title: Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years.
abstract: Pompe disease is an autosomal recessive disease resulting from deficiency of the acid alpha-glucosidase (GAA). The late-onset Pompe Disease (LOPD) patients develop muscular and respiratory complications later in life. We describe a retrospective observational cohort study including 22 patients with LOPD. The cohort was assessed at baseline before Enzyme Replacement Therapy (ERT) with alglucosidase alpha (20mg/kg biweekly) was commenced and subsequently relevant information was collected at 2, 4 and 5years later. The median age of the patients at study entry was 44years (16-64years), with median disease duration of 11.5years (4-31years). At baseline, 10 patients (45%) could walk without support, 12 (55%) could walk with unilateral or bilateral support including 3/12 were wheelchair bound. Mean predicted FVC % was 55.7 (95% CI 45-66) of predicted normal at baseline and showed no significant change after 5years (54.6 (95% CI 43-66)), (all p=0.9815). Mean FVC % supine was 41.8 (95% CI 33.8-49) of predicted normal at baseline and remained significantly unchanged at 5years (48.4 (95% CI 37-59.6)), (all p=0.8680). The overnight non-invasive ventilator dependence increased by 18.2% as compared with baseline and requirement of mobility aids increased during this period by 5.2% as compared with the baseline. Mean walking distance at 6min walk test was 411.5 (95% CI 338-485) at baseline, 266.5 (95% CI 187-346) m at 2years, 238.6 (95% CI 162-315) m at 4years and 286.8 (95% CI 203-370) m at 5years (p=0.1981; ANOVA was completed only for 14 patients). A gradual decline in FVC% predicted was noted only in four cases and a decline in FVC% supine in two other. Only one patient showed a decline in both pulmonary function tests. In all remaining cases (17/22) respiratory function remains stable. In conclusion overall pulmonary function tests and mobility remained stable for 5years in majority of patients on ERT. However, in some patients they continued to decline in spite of ERT resulting in increased number of patients requiring ventilation and increase wheel chair dependence at the end of 5years.
authors.affiliation: Adult Inherited Metabolic Disorders, The Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Stott Line, M6 8HD, Salford, UK. Electronic address: kstepien@doctors.org.uk.
authors.forename: Karolina M
authors.initials: KM
authors.lastname: Stepien
authors.affiliation: Adult Inherited Metabolic Disorders, The Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Stott Line, M6 8HD, Salford, UK; University of Pretoria, Department of Pediatrics and Child Health, Steve Biko Academic Hospital, South Africa.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hendriksz
authors.affiliation: Neurology Department, Salford Royal Foundation NHS Trust, Stott Lane, Salford, M6, 8HD.
authors.forename: Mark
authors.initials: M
authors.lastname: Roberts
authors.affiliation: Adult Inherited Metabolic Disorders, The Mark Holland Metabolic Unit, Salford Royal NHS Foundation Trust, Stott Line, M6 8HD, Salford, UK.
authors.forename: Reena
authors.initials: R
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D056947:Enzyme Replacement Therapy; D005260:Female; D005087:Glucan 1,4-alpha-Glucosidase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005087:Glucan 1,4-alpha-Glucosidase
keywords: Alpha glucosidase deficiency; Enzyme replacement therapy; LOPD; Late-onset Pompe disease; Myozyme