Comprehensive genetic testing for primary immunodeficiency disorders in a tertiary hospital: 10-year experience in Auckland, New Zealand.

See-Tarn Woon,Rohan Ameratunga

doi:10.1186/s13223-016-0169-2

Abstract

Background and purposeNew Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs).MethodsSince 2005, we have offered a comprehensive genetic testing service for PIDs and other immune-related disorders with a published sequence. Here we present results for this program, over the first decade, between 2005 and 2014.ResultsWe undertook testing in 228 index cases and 32 carriers during this time. The three most common test requests were for X-linked lymphoproliferative (XLP), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and haemophagocytic lymphohistiocytosis (HLH). Of the 32 suspected XLP cases, positive diagnoses were established in only 2 patients. In contrast, genetic defects in 8 of 11 patients with suspected X-linked agammaglobulinemia (XLA) were confirmed. Most XLA patients were initially identified from absence of B cells. Overall, positive diagnoses were made in about 23% of all tests requested. The diagnostic rate was lowest for several conditions with locus heterogeneity.ConclusionsThorough clinical characterisation of patients can assist in prioritising which genes should be tested. The clinician-driven customised comprehensive genetic service has worked effectively for New Zealand. Next generation sequencing will play an increasing role in disorders with locus heterogeneity.

Highlights

IntroductionNew Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million
Background and purposeNew Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million
Thorough clinical characterisation of patients can assist in prioritising which genes should be tested

Summary

Introduction

New Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs). Failure to effectively combat infections is a hallmark of immunodeficiencies (IDs) such as primary immunodeficiency disorders (PIDs) where rare genetic defects lead to compromised host defences. Some patients develop autoimmunity and malignancy because of immune dysregulation [2, 3]. The severity of these disorders ranges from asymptomatic IgA deficiency to life. Grafton, Auckland 1148, New Zealand threatening conditions such as severe combined immunodeficiency (SCID). A delayed diagnosis can impact on prognosis if a patient has a life threatening disorder, such as presymptomatic males with X-linked lymphoproliferative syndrome (XLP) from SH2D1A or BIRC4 mutations [5]

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Conclusion