GM1gangliosidosis: Clinical and radiological clue to diagnosis.

GM1gangliosidosis is a rare autosomal recessive lysosomal storage disorder caused by deficiency of enzyme β-galactosidase, resulting in progressive neural and visceral accumulation of GM1gangliosides. Coarse facial features, bilateral cherry red spots, and dysostosis multiplex are important clue to diagnose this condition. We describe a case of GM1gangliosidosis with dysostosis multiplex and characteristic magnetic resonance imaging findings.

Introduction

Lysosomal storage disorders are rare disorders caused by genetically transmitted lysosomal enzyme deficiencies. Classic neuroimaging findings described in GM2 gangliosidosis is hyperdense signal in bilateral thalami in non-contrast computed tomography (NCCT) scan and hypointensity in T2 weighted MRI images. Similar neuroimaging findings can be seen in other lysosomal storage disorders also. Hyperdens thalamus in NCCT head in a child with neuroregrssion, facial dysmorphism and organomegaly, should lead us to think about GM1 gangliosidosis.

Clinical Profile

A 16-month-old girl presented with history of regression of mile stones for last 6 months. Psychomotor development was normal until 12 months of age; subsequently, she gradually lost ability to sit, neck control, and social smile. She had attained vocabulary of single syllable by 1 year, but subsequently lost it. There was no history of seizures. Child was born of a nonconsanguineous marriage; there was no adverse perinatal event. There was no significant family history. On examination, she had coarse facies, horizontal nystagmus, hepatosplenomegaly, and multiple mongolian spots [Figure 1]. On fundus examination, she had bilateral macular cherry red spots [Figure 2]. Skeletal survey revealed dysostosis multiplex at dorsolumbar junction, as superiorly notched (inferiorly beaked) vertebral bodies in the lateral view at the thoracolumbar junction [Figure 3]. Clinical diagnosis of GM1gangliosidosis was supported with MRI brain findings and confirmed with absence of β-galactosidase enzyme activity in leukocytes [Figure 4].

Figure 1

Clinical pictures of a 16-month-oldgirl showing massive hepatosplenomegaly, excessive mongolian spots, and severe failure to thrive

Figure 2

Photograph of retina in patient with GM1gangliosidosis showing cherry red spot and optic disc edema

Figure 3

X-ray of same patient showing dysostosis multiplex at lumbar spine and NCCT scan of brain (axial sections) at level of thalamus showing bilateral hyperdense thalamus

Figure 4

AxialT1-weighted image and T2-weighted image at the level of thalamus show diffuse dysmyelination of white matter with bilaterally symmetric thalamic signal change, which appear hyperintense on T1-weighted and hypointense on T2-weighted images

Discussion

GM1gangliosidosis is a rare autosomal recessive lysosomal storage disorder caused by deficiency of lysosomal enzyme β-galactosidase, resulting in progressive neural and visceral accumulation of GM1gangliosides, its asialo derivative GA1, and other minor glycolipids and glycopeptides. Three clinical phenotypes can be distinguished and classified by age of onset: Infantile, late infantile/juvenile, and adult. The age of onset and rate of progression of the disease depend on the residual activity of enzyme β-galactosidase. Infantile GM1gangliosidosis, the most common and severe form, is characterized by facial and skeletal abnormalities and neurological deterioration before the age of 6 months. Death usually occurs before the second birthday.[1] This disorder can be diagnosed by several ways, including lysosomal enzyme assay of low β-galactosidase activity in peripheral blood leukocytes or cultured skin fibroblasts, detection of abnormal urinary oligosaccharide excretion, and rectal biopsy. Prenatal diagnosis by measurement of enzyme activity in amniotic fluid and cultivated amniotic fluid cells has also been established.

The classic neuroimaging findings in patients with infantile GM1gangliosidosis include thalamic hyper density on non contrast computed tomography (NCCT) scan and hypointense signal of the thalami with persistent high signal intensity of the white matter on T2-weighted images, indicating severely defective myelination[1-3] [Figure 4]. Significant white matter abnormalities are present only in the infantile form of GM1gangliosidosis, but they are also described in other infantile-onset neuronal storage disorders, such as GM2gangliosidosis and infantile neuronal ceroid lipofuscinosis.[2] A paucity of myelin in GM1gangliosidosis has been demonstrated by several classical neuropathologic and neuroimaging studies of patients and animal models.[34]