GTP-cyclohydrolase deficiency responsive to sapropterin and 5-HTP supplementation: relief of treatment-refractory depression and suicidal behaviour.
The authors describe a new variant of guanosine triphosphate (GTP)- cyclohydrolase deficiency in a young man with severe and disabling major depressive disorder with multiple near-lethal suicide attempts. His cerebrospinal fluid levels showed that the concentration of tetrahydrobiopterin (BH4), neopterin, 5-hydroxyindoleacetic acid and homovanillic acid were below the reference range, suggesting a defect in the pterin biosynthetic pathway and in synthesis of dopamine and serotonin indicative of GTP-cyclohydrolase deficiency. Patient was started on sapropterin, a BH4 replacement protein, for the defect in the above pathway. In addition, the authors started 5-hydroxytryptophan titrated to 400 mg orally twice daily with concomittant carbidopa 37.5 mg orally four times a day, and he responded with remission of suicidal ideation and significant improvement in depression and function.
Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA. thomasla@upmc.edu
Lisa
L
Pan
Brian William
BW
McKain
Suneeta
S
Madan-Khetarpal
Marianne
M
Mcguire
Rasim S
RS
Diler
James M
JM
Perel
Jerry
J
Vockley
David A
DA
Brent
D006916:5-Hydroxytryptophan / Q000627:therapeutic use*; D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D006136:GTP Cyclohydrolase / Q000172:deficiency*; D006801:Humans; D008297:Male; D059020:Suicidal Ideation
D018687:Antidepressive Agents, Second-Generation; D001708:Biopterins; D006916:5-Hydroxytryptophan; D006136:GTP Cyclohydrolase; C003402:sapropterin