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case_images: Physical and imaging examination of the patient (Case 1). (A) Physical examination showed the right gastrocnemius muscle was slightly thinner compared to the left side. Flexion deformities in the interphalangeal joints of the distal toes (yellow arrow) in both feet, and elevated arches (red arrow) in right feet. (B) Anteroposterior and lateral x-ray images of both ankle joints (weight-bearing). The results of x-ray of ankle joints revealed elevated arches (red arrow) in right feet and flexion deformities of the distal interphalangeal joints in both feet (yellow arrow). (C) Brain MRI (T2W) revealed symmetrical strip-like abnormal signals (yellow arrow) in the corticospinal tract, suggestive of demyelinating changes. The images are shown in coronal (left) and axial (right) views.
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case_images: Physical examination revealed a slightly thinner right gastrocnemius muscle compared to the left, flexion deformities of the distal interphalangeal joints in both feet, and elevated arches in both feet (Figure 1A). Bilateral ankle x-rays (standing position) revealed: (1) elevated right foot arch and (2) flexion deformities of the distal interphalangeal joints in both feet (Figure 1B). Brain MRI revealed signs of demyelination (Figure 1C).
case_images: Muscle biopsy pathology of the patient's right fibular muscle. (A-C) H&E staining. The results showed small clusters of muscle atrophy (indicated by the yellow box), with the formation of nuclear chains (yellow arrows) and angulated muscle fibers (yellow circle). There was no significant proliferation of fibrous or adipose tissue, and no marked infiltration of inflammatory cells. These findings were consistent with neurogenic muscle atrophy. Considering the clinical context, the possibility of peroneal muscular atrophy could not be ruled out. (D-F) Electron microscope images, which revealed mild focal tearing and dissolution of myofibrils, with a slight increase in lipid droplets between individual myofibrils and sub-sarcolemmal regions of some muscle cells.
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case_images: A muscle biopsy of the right lower leg showed clustered muscle atrophy, nuclear chains, and angulated fibers (Figure 2), consistent with neurogenic atrophy, raising the possibility of Charcot-Marie-Tooth disease (CMT).
case_images: Brain MRI (T2W) of the patient's sister (Case 2). The MRI revealed symmetrical strip-like abnormal signals (yellow arrow) in the periventricular region and corticospinal tract, suggestive of demyelinating changes. Enlargement of the bilateral lateral ventricles, third ventricle, suprasellar cistern, ambient cistern, prepontine cistern, and bilateral cerebellopontine angle cisterns was also observed. The images are shown in coronal (left) and axial (right) views.
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case_images: A brain MRI revealed symmetric strip-like abnormal signals in the bilateral thalamus and corona radiata, and enlargement of the bilateral lateral ventricles, third ventricle, suprasellar cistern, ambient cistern, pre-pontine cistern, and bilateral cerebellopontine angle cisterns (Figure 3), suggestive of "demyelination disease." Additionally, she experienced severe headaches, and during intense episodes, she had experienced confusion and urinary and fecal incontinence, with cognitive decline following recovery.
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case_images: Pedigree chart and genetic testing results of the family. (A) Pedigree chart (autosomal recessive inheritance pattern). (B-F) Genetic testing results. The results indicated that the patient (Case 1) and her sister (Case 2) carried a missense mutation on chromosome 14 in the GALC gene: NM_000153.4(GALC).1901T>C (p.Leu634Ser) (Reference genome version Human GRCH37/hg19), a homozygous variant inherited from both parents. Her parents and brother were heterozygous for the mutation.
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case_images: The pedigree chart and genetic testing results of the family are displayed in Figure 4.
case_images: Prediction of functional effect using PolyPhen-2. The prediction scores for both HumDiv and HumVar were 1.00, which indicating a very high probability to affect GALC protein structure and function.
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case_images: We used PolyPhen-2 software (Adzhubei et al. ) to predict the pathogenicity of GALC missense variant p.Leu634Ser (Figure 5).