The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

Glycine is a major neurotransmitter that activates inhibitory glycine receptors and is a co-agonist for excitatory glutamatergic N-methyl-D-aspartate (NMDA) receptors. Two transporters, GLYT1 and GLYT2, regulate extracellular glycine concentrations within the CNS. Dysregulation of the extracellular glycine has been associated with hyperekplexia and nonketotic hyperglycinemia. Here, we report four individuals from two families who presented at birth with facial dysmorphism, encephalopathy, arthrogryposis, hypotonia progressing to hypertonicity with startle-like clonus, and respiratory failure. Only one individual survived the respiratory failure and was weaned off ventilation but has significant global developmental delay. Mildly elevated cerebrospinal fluid (CSF) glycine and normal serum glycine were observed in two individuals. In both families, we identified truncating mutations in SLC6A9, encoding GLYT1. We demonstrate that pharmacologic or genetic abolishment of GlyT1 activity in mice leads to mildly elevated glycine in the CSF but not in blood. Additionally, previously reported slc6a9-null mice and zebrafish mutants also display phenotypes consistent with the affected individuals we examined. Our data suggest that truncating SLC6A9 mutations lead to a distinct human neurological syndrome hallmarked by mildly elevated CSF glycine and normal serum glycine.

The amino acid glycine acts as a neurotransmitter at both inhibitory glycinergic and excitatory glutamatergic synapses predominantly in caudal regions of the central nervous system but also in frontal brain regions and the retina. After its presynaptic release and binding to postsynaptic receptors at caudal glycinergic synapses, two high-affinity glycine transporters GlyT1 and GlyT2 remove glycine from the extracellular space. Glycinergic neurons express GlyT2, which is essential for the presynaptic replenishment of the transmitter, while glial-expressed GlyT1 was shown to control the extracellular glycine concentration. Here we show that GlyT1 expressed by glycinergic amacrine cells of the retina does not only contribute to the control of the extracellular glycine concentration in the retina but is also essential for the maintenance of the glycinergic transmitter phenotype of this cell population. Specifically, loss of GlyT1 from the glycinergic AII amacrine cells impairs AII-mediated glycinergic neurotransmission and alters regulation of the extracellular glycine concentration, without changes in the overall distribution and/or size of glycinergic synapses. Taken together, our results suggest that GlyT1 expressed by amacrine cells in the retina combines functions covered by neuronal GlyT2 and glial GlyT1 at caudal glycinergic synapses.

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