Preliminary clinical efficacy and safety of BMN 701, GILT-tagged recombinant human acid alpha glucosidase (rhGAA), in late-onset Pompe disease: results of an extension study

Abstract

Metachromatic leukodystrophy (MLD) is a lysosomal disorder that results from the deficiency of the lysosomal enzyme arylsulfatase A. It is characterized by motor and developmental regression, seizures, deafness, blindness, dementia and premature death. There are three types of onsets: late infantile, juvenile, and adult. We performed a retrospective chart review of 71 patients (47 infantile, 23 juvenile) evaluated at the Program for Study of Neurodevelopment in Rare Disorders (NDRD) between January 2000 and August 2013. The patients were evaluated prospectively using a standardized protocol. The purpose of the study is to describe the natural course of the disease. In 31 patients only a baseline evaluation was available because they went on to receive umbilical cord blood stem cell transplantation. The data collected was extracted from the NDRD evaluations as well as any outside medical records that provided relevant information regarding symptoms and symptom onset. The results indicate that the patients with the late infantile form show severe deterioration over a short period of 36 months. The first symptoms for the late-infantile onset were reported at amedian age of 16months and included delay inwalking and changes in muscle tone. The median age for the children with juvenile onset was 60 months. While the patients with juvenile onset showed changes in muscle tone, attention and behavior problems were more often cited as the first cause of concern. The median age of diagnosis was 27 and 78.5 months for late-infantile and juvenile onset, respectively. The median age of walking was delayed at a median of 14 months for both groups. First words were reported at a median of 10 months for lateinfantile onset and 12 months for juvenile onset. In conclusion patients with MLD deteriorate very rapidly after the onset of symptoms. Currently there is an unacceptable delay between the parents initial concerns of their child and diagnosis, leaving a very small window of opportunity to treat the patient. Newborn screening will provide the opportunity for early diagnosis but since age of onset could vary recognizing first signs will be extremely important when counseling families about future interventions.