Rare neurodevelopmental abnormalities of sarcosinemia may involve glycinergic stimulation of a primed N-methyl-d-aspartate receptor.

Abstract:

:Sarcosinemia is a relatively rare autosomal recessive disorder that has a varied phenotypic presentation; rarely, it is associated with neurodevelopmental and neurological abnormalities. Sarcosine is a key intermediate in 1-carbon metabolism, and its elevation in blood and urine could reflect a deficient pool size of activated 1-carbon units. Sarcosine is also an inhibitor of an important glycine transporter in brain and is under clinical investigation as a glycinergic intervention for conditions with presumed N-methyl-d-aspartate (NMDA) receptor hypofunction, such as schizophrenia. Preclinical research with a mouse model that is used to study pharmacological modulation of endogenous NMDA receptor-mediated tone may clarify, at least in some instances, varied phenotypic presentations of sarcosinemia that are often clinically benign. Sarcosine's effectiveness as a glycinergic agonist intervention for NMDA receptor hypofunction depends on an interaction between genetic background and a stressful environmental insult. Thus, neurodevelopmental and neurological abnormalities may manifest rarely in sarcosinemia in the context of relatively unique genetic factors and fetal insult or stress.

journal_name

Clin Neuropharmacol

authors

Deutsch SI,Rosse RB,Long KD,Gaskins B,Mastropaolo J

doi

10.1097/01.WNF.0000236767.46526.1F

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

361-3

issue

6

eissn

0362-5664

issn

1537-162X

pii

00002826-200611000-00009

journal_volume

29

pub_type

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