Brain MRI findings in aspartylglucosaminuria.

BACKGROUND AND PURPOSE: The aim of this study was to identify characteristic 3.0 T brain MRI findings in patients with aspartylglucosaminuria (AGU), a rare lysosomal storage disorder. Previous AGU patient material imaged at 1.0 and 1.5 T was also re-evaluated. MATERIALS AND METHODS: Twenty-five brain MRI examinations from 20 AGU patients were included in the study. Thirteen patients underwent a prospective 3.0 T MRI (5 male, 8 female, aged 9-45 years). Twelve examinations from nine patients (4 male, 5 female, aged 8-33 years) previously imaged at 1.0 or 1.5 T were re-evaluated. Two patients were included in both the prospective and the retrospective groups. Visual analysis of the T1- and T2-weighted images was performed by two radiologists. RESULTS: The previously reported signal intensity changes in T2-weighted images were visible at all field strengths, but they were more distinct at 3.0 T than at 1.0 or 1.5 T. These included signal intensity decrease in the thalami and especially in the pulvinar nuclei, periventricular signal intensity increase and juxtacortical high signal foci. Poor differentiation between gray and white matter was found in all patients. Some degree of cerebral and/or cerebellar atrophy and mild ventricular dilatation were found in nearly all patients. This study also disclosed various unspecific findings, including a higher than normal incidence of dilated perivascular spaces, arachnoid cysts, pineal cysts and mildly dilated cavum veli interpositi. CONCLUSION: This study revealed particular brain MRI findings in AGU, which can raise the suspicion of this rare disease in clinical practice.

Susceptibility-Weighted Imaging Findings in Aspartylglucosaminuria.

BACKGROUND AND PURPOSE: Aspartylglucosaminuria is a rare lysosomal storage disorder that causes slowly progressive, childhood-onset intellectual disability and motor deterioration. Previous studies have shown, for example, hypointensity in the thalami in patients with aspartylglucosaminuria on T2WI, especially in the pulvinar nuclei. Susceptibility-weighted imaging is a neuroimaging technique that uses tissue magnetic susceptibility to generate contrast and is able to visualize iron and other mineral deposits in the brain. SWI findings in aspartylglucosaminuria have not been reported previously. MATERIALS AND METHODS: Twenty-one patients with aspartylglucosaminuria (10 girls; 7.4-15.0 years of age) underwent 3T MR imaging. The protocol included an SWI sequence, and the images were visually evaluated. Thirteen patients (6 girls, 7.4-15.0 years of age) had good-quality SWI. Eight patients had motion artifacts and were excluded from the visual analysis. Thirteen healthy children (8 girls, 7.3-14.1 years of age) were imaged as controls. RESULTS: We found a considerably uniform distribution of decreased signal intensity in SWI in the thalamic nuclei in 13 patients with aspartylglucosaminuria. The most evident hypointensity was found in the pulvinar nuclei. Patchy hypointensities were also found especially in the medial and anterior thalamic nuclei. Moreover, some hypointensity was noted in globi pallidi and substantia nigra in older patients. The filtered-phase images indicated accumulation of paramagnetic compounds in these areas. No abnormal findings were seen in the SWI of the healthy controls. CONCLUSIONS: SWI indicates accumulation of paramagnetic compounds in the thalamic nuclei in patients with aspartylglucosaminuria. The finding may raise the suspicion of this rare disease in clinical practice.

Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan.

BACKGROUND: Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging. CASE REPORT: We encountered a 16-year-old boy who began to show difficulties in his speech at the age of 6years. Due to a mild regression in his development, he gradually lost common daily abilities. His diagnosis was first obtained through exome sequencing that identified a novel homozygous mutation in the AGA gene. This result was reasonable because of parental consanguinity. Reduced enzymatic activity of AGA was then confirmed. His urine was retrospectively screened by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and a specific pattern of abnormal metabolites was identified. CONCLUSIONS: Because both exome sequencing and MALDI-TOF-MS screening are adaptable and comprehensive, future combinatory use of these methods would be useful for diagnosis of rare inborn errors of metabolism such as AGU.

Brain MRI findings in two Turkish pediatric patients with aspartylglucosaminuria.

Aspartylglucosaminuria is a rare lysosomal storage disorder that occurs as a result of a deficiency of the aspartylglucosaminidase enzyme. Because the disease is commonly referred to as the Finnish disease heritage, it is underdiagnosed outside of Finland. To date, only three Turkish patients are described in the literature. Here we describe the clinical and brain magnetic resonance imaging findings in two Turkish cousins with aspartylglucosaminuria, which can raise the suspicion of this rare disease in clinical practice.