what is dba? josu de la fuente st mary’s hospital imperial college london
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What is DBA?
Josu de la FuenteSt Mary’s Hospital
Imperial College London
n = 75
Physical featuresCraniofacial 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
Vlachos, 2012
Vlachos A et al. Blood 2012;119:3815-3819
• 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.
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).
n=37
anaemia and low retics>100 nmol/mg Hb/h>1% or adjusted for agenegative
absence or reduction beyond proerythroblastsnegativenegative
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• echocardiogramme• hearing test• ophthalmology review
Hepatitis B vaccine
Transfusions minimum to 12 months
Investigate immune system:•lymphocyte subsets•immunoglobulins•Immunoglobulin subclasses•responses to antibodies
MMRChickenpox vaccine
trial of prednisolone 2 mg/kg for four weeks
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
Unresponsive to steroids
wean over two weeks
Transfusions:•according to exercise tolerance and growth•<250 mL/kg/year
2 years of age:•FerriScan under sedation•liver biopsy•bone marrow biopsy
Every five years:•DEXA scan•MRI T2*
Sibling BMT
monitor filmvitamin D
bone marrow biopsy if cytopenia
yearly endocrinology review from 10 years of age until end of pubertal development