SWORD: A simplified desensitization protocol for enzyme replacement therapy in adult Pompe disease.

Pompe disease is an inherited lysosomal disease in which there is a decrease or absence of acid alpha-glucosidase activity. This enzyme defect induces glycogen storage in different tissues, especially muscle and heart, resulting in muscle weakness, respiratory failure and heart disease. Substitutive enzyme replacement therapy (ERT) dispensed every two weeks is the only treatment that has shown benefits. However, this treatment induces hypersensitivity for half of the treated patients. Reactions range from mild to severe, sometimes requiring ERT suspension and anti-anaphylaxis drug administration. Understandably, high amount of acid alpha-glucosidase infusion seems to be identified by the immune system as a danger associated molecular pattern, and induce an immune reaction, involving sometimes, but not always, immunoglobulin E (IgE) production and activating mast and basophil polynuclear cells. Considering the lack of therapeutic alternatives and the proved benefit of ERT, desensitization finds its place here. We hereby report the case of a patient for whom a simplified desensitization protocol ("SWORD": Start With One Regular Drop) was successfully achieved, allowing ERT to be pursued, resulting eventually in clinical improvement.

Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years.

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.

Glucoamylase: another fungal enzyme associated with baker's asthma.

BACKGROUND: Aspergillus-derived enzymes are widely used as dough additives in the baking industry. These enzymes may give rise to immunoglobulin (Ig)E-mediated sensitization and occupational asthma. Glucoamylase (or amyloglucosidase) is an important industrial enzyme obtained from Aspergillus niger and used to provide fermentable sugars for yeast to improve loaf volume and texture. OBJECTIVE: The aim of our study was to investigate the potential allergenic role of glucoamylase in baker's asthma. METHODS: We report four subjects with work-related allergic respiratory symptoms who were exposed to glucoamylase and other starch-cleaving enzymes used as baking additives. The causative role of glucoamylase in work-related asthma was investigated by immunologic tests and specific inhalation challenges (SIC). Glucoamylase allergenic components were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. RESULTS: Skin prick tests to glucoamylase (10 mg/mL) gave a positive response in all patients. Further, a positive skin prick test to alpha-amylase was obtained in the four patients and to hemicellulase in two of them. SIC to glucoamylase elicited isolated early asthmatic responses in the three patients tested, and SIC to alpha-amylase elicited early asthmatic responses in two patients and a dual asthmatic response in another patient. Immunoblotting with glucoamylase showed several IgE-binding bands with molecular masses between 33 and 96 kD. IgE-inhibition assays showed scarce to moderate allergenic cross-reactivity between glucoamylase and alpha-amylase. CONCLUSIONS: These bakers had developed IgE-mediated occupational asthma to glucoamylase and alpha-amylase. Fungal glucoamylase is widely used as a baking additive and this enzyme may give rise to allergic respiratory reactions among exposed workers.