Safety and Efficacy of Elosulfase Alfa in Australian Patients with Morquio a Syndrome: A Phase 3b Study

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.

Structured Dietary Management Dramatically Improves Marked Transaminitis, Metabolic and Clinical Profiles in Glycogen Storage Disease Type IXa

Abstract Glycogen storage disease type IXa (GSD IXa) presents in childhood with hepatomegaly, poor growth, and ketotic hypoglycemia. Clinical course is usually mild, often not requiring treatment with attenuation of symptoms with increasing age. The phenotypic spectrum has recently expanded to include more severe involvement with hepatic fibrosis or cirrhosis warranting dietary therapy. We report a 2-year-old boy with a severe phenotype of GSD IXa presenting with a massive hepatomegaly, significant transaminitis, recurrent ketotic hypoglycemia, and short stature. Aggressive dietary management with regular feeds, frequent uncooked cornstarch doses, and protein supplementation resulted in clinical improvements including enhanced growth velocity, energy levels, overall well-being, and reduction in hepatomegaly with restitutions in biochemical parameters. We concur with a recent report which proposed that GSD IXa is not always a mild condition but instead part of an expanding phenotypic spectrum warranting intensive dietary management to optimize metabolic control and quality of life.

Biochemical profiling in two siblings with mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency

We report the biochemical profiling in two siblings with mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency. Organic aciduria typical of this rare inborn error metabolism was found when the elder sibling presented with an episode of severe ketoacidosis at 20 months of age, which consisted of excessive excretion of ketones, tiglylglycine, 2-methyl-3-hydroxybutyrate, and 2-methylacetoacetate. Blood acylcarnitiness profile showed elevation of C5OH-carnitine, which represents 2-methyl-3-hydroxybutyrylcarnitine. A similar biochemical profile was identified in the younger sibling during screening although he had only mild clinical symptoms. Both patients reported a favourable outcome on follow-up.