Audrey Thurm1, Cristan Farmer1, Nicole Yanjanin Farhat2, Edythe Wiggs3, David Black1, Forbes D Porter2. 1. Pediatrics and Developmental Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, NIH, DHHS, Bethesda, MD, USA. 2. Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, Bethesda, MD, USA. 3. National Human Genome Research Institute, National Institute of Mental Health, NIH, DHHS, Bethesda, MD, USA.
Abstract
AIM: To describe the neurocognitive and adaptive behavior profile of children and adolescents with Niemann-Pick Disease type C1 (NPC1), a rare genetic disease that frequently presents in childhood, with variable onset and symptom complex involving neurodegeneration. METHOD: Thirty-eight participants (20 males, 18 females; mean age 8y 10mo, SD 4y 8mo, range 1-18y) with NPC1 were evaluated through a natural history protocol. RESULTS: NPC1 severity was in the mild to moderate range for most participants. Cognitive scores (n=32) ranged from very low to above average; about half of the participants exhibited a clinically significant advantage of Verbal IQ over Non-verbal IQ. Adaptive behavior scores (n=21) were generally in the borderline to impaired range. Longitudinal cognitive data (n=19) suggested a pattern of decreasing scores over time. However, most participants remained at the same general level of functioning throughout the study. INTERPRETATION: This study begins to systematically describe the neurocognitive phenotype of children and adolescents with NPC1, identifying heterogeneity and decline, aiding in understanding the natural history of the disease to plan treatment studies. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
AIM: To describe the neurocognitive and adaptive behavior profile of children and adolescents with Niemann-Pick Disease type C1 (NPC1), a rare genetic disease that frequently presents in childhood, with variable onset and symptom complex involving neurodegeneration. METHOD: Thirty-eight participants (20 males, 18 females; mean age 8y 10mo, SD 4y 8mo, range 1-18y) with NPC1 were evaluated through a natural history protocol. RESULTS:NPC1 severity was in the mild to moderate range for most participants. Cognitive scores (n=32) ranged from very low to above average; about half of the participants exhibited a clinically significant advantage of Verbal IQ over Non-verbal IQ. Adaptive behavior scores (n=21) were generally in the borderline to impaired range. Longitudinal cognitive data (n=19) suggested a pattern of decreasing scores over time. However, most participants remained at the same general level of functioning throughout the study. INTERPRETATION: This study begins to systematically describe the neurocognitive phenotype of children and adolescents with NPC1, identifying heterogeneity and decline, aiding in understanding the natural history of the disease to plan treatment studies. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
Authors: P I Dickson; A R Pariser; S C Groft; R W Ishihara; D E McNeil; D Tagle; D J Griebel; S G Kaler; J W Mink; E G Shapiro; K J Bjoraker; L Krivitzky; J M Provenzale; A Gropman; P Orchard; G Raymond; B H Cohen; R D Steiner; S F Goldkind; R M Nelson; E Kakkis; M C Patterson Journal: Mol Genet Metab Date: 2010-12-02 Impact factor: 4.797
Authors: Nicole M Yanjanin; Jorge I Vélez; Andrea Gropman; Kelly King; Simona E Bianconi; Sandra K Conley; Carmen C Brewer; Beth Solomon; William J Pavan; Mauricio Arcos-Burgos; Marc C Patterson; Forbes D Porter Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2010-01-05 Impact factor: 3.568
Authors: F A Wijburg; F Sedel; M Pineda; C J Hendriksz; M Fahey; M Walterfang; M C Patterson; J E Wraith; S A Kolb Journal: Neurology Date: 2012-04-18 Impact factor: 9.910
Authors: Sue Ramsden; Fiona M Richardson; Goulven Josse; Michael S C Thomas; Caroline Ellis; Clare Shakeshaft; Mohamed L Seghier; Cathy J Price Journal: Nature Date: 2011-10-19 Impact factor: 49.962
Authors: Elizabeth Berry-Kravis; Jamie Chin; Anne Hoffmann; Amy Winston; Robin Stoner; Lisa LaGorio; Katherine Friedmann; Mariana Hernandez; Daniel S Ory; Forbes D Porter; Joan A O'Keefe Journal: Pediatr Neurol Date: 2018-01-08 Impact factor: 3.372
Authors: Charlotte DiStefano; Rujuta B Wilson; Carly Hyde; Edwin H Cook; Ronald L Thibert; Lawrence T Reiter; Vanessa Vogel-Farley; Joerg Hipp; Shafali Jeste Journal: Am J Med Genet A Date: 2019-10-26 Impact factor: 2.802
Authors: Banshi Lal Kumawat; Pankaj Kumar Saini; Chandra Mohan Sharma; Manisha Sharma; L S Manu Journal: Ann Indian Acad Neurol Date: 2019-10-25 Impact factor: 1.383
Authors: Eugen Mengel; Bruno Bembi; Mireia Del Toro; Federica Deodato; Matthias Gautschi; Stephanie Grunewald; Sabine Grønborg; Bénédicte Héron; Esther M Maier; Agathe Roubertie; Saikat Santra; Anna Tylki-Szymanska; Simon Day; Tara Symonds; Stacie Hudgens; Marc C Patterson; Christina Guldberg; Linda Ingemann; Nikolaj H T Petersen; Thomas Kirkegaard; Christine Í Dali Journal: Orphanet J Rare Dis Date: 2020-11-23 Impact factor: 4.123
Authors: Elise Riquin; Magalie Barth; Thomas Le Nerzé; Natwin Pasquini; Clement Prouteau; Estelle Colin; Patrizia Amati Bonneau; Vincent Procaccio; Patrick Van Bogaert; Philippe Duverger; Dominique Bonneau; Arnaud Roy Journal: Front Psychiatry Date: 2022-04-07 Impact factor: 4.157