What is DBA?

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

2. n = 75

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

6. Vlachos, 2012

7. Vlachos A et al. Blood 2012;119:3815-3819

9. 17 patients had severe hepatic iron load (LIC >10 mg/g DW, maximum 38.6 mg/g DW): • 4 before initiation of chelation treatment • 8 following chelation with desferrioxamine • 5 following deferasirox treatment • 7 of the patients had severe hepatic iron load (maximum 29.17 mg/g DW) despite of maintaining the ferritin <1500 g/L with adequate chelation treatment following guidelines for thalassaemia. • Severe hepatic iron load was seen as early as in the second year of life (2 years 6 months LIC 38.6 mg/g DW). • 3 patients had cardiac iron load (T2* <20 ms) in childhood, including 2 below the age of 6 years. • 7 patients required intensification of chelation with continuous intravenous desferrioxamine, which was successful in all but one despite of the use of 50 mg/kg/day.

10. n=37

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

14. Hepatitis B vaccine Transfusions minimum to 12 months • Investigate immune system: • lymphocyte subsets • immunoglobulins • Immunoglobulin subclasses • responses to antibodies MMR Chickenpox vaccine trial of prednisolone 2 mg/kg for four weeks

15. 2 mg/kg alternate days wean alternate day over 8 weeks Response to steroids typical 1 mg every 6 weeks slow reduction over >6 months FerriScan under sedation prednisolone ≤0.5 mg/kg alternate days 5 to 10 years of age: MRI T2* Every 5 years: DEXA scan

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

17. bone marrow biopsy if cytopenia monitor film vitamin D yearly endocrinology review from 10 years of age until end of pubertal development