CSF Amino Acids Reference Data and Interpretation Mick Henderson, - - PowerPoint PPT Presentation
CSF Amino Acids Reference Data and Interpretation Mick Henderson, Martin Smith and Carys Jones Biochemical Genetics Department of Clinical Biochemistry LTHTrust Background CSF amino acid critical for diagnosis of GE and 3PD def, helpful
Mick Henderson, Martin Smith and Carys Jones Biochemical Genetics Department of Clinical Biochemistry LTHTrust
CSF amino acid critical for diagnosis of GE and 3PD def, helpful for SO def Little published data Would not be able to sample healthy children
5 year period 94 CSF samples received, investigation
17 excluded − evidence of blood staining − diagnosis of aa disorder − age >12 months
77 infants aged <12 months
Amino acid Number of samples with detectable values Range (umol/L) Median umol/L 95 percentile (umol/L) Taurine 77 5 – 65 21 6 - 62 Aspartate 77 3 – 27 6 3 – 17 Threonine 77 9 – 187 44 12 – 178 Serine 77 24 – 105 52 25 – 105 Asparagine 75 ND – 38 9 3 – 37 Glutamate 77 2 – 97 12 2 – 50 Glutamine 77 226 – 1014 449 231 – 940 Proline 1 ND – 8 ND <1 Glycine 77 3 – 23 9 3 - 19 Alanine 77 12 – 62 33 15 – 60 Citrulline 38 ND – 9 3 0 – 9 Valine 77 5 – 49 19 7 – 48 Cystine 4 ND – 4 ND <1 Methionine 66 ND – 36 6 2 – 30 Isoleucine 76 ND – 20 6 1 – 16 Leucine 77 5 – 38 15 5 – 35 Tyrosine 77 4 – 80 18 5 – 54 Phenylalanine 77 4 – 41 13 6 – 40 Ornithine 76 ND - 31 6 2 – 21 Lysine 77 6 – 51 20 7 – 42 Histidine 77 7 – 45 18 7 – 38 Tryptophan ND ND <1 Arginine 72 ND - 41 19 7 – 40 s-sulphocysteine ND ND <1
Data distributions for CSF glycine and serine concentrations (n=77)
Box; 25th – 75th percentiles, lines; 2.5th – 97.5th percentiles)
1 2.5 5 7.5 10 12.5 15 17.5 20 22.5 25
Median [glycine] = 9.0µmol/L Range = 3-23 µmol/L 2.5th percentile = 3.0 µmol/L 97.5th percentile = 19.2 µmol/L [glycine] µmol/L
Glycine Serine
1 20 30 40 50 60 70 80 90 100 110
[serine] µmol/L Median [serine] = 52.0µmol/L Range = 24-105 µmol/L 2.5th percentile = 25.0 µmol/L 97.5th percentile = 105.0 µmol/L
reference Blood stained
Amino acid concentrations; 95th Centile upper limits
100 200 300 400 500 600 700 800 900 1000 T a u r i n e A s p a r t a t e T h r e
i n e S e r i n e A s p a r a g i n e G l u t a m a t e G l u t a m i n e P r
i n e G l y c i n e A l a n i n e C i t r u l l i n e V a l i n e C y s t i n e M e t h i
i n e I s
e u c i n e L e u c i n e T y r
i n e P h e n y l a l a n i n e O r n i t h i n e L y s i n e H i s t i d i n e T r y p t
h a n A r g i n i n e s
u l p h
y s t e i n e umol/L
CSF Plasma
3 cases in 5 years 1 isolated SO def 2 molybdenum cofactor def
sulfocysteine 19 µmol/L
Glycine encephalopathy (NKH) − ↑ gly CSF, plasma, urine − Intractable seizures 3 phosphoserine dehydrogenase deficiency − ↓ ser CSF − Intractable siezures, microcephaly
Case CSF plasma ratio Ref 3 - 19 220 - 527 < 0.08 1 241 904 0.27 2 206 1473 0.14 3 189 1401 0.13 4 134 610 022 5 104 227 0.46 6 135 732 0.18
Successful prenatal treatment of 3PGD def, De
Koning et al Lancet Dec 2004 (364 p2221)
2 previous sibs − Serine suppl diet controlled seizures − Severe microcephaly Maternal serine supplementation from 26 w
De Koning et al, Lancet 2004, 364; 2221
Healthy baby girl born at term Wt and ht on 40th centile, head 30th Cord plasma ser 52 umol/L (124 – 180) Serine supplements given from birth Child 4 yrs at time of report, growth neurological status and psychmotor dev normal