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Table 1 Patient sample, diagnostic criteria and treatment modalities

From: Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

Disorder N Group 1
NBS
Group 2
symptomatic
Group 3
high risk
Treatment Confirmation of diagnosis
Minimal criteria to accept diagnosis as confirmed
      Yes No Un-known  
Amino acid disorders/ Urea cycle disorders
PKUa,f 85 84   1b 79 0 6 Blood phenylalanine ≥ 600 μmol/L, normal urinary pterins and DBS dihydropteridine reductase activity
MHPa,f 88 88    2 61 25 First and control phenylalanine levels < 600 μmol/L, phenylalanine/tyrosine < 3, normal urinary pterins and DBS dihydropteridine reductase activity
PTPSDe 1 1    1    Characteristic pterin profile in urine
MSUDa, e 7 4 1 2 7    Elevated branched-chain amino acids including alloisoleucine
TYR Ie 2 2    2    Elevated succinylacetone in urine
TYR IIIf 1 1    1    Tyrosine persistently > 500 μM, succinylacetone in urine normal, no clinical indication for tyrosinaemia type II or liver dysfunction
Homocystinuriaf 0        Characteristic profile of homocysteine, methionine, cysteine in plasma
NKHc,f 1 1     1   Elevated glycine in plasma and CSF and pathological ratio plasma/CSF glycine
CIT I classice 4 1 3   3   1 Characteristic amino acid profile in plasma and ammonia in blood
CIT I mildf 6 6    1 5   Characteristic amino acid profile in plasma and ammonia in blood, molecular genetic analysis
ASLDe 1    1 1    Characteristic amino acid profile in plasma and urine
Arginase deficiencyf 0        Enzyme deficiency in erythrocytes
Fatty acid oxidation disorders     
CPT IDa,e 1 1    1    Enzyme deficiency in fibroblasts
CPT IIDa,e 1 1    1    Enzyme deficiency in fibroblasts
CACTDa,e 0        Enzyme deficiency in fibroblasts
CTDe 3 3    3    Pathological tubular carnitine reabsorption, fibroblast transport studies
MCADDa,e 81 77 2 2 70 1 10 Characteristic acylcarnitine profile in plasma/DBS and/or hexanoylglycine in urine and/or informative genotype
LCHADD/
mTFPa,c,e
6 5   1 5   1 Characteristic acylcarnitine profile in plasma/DBS and/or informative genotype and/or enzyme activity
VLCADDa,e 6 6    6    Characteristic acylcarnitine profile in plasma/DBS and/or enzyme activity in lymphocytes or fibroblasts and/or informative genotype
SCADDf 9 9     3 6 Characteristic acylcarnitine profile in plasma/DBS and ethylmalonic acid in urine and enzyme activity
MADDe 3 3    2   1 Characteristic profiles of acylcarnitines in plasma and organic acids in urine
Organic acid disorders       
GA Ia,e 6 6    6    Characteristic urinary organic acid profile, informative genotype
IVA classica,e 5 4 1   5    Characteristic urinary organic acid profile
IVA milda,f 10 9   1 10    Characteristic urinary organic acid profile, informative genotype
MBDf 0        Characteristic urinary organic acid profile
MMA/Cble 4 3 1   4    Characteristic urinary organic acid profile +/- abnormal concentrations of plasma homocysteine and methionine (complementation studies in fibroblasts in all patients)
PAe 4 3 1   4    Characteristic urinary organic acid profile
3-MCCDf 8 8    5 2 1 Characteristic urinary organic acid profile
MHBDe 0        Characteristic urinary organic acid profile, informative genotype
MGAe 0        Characteristic urinary organic acid profile, informative genotype
HCSDe 0        Characteristic urinary organic acid profile, enzyme deficiency
BIODa,e 9 9    7   2 Enzyme deficiency in DBS and/or serum
KTDe 0        Characteristic profiles of acylcarnitines in plasma and organic acids in urine
HMG-CoA LDe 1 1    1    Characteristic profiles of acylcarnitines in plasma and organic acids in urine
Other disorders         
Galactosaemiaa,e 14 9 2 3 12   2 Enzyme deficiency and elevated galactose-1-phosphate in DBS and erythrocytes
Others conditions       
Maternal
3-MCCDf
6 6     6   Characteristic acylcarnitine profile in plasma/DBS of mother and clearing of the pathological profile in the newborn
Not confirmedd 4 4     3 1  
Total 377 355 11 11 239 82 56  
  1. a Legal screening panel in Germany from April 1st 2005 onward
  2. b Diagnosed by prenatal diagnosis
  3. c Deceased: One child with mTFP at 6 months, one child with NKH in the neonatal period
  4. d Screening diagnoses: 1 CTD lost to follow up; 1 MMA lost to follow up; 1 MCADD, gestational age = 26 wks., deceased in neonatal period; 1 TYR I, gestational age = 25 wks., deceased in neonatal period
  5. e Disorder with risk of metabolic decompensation
  6. f Disorder without risk of metabolic decompensation
  7. Abbreviations: ASLD = Argininosuccinate lyase deficiency; BIOD = Biotinidase deficiency; CACTD = Carnitine acylcarnitine translocase deficiency; CIT I = Citrullinaemia type I; CPT ID = Carnitine palmitoyltransferase I deficiency; CPT IID = Carnitine palmitoyltransferase II deficiency; CTD = Carnitine transporter deficiency; GA I = Glutaric aciduria type I; HCSD = Holocarboxylase synthetase deficiency; HMG-CoA LD = 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency; IVA = Isovaleric aciduria; KTD = β-Ketothiolase deficiency; LCHADD = Long-chain 3-hydroxy-acyl-CoA dehydrogenase deficiency; mTFP = mitochondrial tri-functional protein deficiency; MADD = Multiple acyl-CoA dehydrogenase deficiency; MCADD = Medium-chain acyl-CoA dehydrogenase deficiency; MBD = 2-Methylbutyryl-CoA dehydrogenase deficiency; 3-MCCD = 3-Methylcrotonyl-CoA carboxylase deficiency; MGA = 3-Methylglutaconic aciduria; MHBD = 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency; MHP = Mild hyperphenylalaninaemia; MMA/Cbl = Methylmalonic acidurias (all kinds); MSUD = Maple syrup urine disease; NKH = Non-ketotic hyperglycinaemia; PA = Propionic aciduria; PKU = Phenylketonuria; PTPSD = 6-Pyruvoyltetrahydropterin synthase deficiency; SCADD = Short-chain acyl-CoA dehydrogenase deficiency; TYR I/III = Tyrosinaemia type I/III; VLCADD = Very long-chain acyl-CoA dehydrogenase deficiency