1. What is DBA? Josu de la Fuente St Mary’s Hospital Imperial College London

2. born at term following normal pregnancy low birth weight progressive feeding problems and pale Hb 26 g/dL born at term following normal pregnancy abnormalities thumbs of both hands extra digit left hand ASD deafness left ear frequent infections anaemia with pregnancy premature birth cleft palate anaemia discovered when cleft palate operation at 15 months very poor growth in antenatal scans excess of water (polyhydramnios) reflux VSD grommets frequent tonsillitis and ear infections behavioural and learning defficulties anaemia at 5 years premature birth ASD short stature osteoporosis and scoliosis anaemia at 23 years of age ?

5. Physical features Craniofacial features Cathie face High arched palate Cleft palate and lip Microcephaly Cardiac anomalies Ventricular septal defect Atrial septal defect Coarctation of the aorta Complex anomalies Urogenital anomalies Absent kidney Horseshoe kidney Hypospadias Growth Growth retardation Osteoporosis Feeding abnormalities Ophthalmological Congenital glaucoma Strabismus Congenital cataract Neck and spine Short neck Webbed neck Sprengel deformity Klippel-Feil deformity Scoliosis Hand thumb anomalies Hypoplastic thumbs Triphalyngeal Absent thumbs Thenar hypoplasia Development Learning difficulties Behavioural difficulties Hearing abnormalities Congenital deafness Middle ear abnormalities

8. Vlachos, 2012

9. Strategy Iron Infections BM reserve Disability

10. 1 pack of red cells = min 200 mg

11. Cohen, A. R. et al. Hematology 2004;2004:14-34 Relation of Myocardial T2* and Liver Iron Cohen, A. R. et al. Hematology 2004;2004:14-34 Discordance of Liver and Myocardial Iron Cohen, A. R. et al. Hematology 2004;2004:14-34 Relation of Myocardial T2* to Left Ventricular Size and Function Iron Load

13. Number of patients examined 60 Males33 Females27 Number of patients with dental caries13 Number of patients with enamel defects28 Number of patients with previous dental extractions4 Dental Problems

14. anaemia and low retics >100 nmol/mg Hb/h >1% or adjusted for age negative absence or reduction beyond proerythroblasts negative Presentation Before first transfusion: FBC and reticulocytes eADA HPLC serology for parvovirus, hepatitis B, hepatitis C and HIV Diagnosis: Bone marrow biopsy: aspirate and trephine cytogenetic analysis and FISH parvovirus PCR Mutation analysis examine for skeletal abnormalities: palate, limbs, spine and scapula testicles USS abdomen echocardiogram hearing test ophthalmology review

15. hepatitis B vaccine transfusions minimum to 12 months Investigate immune system: lymphocyte subsets immunoglobulins immunoglobulin subclasses responses to antibodies trial of prednisolone 2 mg/kg for four weeks MMR Chickenpox vaccine BM biopsy cellularity

16. Response to steroids wean alternate day over 8 weeks 2 mg/kg alternate days slow reduction over >6 months typical 1 mg every 6 weeks prednisolone ≤0.5 mg/kg alternate days FerriScan under sedation 5 to 10 years of age: MRI T2* Every 5 years: DEXA scan

17. Unresponsive to steroids wean over two weeks 1.Transfusions: according to exercise tolerance and growth Blood usage <250 mL/kg/year 2.Chelation treatment 2 years of age: FerriScan under sedation liver biopsy bone marrow biopsy Every five years: DEXA scan MRI T2* Sibling BMT

18. Monitor blood film vitamin D bone marrow biopsy yearly endocrinology review from 10 years of age until end of pubertal development dental review