Table 3.
Mutations for small molecule IEMs
| 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 |
PKU phenylketonuria, MSUD maple syrup urine disease, VLCAD very long-chain acyl-CoA dehydrogenase, MCAD medium-chain acyl-CoA dehydrogenase