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