Ataxia Telangiectasia

Transcription

1 Ataxia Telangiectasia Dr. Ifat Sarouk Pediatric Pulmonology Unit The National AT Center The Edmond and Lili Safra Children s Hospital Sheba Medical Center, Tel Hashomer

2 What is AT? Autosomal recessive disorder Mutations in the ATM (AT mutated) gene Chromosome 11q.26 Protein kinase Critical role in cellular responses- particularly DNA breaks

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4 Incidence Approximately 1/300,000 births

5 Clinical Features Neurology: Progressive manifestation Tremor,Chorea Dystonia, Ataxia Oculomotor apraxia Dysphagia

6 Clinical Features Immunological abnormalities Immunoglobulin deficiency Poor responsiveness to pneumococcal vaccine Reduced lymphocyte numbers Thymic hypoplasia

7 Clinical Features Recurrent infection Lungs Ears Sinuses

8 Clinical Features Malignancies: Increased risk (22%) Particularly T, B leukemias Endocrine malignancy Breast cancer Increased radio-sensitivity to ionizing radiation

9 Clinical Features Oculomotor telangiectasia Slow grow Delayed puberty Diabetes mellitus- 25%

10 Diagnosis Clinical suspicion Genetic confirmation Chromosomal radio-sensitivity analysis ATM protein Alpha fetoprotein ATM gene sequencing

11 Patient Distribution Across Israel Center 9 North - 12 patients Netivot 3 Jerusalem- 3 Qseifeh - 9

12 Israeli Patient Data 34 patients 3 p suspected AT 8 p malignancy (23%) 19 p- IVIG (55%) 4 p PEG (11%)

13 Israeli Patient Data Malignancy Last 5 Years Other, 2 Hodgkins Lymphoma, 1 Carcinoma, 1 B cell Lymphoma, 7 Burkitts ly, 3 ALL, 8

14 Lung disease kills more AT patients then any cancer

15 Lung Disease Respiratory infection- acute and chronic Aspiration syndrome Scoliosis Respiratory muscle weakness Post chemotherapy Interstitial lung disease

16 The Effect of Vital Capacity Declining to Tidal Volume Range on Mid-Forced Expiratory Flows and Life Span in Ataxia Telangiectasia Vilozni D, Sarouk I, Lavie M, Bar B, Dagan A, Levi Y, Askenazi M, Ofek M, Efrati O

17 The Effect of Vital Capacity Declining To Tidal Volume Range Vital Capacity values decline with progress of disease. Deterioration in VC may be a major prognostic factor

18 The Effect of Vital Capacity Declining To Tidal Volume Range Yearly best spirometry data was collected over 5-7 Y The collected data included: Anthropometric and best yearly spirometry data initial age and duration of wheelchair confinement

19 Results FVC decrease with progress of disease FEF25-75 declines from % predicted as lung disease progresses

20 An abrupt elevation in the ratios below 2 years prior to end stage lung disease

21 Effectiveness of Cough Assist in Improvement of Lung Volume in Ataxia Telangiectasia (A-T) Ifat Saruk MD,Gil Sokol BPT, Ran Hakimi BPT, Nir Helper BP Daphna Vilozni PhD,Moran lavie MD, Ori Efrati MD

22 Effectiveness of Cough Assist in Improvement of Lung Volume in Ataxia Telangiectasia Objective: Evaluate the effect of C-A on lung function in patients with A-T 5 A-T patients, mean age 11 y pulmonary function test (PFT) before and after coughing with the assistance of the C-A

23 Effectiveness of Cough Assist

24 Effectiveness of Cough Assist- Results 3 patients (60%) improved FVC more than 10% above baseline values. 4 patients (80%) improved PEF more than 10% above baseline values. 3 patients (60%) improved MEF25-75 more than 20% above baseline values.

25 Summary AT is an extremely rare disease Israel is a small country Lung disease is a leading cause of death We need to know how to treat AT patients when we meet them