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Table 3 Diagnostic suspicions and biochemical/histopathological tests for patients diagnosed using the NGS-LSD tool

From: Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders

PC AO AD GD NGS-LSD Initial signs Diagnostic suspicions Biochemical-histopathology studies* Other genetic studies*
P1 2Y - 12Y CLN5 Clumsiness, frequent falls, apraxic gait CLN VL; SBIOP + . PPT1, TTP1
P2 4Y - 7Y CLN6 Clumsiness, myoclonic movements GM2, GCL, MLD, Fabry, Schindler, MANSA, MANBA, MPS, CLN EA: HEXA, HEXB, GLA, NAGA, MANBA, MAN2B1, MPS, GALC, ARSA, PPT1, TTP1 MFSD8
P3 3Y - 16Y CLN3 Language regression, school inattention, social isolation CDG, GM1, GM2, GSL, Schindler, GSD II, III, CLN VL; FC; SPA ; EA: GLB1, HEXB, CTSA, NAGA, GAA, AGL; SBIOP + .  
P4 2Y - 23Y CLN7 Language delay, clumsiness CLN SBIOP +; EA: CLN2. CLN1
P5 4Y - 16Y CLN3 Conduct disorder, attention deficit disorder CLN VL +; SBIOP, MBIOP, NBIOP + . PPT1, TTP1, CLN3, CLN5, CLN8
P6 3Y 4Y 7Y MLD Leukodystrophy Spastic paraparesia EA: ARSA +  
P7 1Y - 9Y GM1 Global developmental delay, gait instability CDG; RCCD; INAD MBI; NBIOP +; MBS; SPA; EA: HEXA, HEXB  
P8 2Y 7Y 4Y GM2 Language delay, conduct disorder Unspecific global developmental delay, Neurodegenerative disease; CLN, GM2 SBIOP; MBS; EA: HEXA + . Caryotype; Fragile X; Smith-Magenis
P9 2Y - 14Y GM2 Clumsiness, frequent falls Ataxia, Attention deficit disorder MBI Caryotype; Fragile X; CGH-60 k array.
P10 3Y 9Y 12Y GM1 Clumsiness, frequent falls, language delay RS, MPSIII, GM1 MBS, U-GAGs; EA: GLB1+ Caryotype, Fragile-X, MECP2
P11 5Y - 22Y GM2 Learning problems, language difficulties CLN SBIOP CLN3, CLN8
P12 13Y - 18Y NPC2# Clumsiness, short stature MTDPS; RCCD; SCA; DRPLA MBIOP; RCCFS; EA: muscular Coenzima Q10 mtADN(muscle); MTATP6; tRNALeu(UUR); SCA1,2,3,6,7,12,17; ATN1
P13 18 M - 4Y ML II,III Growth delay, macrocephaly MPS U-GAGs SHOX
P14 12 M 3Y 3Y GM2 Psycomotor regression, language regression RS, GM2 EA: HEXA +, HEXB MECP2
P15 0 M 3 M 1Y GM1 Hypotonia, hepatomegaly, cardiomyopathy, bony abnormalities GSD II EA: GAA  
P16 9 M 2Y 2Y MPSVI Bilateral costal deformity, macrocephaly AA, MPS U-GAGs, Dermatan sulfate in urine, EA: ARSB  
P17 0 M - 2Y ML II,III Hypotonia, microcephaly, jaundice MPS MBS, U-OLG, U-GAGs Caryotype; CGH array
P18 2 M 3Y 6Y MPSII Bilateral inguinal hernia MPS U-GAGs; EA: IDS +  
P19 1Y 4Y 5Y MPSI Clubfoot, arthrogryposis, clawed hands MPS U-GAGs; EA: IDUA +, IDS, ARSB  
P20 0 M 1Y 1Y GM1 Hypotonia, severe psycomotor delay GM1, GM2, GSL, ML I MBS; VL; U-GAGs; EA: GBL1 +, HEXA, HEXB, CTSA, NEU1  
P21 18 M 3Y 3Y GM2 Unsteady gait, frequent falls TORCH, Leukodystrophy EA:  
P22 2Y - 6Y CLN8 Cognitive regression, epilepsy Lennox syndrome, CLN PBIOP +  
P23 3Y - 9Y CLN10 Psycomotor regression, dystonia, epilepsy Neuroaxonal dystrophy, sphingolipidosis MBIO mtDNA
P24 3Y 5Y 23Y MPSIIIB Language delay, conduct disorder, learning disabilities, hypoacusia MPS Heparan sulfate +  
P25 1Y - 6Y GM2AB Developmental delay, regression GM2, GSD II EA: HEXA, HEXB, GAA (+); HPS GM2 + GAA
P26 4Y - 25Y CLN8 Cognitive regression, epilepsy CLN   CLN6
  1. Abbreviations: PC Patient Code, AO Age of Onset (Y: years; M: months; deceased), AD Age at Diagnosis, GD age at Genetic Diagnosis, NGS-LSD diagnosis reached with our NGS tool, CLN Neuronal Ceroid Lipofuscinosis, MLD metachromatic leukodystrophy, GM1 and 2 Gangliosidosis I and II, NPC2 Niemann-Pick disease, type C2, ML II III mucolipidosis III alpha/beta, MPS mucopolysaccharidosis, GM2AB Gangliosidosis type II, AB variant, MANSA Mannosidosis, alpha-, types I and II, MANBA mannosidosis beta, CDG congenital disorder of glycosylation, GSL galactosialidosis, GSD glycogen storage disease, GSD II Pompe disease, RCCD respiratory chain complex deficiency, INAD infantile neuroaxonal dystrophy, RS Rett syndrome, AA autoimmune arthritis, ML I sialidosis, TORCH Band-like calcification with simplified gyration and polymicrogyria, MBS metabolic study, SPA sialotransferrin profile analysis, VL vacuolated lymphocytes in peripheral blood, FC foam cells in bone marrow, RCCFS respiratory chain complex functional studies, GCL globoid cell leukodystrophy or Krabbe disease, SCA spinocerebellar ataxia, EA enzymatic assay, U-GAGs urinary glycosaminoglycan levels, U-OLG urinary oligosaccharides levels, SBIOP skin biopsy, MBIOP muscle biopsy, NBIOP nerve biopsy, HPS pathological study, mtDNA mithocondrial DNA deletions, depletion and punctual mutations, MTDPS mitochondrial depletion syndrome, CGH comparative genomic hybridization; #: not confirmed; *All results were negative unless indicated by a plus sign.