Abstract
Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. We aim to evaluate urinary sulphatoxymelatonin as a biomarker of brain serotonin status in a cohort of patients with mutations in genes related to serotonin biosynthesis. We analized urinary sulphatoxymelatonin from 65 healthy subjects and from 28 patients with genetic defects. A total of 18 patients were studied: 14 with autosomal dominant and recessive guanosine triphosphate cyclohydrolase-I deficiency; 3 with sepiapterin reductase deficiency; and 1 with aromatic L-amino acid decarboxylase deficiency. Further 11 patients were studied after receiving serotoninergic treatment (serotonin precursors, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors): 5 with aromatic L-amino acid decarboxylase deficiency; 1 with sepiapterin reductase deficiency; 3 with dihydropteridine reductase deficiency; and 2 with 6-pyruvoyltetrahydropterin synthase deficiency. Among the patients without therapy, 6 presented low urinary sulphatoxymelatonin values, while most of the patients with guanosine triphosphate cyclohydrolase-I deficiency showed normal values. 5 of 11 patients under treatment presented low urine sulphatoxymelatonin values. Thus, decreased excretion of sulphatoxymelatonin is frequently observed in cases with severe genetic disorders affecting serotonin biosynthesis. In conclusion, sulphatoxymelatonin can be a good biomarker to estimate serotonin status in the brain, especially for treatment monitoring purposes.
Highlights
Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine
Yano et al reported that blood melatonin and urine aMT6s levels may serve as biomarkers reflecting brain serotonin synthesis in subjects with phenylketonuria (PKU)[4]
After establishing the reference values (RVs), urine aMT6s was studied in 28 patients with genetic defects affecting serotonin biosynthesis
Summary
Melatonin is synthesized from serotonin and it is excreted as sulphatoxymelatonin in urine. There are several genetic alterations affecting brain serotonin and dopamine biosynthesis (Fig. 1): aromatic L-amino acid decarboxylase (AADC) deficiency (OMIM#608643), pyridoxal phosphate (PLP) deficiency (pyridoxamine 5-phosphate oxidase deficiency, OMIM#610090), antiquitin deficiency (OMIM#266100) and tetrahydrobiopterin (BH4) disorders including the following deficiencies: dominant and recessive form of guanosine triphosphate cyclohydrolase-I (GTPCH-1, OMIM#128230 and OMIM#233910 respectively), 6-pyruvoyltetrahydropterin synthase (PTPS, OMIM#261640), sepiapterin reductase (SR, OMIM#612716), dihydropteridine reductase (DHPR, OMIM#261630) and primapterinuria (OMIM#264070). Other disorders such as tyrosine hydroxylase deficiency and the recently reported transportopathies[5,6] impair dopamine biosynthesis in particular[7]. The symptoms that are thought to be related to serotonin deficiency are more difficult to clinically assess
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