Background
Methods
Results
Disease category | Number of cases diagnosed | Incidence per 100,000 | Mean age at diagnosis | Median age at diagnosis | Range of age |
---|---|---|---|---|---|
Organic acidemias | 34 | 30 | 1.8 years | 60 days | 1 day–10 years |
Propionic acidemia | 9 | 30.2 days | 20 days | 1 day–6 months | |
Methylmalonic acidemia | 7 | ||||
Mutase deficiency | 5 | ||||
Cobalamin A defect | 1 | ||||
Cobalamin C defect | 1 | ||||
Glutaric acidemia | 3 | ||||
3-hydroxy-3-methylglutaryl-CoA lyase deficiency | 4 | ||||
3-Methylcrotonylco A carboxylase deficiency | 3 | ||||
Biotinidase deficiency | 3 | ||||
3-Methylglutaconic Aciduria Type III | 1 | ||||
Ethylmalonic encephalopathy | 1 | ||||
B-ketothiolase deficiency | 1 | ||||
Isovaleric acidemia | 1 | ||||
Malonic aciduria | 1 | ||||
Aminoacidopathies | 30 | 27 | 3.3 years | 10.5 months | 1 day–13 years |
Homocystinuria | 14 | 7 years | 7.5 years | ||
• Classical | 11 | ||||
• MTHFR deficiency | 2 | ||||
• MAT deficiency | 1 | ||||
PKU | 5 | ||||
• Classical | 3 | ||||
• Non-PKU hyperphenylalaninemia | 2 | ||||
Biopterin Synthesis Defect PTPS deficiency | 4 | ||||
MSUD | 5 | ||||
Asparagine synthetase deficiency | 2 | ||||
Vitamins responsive disorders | 18 | 16 | 5.7 years | 5.5 years | 6 months–10 years |
Biotin Thiamine Responsive Basal Ganglia Disease | 17 | ||||
Pyridoxine-dependent epilepsy | 1 | ||||
Inborn Errors of Carbohydrates | 12 | 11 | 3.1 years | 1.3 years | 1 week–7 years |
Galactosemia | 4 | ||||
Transaldolase deficiency | 6 | ||||
Hereditary fructose intolerance | 1 | ||||
Fructose 1,6 bisphosphatase deficiency | 1 | ||||
Urea Cycle Disorders | 12 | 11 | 12 days | 7 days | 1 day–30 days |
Argininosuccinic Aciduria | 8 | ||||
Citrullinemia | 4 | ||||
Fatty Acid Oxidation Defects | 5 | 4 | 1.4 years | 2 days | 2 days–7 years |
VLCAD deficiency | 3 | 21 days | 2 days | 2 days–60 days | |
MCAD deficiency | 1 | 2 days | 2 days | 2 days | |
Carnitine uptake defect | 1 | 7 years | 7 years | 7 years | |
Aminoacids transport defect | 5 | 4 | 10 years | 11 years | 6–13 years |
Cystinuria | 5 | ||||
Metal transport defect | 2 | 2 | 8.5 years | 8.5 years | 7–10 years |
Wilson disease | 2 | ||||
Disorders of Haem biosynthesis | 2 | 2 | 12.5 years | 12.5 years | 12–13 years |
Acute intermittent porphyria | 2 | ||||
Cholesterol biosynthesis defect | 1 | 1 | 1 year | 1 year | 1 year |
CHILD syndrome | 1 | ||||
Total | 121 | 109 | 3.3 years | 9 months | 1 day–13 years |
Disease category | Number of cases diagnosed | Incidence per 100,000 | Mean age at diagnosis | Median age at diagnosis | Range of age |
---|---|---|---|---|---|
Lysosomal Storage Diseases (LSD) | 41 | 37 | 3.6 year | 3 years | 2 months–13 years |
Sphingolipidosis | 22 | 20 | 3.1 years | 2 years | 2 months–13 years |
Fabry disease | 3 | ||||
Sandhoff disease | 2 | ||||
Niemann–Pick disease type B | 1 | ||||
Niemann–Pick disease type C | 3 | ||||
GM1 gangliosidosis (infantile phenotype) | 4 | ||||
Metachromatic leukodystrophy | 3 | ||||
Saposin B Deficiency | 2 | ||||
Krabbe disease | 1 | ||||
Mucopolysaccharidosis (MPS) | 15 | 14 | 5 years | 5 years | 5 months–12 years |
MPS I | 1 | ||||
MPS II | 1 | ||||
MPS IIIA | 2 | ||||
MPS IVA | 5 | ||||
MPS VI | 6 | ||||
Oligosaccharidosis | 2 | 2 | 3 years | 3 years | 2–4 years |
Mucolipidosis II | 1 | ||||
α-mannosidosis | 1 | ||||
Others | |||||
Neuronal ceroid-lipofuscinoses | 3: 2 type 6, and 1 type 8 | 5.3 | 5 | 5–6 years | |
GSD II | 2 | 3.1 months | 3.1 months | 1 week to 6 months | |
Glycogen storage diseases (GSD) | 5 | 4 | 2.2 years | 2 years | 15 months–4 years |
GSD III | 1 | ||||
GSD IV | 1 | ||||
GSD IX | 3 | ||||
Mitochondrial disorders | 12 | 11 | 2.2 years | 8 months | 1 week–8 years |
Leigh disease | 3 | ||||
Pyruvate dehydrogenase deficiency | 2 | ||||
Pyruvate carboxylase deficiency | 2 | ||||
Mitochondrial DNA depletion syndrome 3 | 1 | ||||
Mitochondrial DNA depletion syndrome 5 | 1 | ||||
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 | 1 | ||||
3-Methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like | 1 | ||||
Primary Coenzyme Q10 deficiency type 5 | 1 | ||||
Peroxisomal disorders | 7 | 6 | 2 years | 9 months | 1 week–8 years |
Primary hyperoxaluria type 1 | 5 | ||||
Zellweger syndrome | 1 | ||||
Rhizomelic Chondrodysplasia Punctata | 1 | ||||
Congenital disorders of glycosylation (CDG) | 1 (CDG 1 L) | 1 | 8 years | 8 years | 8 years |
Total | 66 | 60 | 3.1 years | 2 years | 1 week–13 years |
Disease category | Disease | Gene | Reported mutations | Novel mutations | Founder Vs. Private | Type of mutation |
---|---|---|---|---|---|---|
Organic acidemias | Propionic acidemia |
PCCA
| c.425G > A(p. Gly142Asp) | Founder | Homozygous, missense | |
c.350G > A (p.Gly117Asp) | Private | |||||
PCCB
| c.1050dupT | Private | Dupplication | |||
Methylmalonic acidemia |
MUT
| c.329 A > G(p. Tyr110Cys) | Founder | Homozygous, missense, | ||
c.1677-1G > C | Private | Splice | ||||
Cobalamin A Defect |
MMAA
| c.586C > T (p.Arg196*) | Private | Nonsense | ||
Cobalamin C defect |
MMACHC
| c.394C > T (p. Arg132*) | Private | Nonsense | ||
Glutaric acidemia |
GCDH
| c.1144G > A (p.Ala382Thr) | Private | missense | ||
c.853-2A > G (IVS8-2A > G) | Private | Splice | ||||
c.278A > G (p.His93Arg) | Private | missense | ||||
3-hydroxy-3-methylglutaryl-CoA lyase deficiency |
HMGCL
| c.122G > A | Founder | missense | ||
3-Methylcrotonyl CoA carboxylase deficiency |
MCCC1
| c.1808 dup A(p. p.Asn603 Lysfs*5) | Private | Homozygous, duplication | ||
MCCC2
| c.1147A > T (p.Lys383*) | Private | Nonsense | |||
Biotinidase deficiency |
BTD
| c.755A > G (p.Asp252Gly) c.1330G > C (p.Asp444His) | Private | Two heterozygous missense mutations in Exon 4 | ||
3-Methylglutaconic aciduria type III |
OPA3
| c.194delG(p. Gly65Alafs*7) | Private | Homozygous, deletion | ||
Ethylmalonic encephalopathy |
ETHE1
| c.263 C > T(p. Ser88Leu) | Private | Homozygous, missense | ||
B-Ketothiolase deficiency |
ACAT1
| c.412-419del(p. Gln138Tyrfs*36) | Private | Homozygous, deletion | ||
Isovaleric acidemia |
IVD
| c.358C > T(p. Arg120X) | Private | Homozygous, nonsense | ||
Malonyl-CoA decarboxylase deficiency |
MLYCD
| c.953_954delAG(p. Glu318Valfs*35) | Private | Homozygous, deletion | ||
Aminoacidopathies | Homocystinuria | |||||
Classical |
CBS
| c.969G > A (p.Trp323Ter) | Founder | Homozygous missense | ||
c.1006C > T (p.Arg336Cys) | Founder | Homozygous missense | ||||
MTHFR deficiency |
MTHFR
| c.680C > T (p.Thr227Met) | Private | |||
MAT deficiency |
MAT1A
| c.1081G > T(p.Val361Phe) | Private | Homozygous, missense | ||
PKU |
PAH
| c.1169A > G (p.Glu390Gly) | Private | Homozygous, missense | ||
PTPS deficiency |
PTPS
| c.238A > G(p. Met80Val) | Founder | Homozygous, missense | ||
c.169_171delGTG (p.Val57del) | Founder | Homozygous, deletion | ||||
MSUD |
BCKDHA
| c.347A > G(p. Asp116Gly) | Private | missense | ||
c.905A > C (p.Asp302Ala) | Founder | missense | ||||
BCKDHB
| c.674 T > C(p.Leu225Pro) | Private | missense | |||
c.1144 T > C(p.Cys382Arg) | Private | Homozygous, missense | ||||
Asparagine synthetase deficiency |
ASNS
| c.1160A > G (p.Tyr377Cys) | Founder | Homozygous, missense | ||
Vitamins responsive disorders | Biotin Thiamine Responsive Basal Ganglia Disease |
SLC19A3
| c.1264A > G (p.Thr422Ala) | Founder | Homozygous, missense | |
Pyridoxine-dependent epilepsy |
ALDH7A1
| c.877dupAA (p.Ser293Lysfs*22) | Private | Duplication | ||
Inborn Errors of Carbohydrates | Galactosemia |
GALT
| c.691 C > T (p.Arg231Cys) | Founder | Homozygous, missense | |
c.404C > T (p.Ser135Leu) | Private | Homozygous, missense | ||||
c.563A > G (P.Gln188Arg) | Private | Homozygous, missense | ||||
Transaldolase Deficiency |
TALDO1
| c.793delC (p.Gln265ArgfsX56) | Founder | Deletion | ||
Hereditary fructose intolerance |
ALDOB
| c.360_363delCAAA (p.Asn119LysfsX31) | Private | Deletion | ||
Fructose 1,6 bisphosphatase deficiency |
FBP1
| c.114_119dup (p. Cys39_Thr40dup) | Private | Duplication | ||
Urea cycle disorders | Argininosuccinic Aciduria |
ASL
| c.556C > T (p.Arg186Trp) | Founder | Missense | |
c.1060C > T (p.Q354X) | Founder | Nonsense | ||||
Citrullinemia type 1 |
ASS1
| c.364-2A > G | Founder | Homozygous, intronic | ||
c.370G > A (p.Asp124Asn) | Founder | Homozygous, missense | ||||
Fatty acid oxidation defect | VLCAD |
ACADVL
| c.494 T > C(Phe165Ser) | Private | Homozygous, missense | |
VLCAD |
ACADVL
| c.65C > A (p.Ser22*) | Founder | Nonsense | ||
MCAD |
ACADM
| c.255 G > T(p.Gly119*);) | Private | Homozygous, nonsense | ||
c.938 T > G(p.Phe313Cys | Private | Homozygous, missense | ||||
Carnitine uptake defect |
SLC22A5
| c.1385G > A(p. Gly462Asp) | Private | Homozygous, missense | ||
Aminoacids transport defect | Cystinuria |
SLC3A1
| c.1711 T > A(p.Cys571Ser) | Founder | Homozygous, missense | |
c.1400 T > A (p.Met467Lys) | Private | |||||
SLC7A9
| c.1166 C > T(p.Thr389Met) | Private | Homozygous, missense | |||
Metal Transport Defect | Wilson disease |
ATP7B
| c.2230 T > C (p.Ser744Pro) | Founder | Homozygous, missense | |
Disorders od Haem biosynthesis | Acute Intermittent Poephyria |
HMBS
| c.760delC (p.Leu254X) | Founder | Nonsense | |
Cholesterol biosynthesis defect | CHILD syndrome |
NSDHL
| c.314C > T (p.Ala105Val) | Private | Homozygous, missense |
Disease category | Disease | Gene | Reported mutations | Novel mutations | Founder Vs. Private | Type of mutation | |
---|---|---|---|---|---|---|---|
LSD | Sphingolipidosis | Fabry |
GLA
| c. 782G > T (p.Gly261Val) | Founder | Homozygous, missense | |
Sandhoff disease |
HEXB
| c.1169 + 3_1169 + 10delAAGTTGTT (p.Gly65 AlafsX7) | Private | Deletion | |||
Niemann-Pick disease type B |
SMPD1
| c.1267 C > T (p.His423Tyr) | Founder | Homozygous, missense | |||
Niemann-Pick disease type C |
NPC1
| c.2130 + 1G > A; | Founder | Homozygous, intronic | |||
c.2443_2444delp.ser815Leufs*54 | Private | deletion | |||||
GM1 gangliosidosis |
GLB1
| c.950G > A(p. Trp317*) | Private | Homozygous, nonsense | |||
c.171C > G (p.Tyr57X) | Founder | Homozygous, missense | |||||
Metachromatic leukodystrophy |
ARSA
| c.1108-2A > G | Private | Homozygous, intronic | |||
Saposin B deficiency |
PSAP
| c.722G > C (p.Cys241Ser | Founder | Homozygous, missense | |||
Krabbe disease |
GALC
| c.396G > A(p.Trp132*) | Private | Homozygous, nonsense | |||
Mucopolysaccharidosis (MPS) | MPSI |
IDUA
| c.1868 T > C(p. Leu623Pro) | Private | Homozygous, missense | ||
MPSII |
IDS
| c.405A > C(p. Lys135Asn) | Private | Homozygous, missense | |||
MPSIIIA |
SGSH
| c.664-13C > G | Private | Homozygous, intronic | |||
c.535G > A (p.Asp179Asn) | Private | Homozygous, missense | |||||
MPS IVA |
GALNS
| c.120 + 1G > C (IVS1 + 1G > C) | Private | Homozygous, missense | |||
c.860C > T (p.Ser287Leu) | Private | Homozygous, missense | |||||
c.697G > A (p.Asp233Asn) | Private | Homozygous, missense | |||||
MPSVI |
ARSB
| c.753C > G (p.Tyr251*) | Founder | Homozygous, nonsense | |||
c.430A > G (p.His393ARG) | Founder | Homozygous, missense | |||||
c.1079 T > C (p. Leu360Pro) | Private | Homozygous, missense | |||||
Oligosaccharidosis | Mucolipidosis II |
GNPTAB
| c.3503_3504 delTC (p.Phex1172) | Private | Homozygous, deletion | ||
α-mannosidosis |
MAN2B1
| c.1340A > T (p.Asp447Val) | Private | Homozygous, missense | |||
Others | NCL type 6 |
CLN6
| c.794_796del(p.Ser265del) | Private | Homozygous, deletion | ||
c.794_796delCCT | Private | Homozygous, deletion | |||||
NCL type 8 |
CLN8
| Homozygous deletion encompassing exon2 | Private | Homozygous, deletion | |||
GSDII |
GAA
| c.1431delT(p. lle477fs) | Private | Homozygous, deletion | |||
c.1657C > T(p. Gln553*) | Private | Homozygous nonsense | |||||
Glycogen storage disease | GSDIII |
AGL
| c.4353G > T(p. Trp1451Cys); | Private | Homozygous, missense | ||
GSDIV |
GBE1
| c.998A > T (p.Glu 333 Val) | Private | Homozygous, missense | |||
GSD IX |
PHKG2
| c.130C > T (p.Arg44*) | Founder | Homozygous nonsense | |||
PHKB
| Deletion Exon 5 and 6 | Private | Homozygous, deletion | ||||
Mitochondrial disorders | Leigh disease |
MTATP6
| m.8993 T > G (p.Leu156Arg) | Private | Homoplasmic, missense | ||
COX15
| c.649C > T (p.Arg217Trp) | Private | Homozygous, missense | ||||
Pyruvate dehydrogenase deficiency |
PDHA1
| c.1256_1259dup (p.Trp421Serfs*6) | Private | Heterozygous Duplication | |||
PDHA1
| c.1132C > T (p.Arg378Cys) | Private | Hemizygous missense | ||||
Pyruvate Carboxylase Deficiency |
PC
| c.3116_3126del (p.Leu1039Glnfs*7) | Private | Deletion | |||
Mitochondrial DNA depletion syndrome 3 |
DGUOK
| c. 617G > A (p. R206k) | Private | Homozygous, missense | |||
Mitochondrial DNA depletion syndrome 5 |
SUCLA2
| c.362_363del (p.Ile121Serfs*38) | Private | Deletion | |||
Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 |
SCO2
| c.2 T > C(p.Met1?) | Private | Homozygous, missense | |||
3-Methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like |
SERAC1
| c.438del (p.Thr147Argfs*22) | Private | Deletion | |||
Primary CoenzymeQ10 deficiency type 5 |
COQ9
| chr16_57485062C > T (p.His62Arg) | Private | Homozygous, missense | |||
Peroxisomal disorders | Primary hyperoxaluria type 1 |
AGXT
| c.187G > C (p.Gly63Arg) | Founder | Homozygous, missense | ||
Zellweger syndrome |
PEX5
| c.1578 T > G (p.Asn526Lys) | Private | Homozygous, missense | |||
Rhizomelic chondrodysplasia punctata type 1 |
PEX7
| c.321_322delTA(p.Tyr107*) | Private | Homozygous, deletion | |||
Congenital disorder of glycosylation (CDG) | CGD 1 L |
ALG9
| c.1075G > A (p.E359K) | Private | Homozygous, missense |