Rare neurodevelopmental abnormalities of sarcosinemia may involve glycinergic stimulation of a primed N-methyl-d-aspartate receptor.
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.
Deutsch
Stephen I
SI
Mental Health Service Line, Department of Veterans Affairs Medical Center, 50 Irving St, NW, Washington, DC 20422, USA. Stephen.Deutsch@med.va.gov
Rosse
Richard B
RB
Long
Katrice D
KD
Gaskins
Brooke
B
Mastropaolo
John
J
D000592:Amino Acid Metabolism, Inborn Errors / Q000503:physiopathology*; D001921:Brain / Q000002:abnormalities / Q000254:growth & development; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D005998:Glycine / Q000378:metabolism* / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D012521:Sarcosine / Q000378:metabolism*
D050487:Glycine Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine; D012521:Sarcosine