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Natural history of motor neuron disease in adult onset GM2-gangliosidosis: A case report with 25   years of follow-up

View Article: PubMed Central - PubMed

ABSTRACT

An adult with Sandhoff disease presented with pure lower motor neuron phenotype. Twenty years later, he showed signs of upper motor neuron involvement. 25 years from the onset, his muscle weakness slightly worsened but he was fully independent in activities of daily living.

GM2-gangliosidosis can manifest as a motor neuron disease with a slowly progressive course. The correct knowledge of the natural history can be really important to achieve the diagnosis, design new therapies and evaluate clinical trials.

No MeSH data available.


Related in: MedlinePlus

a: Brain TC scan performed when patient was 28 years old. Section at level of deep gray matter didn't show the bilateral symmetric thalamic altered signal typical of the infantile form.b: Electron microscopy of the rectal biopsy at diagnosis showed cytoplasmic membranous bodies in neurones of the myenteric plexus (3000 × magnification).c: Sagittal T1-weighted brain MRI showing a mild cerebellar atrophy at 25th year of follow-up.d–f: Rectal biopsy 25 years after the diagnosis. At ultrastructural level, neuronal inclusions were pleiomorphic, composed of single or multiple layers of concentric outer membranes surrounding inner components of short, straight or curved membranes as well as membranous cytoplasmic bodies (3000 ×, 7000 × and 30,000 X magnification, respectively).
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f0005: a: Brain TC scan performed when patient was 28 years old. Section at level of deep gray matter didn't show the bilateral symmetric thalamic altered signal typical of the infantile form.b: Electron microscopy of the rectal biopsy at diagnosis showed cytoplasmic membranous bodies in neurones of the myenteric plexus (3000 × magnification).c: Sagittal T1-weighted brain MRI showing a mild cerebellar atrophy at 25th year of follow-up.d–f: Rectal biopsy 25 years after the diagnosis. At ultrastructural level, neuronal inclusions were pleiomorphic, composed of single or multiple layers of concentric outer membranes surrounding inner components of short, straight or curved membranes as well as membranous cytoplasmic bodies (3000 ×, 7000 × and 30,000 X magnification, respectively).

Mentions: Electromyography demonstrated signs of denervation in lower limbs, whereas nerve conduction study and brain CT scan were normal (Fig. 1a). Biochemical studies, using the artificial fluorogenic substrate 4-methyl-umbelliferyl-2-deoxy-2-acetamido-b-d-glucopyranoside [2], documented a strongly reduced total Hex activity in leukocytes (13% of normal). Hex A activity with substrate 4-methyl-umbelliferyl-beta-d-N-acetylglucosaminide-sulfate was 108 nmol/mg/h (normal value > 210; range 210–1241). On rectal biopsy, the presence of storage material represented by membranous cytoplasmic bodies was detected in neurons of the myenteric plexus (Fig. 1b). HEXB genetic analysis revealed a compound: ∆5′ deletion and c.C1214T (p.Pro417Leu) missense mutation [10].


Natural history of motor neuron disease in adult onset GM2-gangliosidosis: A case report with 25   years of follow-up
a: Brain TC scan performed when patient was 28 years old. Section at level of deep gray matter didn't show the bilateral symmetric thalamic altered signal typical of the infantile form.b: Electron microscopy of the rectal biopsy at diagnosis showed cytoplasmic membranous bodies in neurones of the myenteric plexus (3000 × magnification).c: Sagittal T1-weighted brain MRI showing a mild cerebellar atrophy at 25th year of follow-up.d–f: Rectal biopsy 25 years after the diagnosis. At ultrastructural level, neuronal inclusions were pleiomorphic, composed of single or multiple layers of concentric outer membranes surrounding inner components of short, straight or curved membranes as well as membranous cytoplasmic bodies (3000 ×, 7000 × and 30,000 X magnification, respectively).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5121317&req=5

f0005: a: Brain TC scan performed when patient was 28 years old. Section at level of deep gray matter didn't show the bilateral symmetric thalamic altered signal typical of the infantile form.b: Electron microscopy of the rectal biopsy at diagnosis showed cytoplasmic membranous bodies in neurones of the myenteric plexus (3000 × magnification).c: Sagittal T1-weighted brain MRI showing a mild cerebellar atrophy at 25th year of follow-up.d–f: Rectal biopsy 25 years after the diagnosis. At ultrastructural level, neuronal inclusions were pleiomorphic, composed of single or multiple layers of concentric outer membranes surrounding inner components of short, straight or curved membranes as well as membranous cytoplasmic bodies (3000 ×, 7000 × and 30,000 X magnification, respectively).
Mentions: Electromyography demonstrated signs of denervation in lower limbs, whereas nerve conduction study and brain CT scan were normal (Fig. 1a). Biochemical studies, using the artificial fluorogenic substrate 4-methyl-umbelliferyl-2-deoxy-2-acetamido-b-d-glucopyranoside [2], documented a strongly reduced total Hex activity in leukocytes (13% of normal). Hex A activity with substrate 4-methyl-umbelliferyl-beta-d-N-acetylglucosaminide-sulfate was 108 nmol/mg/h (normal value > 210; range 210–1241). On rectal biopsy, the presence of storage material represented by membranous cytoplasmic bodies was detected in neurons of the myenteric plexus (Fig. 1b). HEXB genetic analysis revealed a compound: ∆5′ deletion and c.C1214T (p.Pro417Leu) missense mutation [10].

View Article: PubMed Central - PubMed

ABSTRACT

An adult with Sandhoff disease presented with pure lower motor neuron phenotype. Twenty years later, he showed signs of upper motor neuron involvement. 25 years from the onset, his muscle weakness slightly worsened but he was fully independent in activities of daily living.

GM2-gangliosidosis can manifest as a motor neuron disease with a slowly progressive course. The correct knowledge of the natural history can be really important to achieve the diagnosis, design new therapies and evaluate clinical trials.

No MeSH data available.


Related in: MedlinePlus