PMC6148323_01
Pedigrees of the 2 Families and Gene Mutations. Pedigrees of patient 1 (A) and patient 2 (B) and electropherograms showing the DNA sequences of GBE1 exon 12 in both patients and exon 15 in patient 2 (C). The nucleotide change causing the arginine to histidine substitution is indicated by an asterisk. The CA dinucleotide deletion leading to a premature stop codon is shown by the arrow. Square represents a male individual; circle, a female individual; shading, an affected individual; slash mark, a deceased individual; and central dot, a carrier. d. 3 y Indicates died at age 3 years.
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F1
Patient 2 (Figure 1B), a 43-year-old man of Italian origin, was referred because of recurrent neurological problems. Sequencing of the GBE1 gene in patient 1 disclosed a previously described homozygous c.1544G>A (p.R515H) mutation in exon 12 (Figure 1C).
PMC6148323_02
Pedigrees of the 2 Families and Gene Mutations. Pedigrees of patient 1 (A) and patient 2 (B) and electropherograms showing the DNA sequences of GBE1 exon 12 in both patients and exon 15 in patient 2 (C). The nucleotide change causing the arginine to histidine substitution is indicated by an asterisk. The CA dinucleotide deletion leading to a premature stop codon is shown by the arrow. Square represents a male individual; circle, a female individual; shading, an affected individual; slash mark, a deceased individual; and central dot, a carrier. d. 3 y Indicates died at age 3 years.
nihms-984785-f0001.jpg
PMC6148323_02_nihms-984785-f0001.jpg
F1
Patient 2 (Figure 1B), a 43-year-old man of Italian origin, was referred because of recurrent neurological problems. Sequencing of the GBE1 gene in patient 1 disclosed a previously described homozygous c.1544G>A (p.R515H) mutation in exon 12 (Figure 1C).
Polyglucosan Bodies in Sural Nerve. A and B, Polyglucosan bodies appear faintly basophilic with hematoxylin-eosin stain (A) but show intensely positive reactions with periodic acid-Schiff stain (B). C, Polyglucosan bodies are surrounded by neural filament-positive material. D, Luxol fast blue staining for myelin also localizes polyglucosan bodies in neuronal axons (arrowhead). E and F, Electron micrographs show storage of thin filamentous material in the cytosol (E) and within a myelinated nerve fiber surrounded by several Schwann cell processes (F). Original magnification x40 (B and C), x60 (A and D), x4000 (F), and x6000 (E).
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F2
A sural nerve biopsy specimen from patient 1 revealed intracytoplasmic inclusions in neuronal axons (Figure 2). The arrow in Figure 2 points to a polyglucosan body surrounded by blue myelin stain.
Brain Magnetic Resonance Imaging in Patient 2. Brain magnetic resonance images of patient 2 showed the typical cerebral and spinal pattern described in patients with adult polyglucosan body disease. A-H, Fluid-attenuated inversion recovery sequences showed symmetric hyperintense white matter lesions in the pyramidal tracts of the medulla (A), pons (B), cerebellar peduncles (C), and periventricular regions (D-G), as well as (to a lesser degree) in the external capsule and the posterior limb of the internal capsule (D) and in subcortical areas (H). I, Axial T1-weighted sequences showed medullary, spinal, and vermian atrophy. J, The T2-weighted images showed a similar but less well-defined pattern. K and L, The abnormal white matter areas had normal signal on T1-weighted images and showed no enhancement after contrast administration.
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F3
Medullary, vermian, and spinal atrophy was also observed at cervical and dorsal levels (Figure 3 and eFigure in the Supplement).
Longitudinal Study of Brain Magnetic Resonance Imaging in Patient 2. Sequential brain magnetic resonance images of patient 2 in 2006 (A, D, G, and I), 2008 (B and E), and 2012 (C, F, H, and J) showed mild increases in the size of white matter lesions in the cerebellar peduncles (C and F). All other lesions were unchanged during the follow-up period (G-J).
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F4
In patient 2, MR imaging studies performed in 2006 and in 2012 showed mild worsening of the lesions in the cerebellar peduncles (Figure 4).