Table 1.

Main characteristics and outcomes of included studies

First author/year [Ref.]	Study design	No. (M:F)	Presentation	Mean age at mol. Diag (Y)	Country/ethnicity	SS (< 3%)	Parent marriage	Enzyme activity	Liver biopsy	MPS type/panel	Suspected disease	Result of molecular test	Read length	Mean depth of coverage	Type of sequencer	Trio-based test (parents)
Tong et al. [17]	Coh	2 (1:1)	Developmental delay, Hepatosplenomegaly, Dystrophia, Neutropenia,	2.5	China	2 patients	Non-consanguineous	NR	NR	ES/ Exome Sequencing TruSight One Gene Panel	Neurodevelopmental Disease	1 GSD Ia, 1 GSD Ib	2 × 100–150 bp	142×	HiSeq2500 (Illumina)	YES Both parent
Roscher et al. [20]	Coh	21 (17:4)	Hepatomegaly, liver fibrosis and adenoma, mild cardiomyopathy	11.7	Canada	2 patients	Non-consanguineous	YES: 14 patients	YES: 10 patients	TGS/NA	GSD III or GSD VI	11 patients GSD IXa; 3 patients GSD IXb; 3 patients GSD IXc; 4 patients GSD VI	2 × 100 bp	100×	HiSeq2000 (Illumina)	YES both parents
Skakik et al. [23]	Coh	5 M	Hepatomegaly and hypoglycemia	1.3	Serbia	YES	Non-consanguineous	YES	YES	ES/ Exome Sequencing TruSight One Gene Panel	Hepatic GSD	GSD III, VI, IXa as well as in non-GSD associated genes, LIPA and SBDS, responsible for cholesteryl-ester storage disease and Schwachman-Diamond syndrome respectively	2 × 100 bp	100 ×	MiSeq (Illumina)	NO
Vega et al. [7]	Coh	22(13:9)	Hepatomegaly, dysmorphic facies, hypoglycemia, hyperuricemia, hyperlipidemia and kidney failure, hypertransaminasemia,	13.5	Spain	YES	NR	NR	NR	TGS/Metabolic disorders panel (Agilent) ES/ Exome Sequencing TruSight One Gene Panel	GSDs	11 NOT detected by TGS:4 Detected (GSD III, VI, IXb, ALDOB) 18 repeated and detected by ES (1 GSD Ib, 6 GSD III, 7 GSD IXa) as well as in not GSD associated genes, LIPA, CPT2, ANO5, NKX2-5	2 × 250 bp 2 × 250 bp	400× 83.6×	MiSeq (Illumina)	YES parents
Zhang et al. [24]	Coh	17 M	hepatomegaly, growth retardation, and liver dysfunction	9.9	China	7 YES, 10 NO	Non-consanguineous	NO	8 YES, 9 NO	TGS/ GSD panel (Agilent)	GSD IX	17 GSD IXa	2 × 100 bp	100×	HiSeq2000 (Illumina)	NO
Wang et al. [2]	CS	16(9:7)	Hypoglycemia and mild hepatosplenomegaly, lactic acidosis, neutropenia	6.5	USA	YES	15 Non-consanguineous:1 Consanguineous	YES	YES	TGS/ GSD panel (Agilent)	GSDs	8 detected and matched with signs (1 GSD Ia, 2 GSD Ib, 3 GSD III, 2 GSD IXa), 4 detected truly with TES but direct seq. not found mut (1 suspected as GSD Ia, recognized as GSD Ib; 1 suspected as GSD 0 recognized as GSD IXc.; 1 suspected as GSD III recognized as GSD VI; 1 suspected as GSD VI or IX recognized as GSD IXa, 5 suspected as hepatic GSD but NOT detected by TGS	1 × 100 bp	758×	HiSeq2000 (Illumina)	5 YES Both parents, 11 NO
Wang et al. [21]	CS	3 M	Hepatomegaly and hypertriglyceridemia	7.3	USA	NO	Non-consanguineous	NR	NR	ES/NA	Hepatic GSD	3 GSD III	1 × 100 bp	~ 1000×	HiSeq2000 (Illumina)	NO
Choi et al. [19]	CS	2 M	Hepatomegaly, elevated AST and ALT levels, neutropenia	0.83	Korean	YES	Non-consanguineous	YES	YES	ES/NA	GSD I	2 GSD Ib	2 × 150–200 bp	NR	HiSeq2000 (Illumina)	NO
Fahiminiya et al. [18]	CS	1 M	Hepatomegaly, and recurrent hypoglycemia	6	Qatar	YES	Consanguineous	YES	YES	ES/NA	GSD I or III	1 GSD IXc	2 × 100 bp	100×	HiSeq2000 (Illumina)	NO
Rousseau-Nepton et al. [22]	C- series	2 (1:1)	Abdominal distension with hepatomegaly, difficulty walking	1.4	Canada	YES	Non-consanguineous	YES	NO	ES/NA	GSD I or III	2 GSD III	NR	100x	HiSeq2000 (Illumina)	YES Parents and siblings
Yang et al. [25]	C-series	3 M	Increased transaminase, Hepatomegaly, Hypoglycemic	2.8	China	1YES, 2 NO	1Consanguineous, 2 Non-consanguineous	YES	1 YES	TGS/ 300 genes associated with hepatopathy panel	Metabolic liver disorders	3 GSD IXa	NR	100×	HiSeq2500 (Illumina)	YES Parents and siblings

Coh cohort, CS cross-sectional, C-Series case-series, NR not reported, SS short stature, MUT mutation, ES exome sequencing, TGS targeted gene sequencing, NA not associated