β-Galactosidase deficiency in the GLB1 spectrum of lysosomal storage disease can present with severe muscle weakness and atrophy

Abstract

Deficiency of the enzyme β-galactosidase due to variants in the GLB1-gene is associated with metabolic disorders: Morquio B and GM1-gangliosidosis. Here, we report a case compound heterozygous for variants in the GLB1-gene and a severe muscular phenotype. Full body T1-w MRI was conducted for muscular involvement. Biopsy was stained with hematoxylin and eosin for histopathological evaluation. EDTA blood-sample was subjected to whole exome sequencing. Metabolic analysis included residual enzyme activity and evaluation urinary substrate secretion. Additionally, electroneurography, echocardiography, forced volume capacity and biochemistry were evaluated. Examination showed severe proximal weakness (MRC: hip flexion 2, hip extension 2, and shoulder rotation 2), Gower's sign, no extrapyramidal symptoms and normal creatine kinase levels. MRI showed severe muscle wasting of the thigh and shoulder girdle. Muscle biopsy showed mild myopathic changes. β-galactosidase activity was reduced to 28%-34%. Urinary glycosaminoglycan was elevated by 5.9-8.6 mg/mmol (ref.:0-5.1 mg/mmol). Electrophoresis indicated excess keratan sulfate. Exome sequencing revealed two missense variants in the GLB1 gene. Clinical features, genetic testing and laboratory findings indicate a case of β-galactosidase-deficiency with a muscular phenotype.

Keywords: GLB1‐related disorders; Morquio B; fat replacement; metabolic neuromuscular disorder; muscle wasting; myopathy; β‐galactosidase deficiency.

FIGURE 1

Clinical pictures of the patients back and thigs. (A) Shows scapulae alatae. (B) shows pronounced atrophy of the thigh muscles

FIGURE 2

Full body localizer (left) and T1‐weighted cross‐sectional image (A–F) shows significant fat replacement with a proximal to distal gradient affection. (A) Shoulder girdle (White arrow: fat replacement of subscapularis. Black arrow: atrophy of deltoid muscle. (B) Gluteal muscles (White arrow: fat replacement of gluteus medius and intermedius). (C) Mid‐thigh muscles show severe fat replacement except for rectus, femori, and sartorius. (D) Distal‐thigh muscles with less fat replacement, vastus muscles except for rectus femoris still affected. (E,F) Deep posterior compartment of calves is more affected proximally (arrow E) than distally (arrow F)

FIGURE 3

Histology of a vastus lateralis muscle biopsy demonstrates a mild myopathy with vacuoles and sarcolemmal invaginations. (A) HE stained section demonstrates mild myopathy and vacuoles with occasional central nuclei due to degeneration/regeneration cycle. (B,C) Vacuoles with or without nuclei (white arrows) are evident. Invaginations (white asterisk) are seen as well, occasionally with a nucleus inside the invagination. Bar is 50 μm