Effects of family history and consanguinity in primary immunodeficiency diseases in children in Qatar

Background: The high consanguinity in Middle East increases the risk of genetic diseases, including primary immunodeficiency diseases (PID). Objectives: This study was aimed at determining the rate of positive family history of PID, the overall rate and type of consanguinity, and their effects on delay age during diagnosis of PID. Materials and methods: A retrospective analysis was conducted on 131 children with PID (aged 0 - 14 years) managed at Hamad General Hospital during 1998-2012. Results: Data on 131 patients (75 males & 56 females) of 82 families was analyzed. The most common phenotype of PID was predominantly antibody deficiency (23.7%). The onset age was 24.01 months and delay age 18.7 months. Family history of PID was 66.4% (38.7% in predominantly antibody deficiency and 100% in diseases of immune dysregulation). Positive family history significantly (p = 0.004) reduced the delay age of PID diagnosis by 52.9%. The consanguinity rate was 61.1% (32.3% in the predominantly antibody ID to 96% in the phagocyte defects group), where paternal cousin ranked the highest type (57.5%). Conclusions: This study indicates that family history is common in children with PID and helpful in reducing the delay age. Consanguinity among families of affected children is also high (higher than healthy population). Paternal parallel cousin marriages are the most common type of consanguinity. For a practicing physician, family history is a simple and useful tool when suspecting PID in children. Primary prevention of PID in Middle East communities should consider consanguinity reduction through public awareness and education and premarital counseling programs.

Clinico-Radiological Correlation in Children with Ataxia Telangiectasia in Qatar

Introduction: Ataxia telangiectasia (AT) is a rare disease characterized by immunodeficiency and neurological manifestations. Ataxia, resulting from cerebella atrophy, runs a progressive incapacitating course. Clinical monitoring of the disease course is mandatory for early treatment. Aim: To study clinical severity of AT and correlate it with the degree of cerebellar atrophy. Patients and Methods: We retrospectively studied all children (less than 14 years) with AT seen at Hamad General Hospital Clinics between 1998-2013. We collected basic demographic data, parental consan-guinity, family history, AT clinical severity scores, and reviewed CBC with differential counts;alpha-fetoprotein, serum immunoglobulins and lymphocyte subsets. Cranial MRI scans of each subject were reviewed by a neuroradiologist. Cerebellar atrophy was visually and semi-quantitatively scored. Results: We analyzed data on 18 AT children (10 males and 8 females), mean age of 76.9 months. 77.8% had a positive family history of AT and 41.7% parental consanguinity. Lymphopenia was observed in 77.8% and high serum alpha-fetoprotein in 87.5% of children. Clinical severity of ataxia was 17.1 ± 8.4 (mean ± SD);86.7% of patients were moderate-severe. MRI cerebellar atrophy score was 1.9 ± 1.3 (mean ± SD), and moderate in 51% of patients. AT clinical severity score correlated (coefficient r = 0.566) but not statistically significant p = 0.088) with MRI cerebellar atrophy scores. Conclusions: Moderate to severe ataxia and marked cerebellar atrophy are quite common in AT children. There is a correlation between AT clinical severity and cerebellar atrophy. Larger prospective studies might further determine the significance of our observations and help practicing practitioners monitor the progression of the disease.