALLERGY CLIN IMMUNOL

VOLUME 125, NUMBER 2

Abstracts AB75

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294 Microarray Analysis of Candidate Genes in MultipleIntestinal Atresia with Immunodeficiency

K. Chen, S. A. McGhee, E. R. B. McCabe; UCLA, Los Angeles, CA.

RATIONALE: Multiple intestinal atresia with immunodeficiency (MIA-

I) is a rare disorder characterized by multiple atretic regions throughout

the gut in addition to varying forms of combined immunodeficiency. The

affected bowel demonstrates a histological sieve-like appearance, and sur-

vival is extremely poor. The pathogenesis remains unknown, but familial

case reports suggest an autosomal recessive pattern of inheritance. DNA

microarray analysis was performed in a cohort with MIA-I to identify can-

didate genes.

METHODS: Clinical history was obtained from medical records. DNA

was isolated from whole blood and/or saliva of living individuals with

MIA-I and their families. For deceased individuals with MIA-I, DNA

was isolated from paraffin-embedded tissues. Genotyping and copy num-

ber variation analysis was completed using a genome-wide SNP microar-

ray platform. Transmission/disequilibrium test analysis was performed to

identify associations with the MIA-I phenotype.

RESULTS: SNP genotyping and genetic analysis of three families with

MIA-I identified potential gene candidates. Initial homozygosity mapping

of microarray data from one family did not identify SNP associations.

Copy number variation analysis of an early candidate gene, CASR, did

not identify significant differences.

CONCLUSIONS: Multiple intestinal atresia with immunodeficiency re-

sults in total loss of gut function and has an extremely poor prognosis.

SNP microarray analysis can be used to identify gene candidates in this

rare disorder. However, collaboration with other major referral centers

will be extremely important in studying additional patients to delineate

the pathogenesis of MIA-I.

295 Combined Immunodeficiencies: Clinical, ImmunologicalFeatures And Outcome Of 56 Cases From A Single Institution

A. _Ikinciogulları1, F. Dogu1, C. Aytekin2, F. E. Cxipe1, M. Y€uksek3,

G. Bozdogan4, A. Yıldıran5, D. G€uloglu1, E. Babacan1; 1Ankara University,

School of Medicine, Department of Pediatric Immunology-Allergy, Ankara,

TURKEY, 2Dr. Sami Ulus Training and Research Children’s Hospital,

Department of Pediatric Immunology, Ankara, TURKEY, 3Zeynep Kamil

Training and Research Hospital, Department of Pediatric Immuno-

logy, _Istanbul, TURKEY, 4Acıbadem Hospital, Department of Pediatric

Immunology-Allergy, _Istanbul, TURKEY, 5Ondokuz Mayıs University,

School of Medicine, Department of Pediatric Immunology, Samsun,

TURKEY.

RATIONALE: Combined T and B cell Immunodeficiencies (CID) com-

prise a collection of genetic defects that involve both cellular and humoral

immunity.

METHODS: In this retrospective study, an analyze regarding to clinical,

immunological features and outcome of CID patients followed up between

1999-2009 at the Department of Pediatric Immunology and Allergy of

Ankara University are given.

RESULTS: Patient’s diagnosis are as follows: Severe combined immuno-

deficiency (SCID) (n531), Omenn’s Syndrome (n56), PNP Deficiency

(n52), MHC Class I Deficiency (n54), MHC Class II Deficiency (n59),

CD40 Ligand Deficiency (n52), DNA Ligase 4 Deficiency (n51) and

Stat5b Deficiency (n51). Twenty-one out of 56 cases (37.5%) are girls

and the rest are boys. Parental consanguinity varies beetween 57-100%

in different subgroups. Median age at diagnosis is 5.5, 4.2, 32, 16, 6,

11.5 months in SCID, Omenn’s Syndrome, PNP Deficiency, MHC Class

I Deficiency, MHC Class II Deficiency, CD40 Ligand Deficiency respec-

tively. Among SCID cases, T-B-NK+ (55%) is found to be the most com-

mon immunophenotype. 27 patients among 56 (19 SCID, 2 Omenn’s

Syndrome, 3 MHC Class II Deficiency, 1 CD40L deficiency, 1 DNA

Ligase 4 Deficiency, 1 PNP Deficiency) treated with hematopoietic stem

cell transplantation (HSCT). Donor origin was matched related family

members in 14 patients and haploidentical parents in 13. The overall sur-

vival is 63% following HSCT.

CONCLUSIONS: T-B- SCID subtype seems to be the most prominent

group among combined immunodeficiencies due mainly to high parental

consanguinity rate in Turkey. Life expectancy other than HSCT is very

short and unfavourable in severe clinical forms of CID.

296 "Diverse Clinical and Immunologic Phenotypes in Patientswith Autosomal Recessive Hyper-IgM Syndrome Caused byMutations in the AICDA Gene"

T. Harvey, K. Paris; LSU Health Sciences Center, New Orleans, LA.

RATIONALE: Patients with Hyper-IgM syndrome (HIGM) caused by

mutations in activation-induced cytidine deaminase (AICDA) are rare,

and novel mutations may have unique clinical presentations and outcomes

that differ from other forms of HIGM.

METHODS: Using chart review, three patients with HIGM due to AICDA

mutations were identified at our regional referral center and their clinical

and immunologic phenotypes and genotype were compared.

RESULTS: Three male patients were found to have AR HIGM. Clinical

presentation varied from 1 to 5 years of age. Patient 1 presented at age 5

years with a complex history of knee and joint pain since age 2 years.

He had no history of recurrent sinopulmonary infections. Patient 2 pre-

sented at age 17 months with recurrent sinopulmonary infections since

age 1 month. Patient 3 (sibling of patient 2) presented at age 1 year with

infections since age 1 month. Despite his known family history, he had

not been evaluated earlier. At diagnosis, all patients had hypogammaglob-

ulinemia with elevated IgM concentrations ranging from 197 mg/dl to

1920mg/dl. Sequencing analysis of the AICDA gene showed a missense

mutation (p.Ala111Glu) in patient one and 2 missense mutations

(p.Phe11Ile and p.Gly100Ala) in the second and third patients. All three

patients improved clinically on IgG replacement therapy.

CONCLUSIONS: HIGM caused by AICDA mutations causes defective

immunoglobulin diversification with varying clinical manifestations but

not all patients present with recurrent infections. Recognition of the nonin-

fectious complications associated with these genetic defects is essential for

proper diagnosis and treatment, which improve quality of life and may be

lifesaving.

297 Mortality Among Primary Immunodeficient Patients in KuwaitW. Al-Herz; Al-Sabah Hospital, Kuwait, KUWAIT.

RATIONALE: The aim of this project is to report mortality among pri-

mary immunodeficient patients in Kuwait.

METHODS: Data were obtained from Kuwait National Primary

Immunodeficiency Disorders Registry which was established in 2004.

RESULTS: A total of 114 patients were registered (male: female ratio

51.3), with a follow-up of 65.23 months. The distribution of these patients

according to each primary immunodeficiency category was: combined T-

and B- cell immunodeficiencies (24%), predominantly antibody immuno-

deficiency (27%), other well defined immunodeficiencies (27%), diseases

of immune dysregulation (13%), congenital defects of phagocyte number,

function or both (6%) and complement deficiencies (3%). There were 26

deaths (23%) with male: female ratio of 0.85. The deaths were between

0.2 and 61.33 months after diagnosis. The age of death ranged between

2 to 156 months, with a mean of 23.04+33.32 months. Sixteen deaths

(62%) were in the combined T-and B- cell immunodeficiencies group

with a mean age of death in this group of 10.06+7.46 months. The overall

post-diagnosis survival rate was 77.2% during the whole follow-up period.

The patients’ survival was influenced by gender, primary immunodefi-

ciency category, consanguineous marriages in the patients’ families, fam-

ily history of primary immunodeficiency, use of IVIG and antimicrobials

prophylaxis, and younger age at presentation. The causes of death in the

reported patients were respiratory failure with ARDS secondary to pneu-

monia, sepsis, liver, renal and multiorgan failure.

CONCLUSIONS: Our data show a high mortality rate among the

registered patients probably related to the high number of patients with

combined T- and B- cell immunodeficiencies.