CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.
Low sialic acid in spinal fluid flagged GM2 gangliosidosis in a teen with sudden skill loss, showing sugar chains can reveal the real cause of regression.
01Research in Context
What this study did
Doctors took spinal fluid from a high-school boy. The boy had GM2 gangliosidosis and was losing words and skills fast.
They checked the sugar chains on his spinal-fluid proteins. This is called CSF glycan profiling.
What they found
The boy was missing sialic acid on many proteins. Sialic acid helps brain cells talk.
The missing sugar could explain why he slid into childhood disintegrative disorder.
How this fits with other research
Munce et al. (2010) saw the same low-sialic pattern in plasma from kids with Prader-Willi syndrome. Both studies use glycan tests to spot sugar problems hiding behind autism traits.
Almatrafi et al. (2023) also ran metabolic screens and found a different defect in two brothers with ASD. Together the papers warn: check metabolism before calling it "just autism."
Cohrs et al. (2017) reviewed Sanfilippo syndrome and showed speech loss plus ASD features are common in metabolic disease. Barone et al. (2016) adds GM2 gangliosidosis to that same warning list.
Why it matters
If a teen on your casetable suddenly loses language, ask the doctor about metabolic screening. A simple spinal-fluid sugar test could reveal GM2 gangliosidosis. Early diagnosis lets the family join gene-therapy trials and stops you from writing off the regression as "autism behavior."
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02At a glance
03Original abstract
Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS.
Autism research : official journal of the International Society for Autism Research, 2016 · doi:10.1002/aur.1541