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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 sequencinga, gene dosage analysis
  Schicks et al. 2013 [32] Adults with ataxia, EOCD and suspected recessive disease 24 Germany NPC1/NPC2 sequencinga
  Zech et al. 2013 [36] Adults with PD, FTD or PSP 790 Germany HRM followed by NPC1/NPC2 sequencinga
  Nanetti et al. 2017 [33] Adults with suspected HD 18 Italy NPC1/NPC2 sequencinga
  Topcu et al. 2017 [34] Family members of NPC1/NPC2 probands 510 Turkey NPC1/NPC2 sequencinga
  Cupidi et al. 2017 [35] Adults with early-onset ‘dementia-plus’ 50 Italy NPC1/NPC2 sequencinga, gene dosage analysis
  Synofzik et al. 2015 [27] Adolescents/adults with unexplained EOA 96 Germany NPC1/NPC2 (NGS gene panelb)
  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 sequencinga, RFLP analysis
  Wassif et al. 2016 [14] Subjects from 4 WES sequencing projects 17,754c 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 sequencinga
  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 sequencinga
 Polo et al. 2016 [61] Neonates with cholestasis 7 Italy Oxysterols (7-KC, C-triol)
  1. 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