β-Galactosidase deficiency in the GLB1 spectrum of lysosomal storage disease can present with severe muscle weakness and atrophy
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β-Galactosidase deficiency in the GLB1 spectrum of lysosomal storage disease can present with severe muscle weakness and atrophy. / Pedersen, Jonas Jalili; Duno, Morten; Wibrand, Flemming; Hammer, Christian; Krag, Thomas; Vissing, John.
I: JIMD Reports, Bind 63, Nr. 6, 2022, s. 540-545.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - β-Galactosidase deficiency in the GLB1 spectrum of lysosomal storage disease can present with severe muscle weakness and atrophy
AU - Pedersen, Jonas Jalili
AU - Duno, Morten
AU - Wibrand, Flemming
AU - Hammer, Christian
AU - Krag, Thomas
AU - Vissing, John
N1 - Publisher Copyright: © 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - fat replacement
KW - GLB1-related disorders
KW - metabolic neuromuscular disorder
KW - Morquio B
KW - muscle wasting
KW - myopathy
KW - β-galactosidase deficiency
U2 - 10.1002/jmd2.12324
DO - 10.1002/jmd2.12324
M3 - Journal article
C2 - 36341176
AN - SCOPUS:85141723111
VL - 63
SP - 540
EP - 545
JO - JIMD Reports
JF - JIMD Reports
SN - 2192-8304
IS - 6
ER -
ID: 338354433