Transcript 1 – Dr Josu De La Fuente – What is DBA?

What is DBA?
Josu de la Fuente
St Mary’s Hospital
Imperial College London
n = 75
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
Development
• Learning difficulties
• Behavioural difficulties
Ophthalmological
• Congenital glaucoma
• Strabismus
• Congenital cataract
Neck and spine
• Short neck
• Webbed neck
• Sprengel deformity
• Klippel-Feil deformity
• Scoliosis
Hearing abnormalities
• Congenital deafness
• Middle ear abnormalities
Hand thumb anomalies
• Hypoplastic thumbs
• Triphalyngeal
• Absent thumbs
• Thenar hypoplasia
Growth
• Growth retardation
• Osteoporosis
• Feeding abnormalities
Urogenital anomalies
• Absent kidney
• Horseshoe kidney
• Hypospadias
Vlachos, 2012
Vlachos A et al. Blood 2012;119:3815-3819
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).
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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.
n=37
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
anaemia and low retics
>100 nmol/mg Hb/h
>1% or adjusted for age
negative
absence or reduction beyond proerythroblasts
negative
negative
• Mutation analysis
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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
MMR
Chickenpox vaccine
trial of prednisolone 2 mg/kg for four weeks
Response to steroids
wean alternate
day over 8 weeks
typical 1 mg every 6 weeks
prednisolone ≤0.5 mg/kg alternate days
2 mg/kg
alternate days
slow reduction over >6 months
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
bone marrow biopsy if cytopenia
monitor film
vitamin D
yearly endocrinology review from 10 years of age
until end of pubertal development