Response of 33 UK patients with infantile-onset Pompe disease to enzyme replacement therapy.
BACKGROUND
Enzyme replacement therapy (ERT) for infantile-onset Pompe disease has been commercially available for almost 10 years. We report the experience of its use in a cohort treated at three specialist lysosomal treatment centres in the UK.


METHODS
A retrospective case-note review was performed, with additional data being gathered from two national audits on all such patients treated with ERT. The impact on the outcome of various characteristics, measured just prior to the initiation of ERT (baseline), was evaluated using logistic regression.


RESULTS
Thirty-three patients were identified; 13/29 (45%) were cross-reactive immunological material (CRIM) negative, and nine were immunomodulated. At baseline assessment, 79% were in heart failure, 66% had failure to thrive and 70% had radiological signs of focal pulmonary collapse. The overall survival rate was 60%, ventilation-free survival was 40% and 30% of patients were ambulatory. Median follow-up of survivors was 4 years, 1.5 months (range 6 months to 13.5 years). As with previous studies, the CRIM status impacted on all outcome measures. However, in this cohort, baseline failure to thrive was related to death and lack of ambulation, and left ventricular dilatation was a risk factor for non-ventilator-free survival.


CONCLUSIONS
The outcome of treated patients remains heterogeneous despite attempts at immunomodulation. Failure to thrive at baseline and left ventricular dilation appear to be associated with poorer outcomes.
Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospital Foundation Trust, Oxford Road, Manchester, UK. alexander.broomfield@cmft.nhs.uk.
A
A
Broomfield
Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospital Foundation Trust, Oxford Road, Manchester, UK.
J
J
Fletcher
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
J
J
Davison
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
N
N
Finnegan
Cardiology Department, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
M
M
Fenton
Department of Paediatric Cardiology, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK.
A
A
Chikermane
Regional Genetics Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
C
C
Beesley
Enzyme Unit, Chemical Pathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
K
K
Harvey
Enzyme Unit, Chemical Pathology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
E
E
Cullen
Department of Inherited Metabolic Disorders, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK.
C
C
Stewart
Department of Inherited Metabolic Disorders, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK.
S
S
Santra
Department of Inherited Metabolic Disorders, Birmingham Children's Hospital, Steelhouse Lane, Birmingham, UK.
S
S
Vijay
Department of Inherited Metabolic Disease, Guy's and St Thomas' NHS Foundation Trusts, Evelina London Children's Hospital, Westminster Bridge Road, London, UK.
M
M
Champion
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
L
L
Abulhoul
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
S
S
Grunewald
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
A
A
Chakrapani
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
M A
MA
Cleary
Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospital Foundation Trust, Oxford Road, Manchester, UK.
S A
SA
Jones
Metabolic Medicine Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
A
A
Vellodi
D009202:Cardiomyopathies / Q000378:metabolism / Q000401:mortality; D003429:Cross Reactions; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality*; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D012189:Retrospective Studies; D015996:Survival Rate; D006113:United Kingdom; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000401:mortality