Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?

Sobrido, María-Jesús; Bauer, Peter; de Koning, Tom; Klopstock, Thomas; Nadjar, Yann; Patterson, Marc C; Synofzik, Matthis; Hendriksz, Chris J

doi:10.1186/s13023-018-0985-1

Orphanet Journal of Rare Diseases

Table 2 Summary of published screening studies grouped by screening design

From: Recommendations for patient screening in ultra-rare inherited metabolic diseases: what have we learned from Niemann-Pick disease type C?

Cohort (reference)	Study population	N	Region/country	Primary screening method(s)
Prospective patient screening studies
Genetic screening
Bauer et al. 2013 [31]	Adults with neurological/psych. Symptoms	250	EU and US	NPC1/NPC2 sequencing^a, gene dosage analysis
Schicks et al. 2013 [32]	Adults with ataxia, EOCD and suspected recessive disease	24	Germany	NPC1/NPC2 sequencing^a
Zech et al. 2013 [36]	Adults with PD, FTD or PSP	790	Germany	HRM followed by NPC1/NPC2 sequencing^a
Nanetti et al. 2017 [33]	Adults with suspected HD	18	Italy	NPC1/NPC2 sequencing^a
Topcu et al. 2017 [34]	Family members of NPC1/NPC2 probands	510	Turkey	NPC1/NPC2 sequencing^a
Cupidi et al. 2017 [35]	Adults with early-onset ‘dementia-plus’	50	Italy	NPC1/NPC2 sequencing^a, gene dosage analysis
Synofzik et al. 2015 [27]	Adolescents/adults with unexplained EOA	96	Germany	NPC1/NPC2 (NGS gene panel^b)
Marelli et al. 2016 [40]	Adolescents/adults with probable EOA	33	France	NPC1/NPC2 (NGS gene panel)
Pyle et al. 2015 [41]	Adult patients with inherited and sporadic ataxias	35	UK	NPC1/NPC2 sequencing (WES)
McKay et al. 2014 [42]	Infants with jaundice/cholestasis	228	UK	NPC1/NPC2 sequencing (WES)
Herbst et al. 2015 [43]	Infants with jaundice/cholestasis	6	Germany	NPC1/NPC2 sequencing (NGS gene panel)
Mavridou et al. 2014 [70]	Family members of NP-C patients	153	Greece	NPC1/NPC2 sequencing^a, RFLP analysis
Wassif et al. 2016 [14]	Subjects from 4 WES sequencing projects	17,754^c	International	Historical WES + WES from public databases
Blood biomarker screening
Reunert et al. 2016 [44]	Patients with suspected NP-C	1800	Germany	Oxysterol level (C-triol)
Ribas et al. 2016 [45]	Patients with suspected NP-C	122	Brazil	Oxysterol level (C-triol), ChT
Zhang et al. 2014 [46]	Children/adults with cholestasis, HSL or psychomotor regression/retardation	302	China	Oxysterol level (7-KC)
De Castro et al. 2017 [47]	Patients with suspected NP-C	236	Spain	ChT, CCL18/PARC, NPC1/NPC2 sequencing^a
Sheth et al. 2014 [48]	Children with possible LSDs	1110	India, Sri Lanka, Afghanistan	Urine GAGs, plasma ChT, enzyme activity
Studies based on archived (biobank) samples
Cebolla et al. 2015 [50]	Patients with NP-C	97	Spain	Oxysterol level (7-KC)
Studies based on patient file and clinical chart review
Yerushalmi et al. 2002 [51]	Neonates with jaundice/cholestasis	40	US	Medical chart review
Hegarty et al. 2015 [52]	Children with acute liver failure	127	UK	Clinical, laboratory, and outcome analysis
Verity et al. 2010 [53]	Children with early cognitive impairment	2636	UK	Clinical case surveillance
Winstone et al. 2017 [54]	Children with intellectual and neurological deterioration	3979	UK	Clinical case surveillance
Corry 2014 [55]	Ethnic subjects with suspected autosomal recessive conditions	13,000	UK	Clinical case surveillance
Studies based on newborn screening
Pinto et al. 2004 [60]	Antenatal patients with suspected LSDs	353	Portugal	NPC1/NPC2 sequencing^a
Polo et al. 2016 [61]	Neonates with cholestasis	7	Italy	Oxysterols (7-KC, C-triol)

^aSanger sequencing; ^bMini-exome sequencing of ̴5,000 genes; ^cWES of 17,754 chromosomes. ChT chitotriosidase, CNV copy-number variation, EOA early-onset ataxia, EOCD early-onset cognitive decline, FTD frontotemporal dementia, GAG glycosaminoglycans, HRM high resolution melting, HSL hepatosplenomegaly, LSD lysosomal storage disease, NGS next-generation sequencing, PD Parkinson’s disease, PSP progressive supranuclear gaze palsy, Psych. psychiatric, RFLP restriction fragment length polymorphism, WES whole-exome sequencing

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ISSN: 1750-1172

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