Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism

• Verfasst von: Manti, Filippo [VerfasserIn]
• Verfasst von: Nardecchia, Francesca [VerfasserIn]
• Verfasst von: Blau, Nenad [VerfasserIn]
• Titel: Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism
• Verf.angabe: Filippo Manti, Francesca Nardecchia, Sabina Barresi, Martina Venditti, Simone Pizzi, Fadi F. Hamdan, Nenad Blau, Alberto Burlina, Marco Tartaglia, Vincenzo Leuzzi
• Jahr: 2019
• Umfang: 4 S.
• Fussnoten: Available online 11 October 2018 ; Gesehen am 14.08.2019
• Titel Quelle: Enthalten in: Parkinsonism & related disorders
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1995
• Jahr Quelle: 2019
• Band/Heft Quelle: 61(2019), Seite 207-210
• ISSN Quelle: 1873-5126
• DOI: doi:10.1016/j.parkreldis.2018.10.012
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Clathrin
• Sach-SW: Developmental disorders
• Sach-SW: Hyperphenylalaninemia
• Sach-SW: Neurotransmitter disorders
• Sach-SW: Parkinsonism
• Sach-SW: Selegiline
• K10plus-PPN: 1671357027

Abstract

Introduction - Clathrins play a key role in endocytosis, recycling, and trafficking as well as the generation of presynaptic vesicles. We report a new clinical condition associated with a de novo variant in the CLTC gene, which encodes the clathrin heavy polypeptide. - Case report - This 30-year-old woman presented with a developmental disorder during childhood that progressed to mild cognitive decline in late childhood and relapsing-remitting hypokinetic-rigid syndrome with severe achalasia, weight loss, and mood disorder in adulthood. 123I-Ioflupane SPECT was normal. Blood phenylalanine was slightly increased and PAH sequencing revealed compound heterozygosity for two variants, p.[Asp151Glu]:[Thr380Met]. CSF examination unexpectedly detected a remarkable reduction of homovanillic, 5-hydroxyindolacetic, and 5-methylthetrahydrofolic acids, which could not be ascribed to any alteration of tetrahydrobiopterin and related biogenic amine pathways. - Methods - Trio-based exome sequencing was performed. - Result - A de novo missense variant (c.2669C>T/p.Pro890Leu) was detected in CLTC. Treatment with biogenic amine precursors was ineffective, while the inhibitor of MAO-A selegiline resulted in persistent clinical improvement. - Conclusions - We suggest CLTC defect as a new disorder of biogenic amine trafficking, resulting in neurodevelopmental derangement and movement disorder. Neurotransmitter depletion in CSF may be a biomarker of this disease, and selegiline a possible treatment option.