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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