Proton nuclear magnetic resonance spectroscopic detection of oligomannosidic n glycans in alpha-mannosidosis: a method of monitoring treatment

Abstract

In Alpha-mannosidosis (MIM 248500) the patients accumulate mainly unbranched oligosaccharide chains in the lysosomes in all body tissues, including the brain. With ensuing therapeutic modalities in man (BMT and ERT) non-invasive methods of monitoring the effect of treatment are needed. Paramount is the possible effect of the treatment on the brain, since this organ is regarded as difficult to reach because of the blood-brain barrier. We therefore performed proton nuclear magnetic resonance spectroscopy (MRS) of the brain in two untreated patients, and a 16-year-old patient treated with BMT at the age of 10 to assess whether this non-invasive method could be applied in the monitoring of the accumulation of abnormal chemicals in the brain of patients. We found an abnormal peak that was not present in the treated patient. A similar pattern was also found in MRS of urine from patients, reflecting the concentration of oligosaccharides in serum and tissues. We therefore conclude that MRS can be a useful method to monitor the effect of treatment for Alpha-Mannosidosis.

Fig. 1

Upper spectrum: short echo-time proton spectroscopy of a 20 year old untreated patient taken in the region of the basal ganglia, with a broad elevation around 3.7 ppm.(arrow). Middle spectrum: short echo-time proton spectroscopy of a BMT treated patient taken in the region of the basal ganglia , with a mild broad elevation around 3.7 ppm (arrow) and somewhat elevated second Creatine peak at 3.9 ppm. Lower spectrum: Short echo-time proton spectroscopy of a control subject showing a normal spectrum, with normal amount of signal where our patients showed increased signal (arrow)

Fig. 2

In vitro spectroscopy scan of urine samples from a BMT treated patient(upper spectrum) and from a untreated patient(bottom spectrum), showing additional peaks in the untreated patient from 3.57 to 3.79 ppm(arrow) representing the oligosaccharides