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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


  1. CSF Amino Acids Reference Data and Interpretation Mick Henderson, Martin Smith and Carys Jones Biochemical Genetics Department of Clinical Biochemistry LTHTrust

  2. Background � 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

  3. Data Review � 5 year period � 94 CSF samples received, investigation of infants with fits/seizures � 17 excluded − evidence of blood staining − diagnosis of aa disorder − age >12 months

  4. CSF amino acid concentrations 77 infants aged <12 months Amino acid Number of samples Range Median 95 with detectable (umol/L) umol/L percentile values (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 75 ND – 38 9 3 – 37 Asparagine 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 76 ND – 20 6 1 – 16 Isoleucine 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 0 ND ND <1 Tryptophan Arginine 72 ND - 41 19 7 – 40 s-sulphocysteine 0 ND ND <1

  5. Data distributions for CSF glycine and serine concentrations (n=77) Box; 25 th – 75 th percentiles, lines; 2.5 th – 97.5 th percentiles) Glycine 1 Median [glycine] = 9.0 µ mol/L Range = 3-23 µ mol/L 2.5 th percentile = 3.0 µ mol/L 97.5 th percentile = 19.2 µ mol/L 0 2.5 5 7.5 10 12.5 15 17.5 20 22.5 25 [glycine] µ mol/L Serine 1 Median [serine] = 52.0 µ mol/L Range = 24-105 µ mol/L 2.5 th percentile = 25.0 µ mol/L 97.5 th percentile = 105.0 µ mol/L 0 20 30 40 50 60 70 80 90 100 110 [serine] µ mol/L

  6. CSF Chromatograms reference Blood stained

  7. Amino acid concentrations; 95th Centile upper limits 1000 CSF 900 Plasma 800 700 600 umol/L 500 400 300 200 100 0 e e e e e e e e e e e e e e e n e e e e e e e e t n n n n n n n n n n n n n n n n a n a n n n t n i i i i i i i i a i i i i l i i i i i h i r i m l c n t n n h i d n r g m l l c c s s n i u o a t e u s p e o y a o u o a t i r a a u y t i a a r V y i g a S l r i l s o t e P l e r n s r t G t e a L T t A C h y p u i r i t r r a u C l H y t o L l p A T y O s h l e c p l G y A G s n T M o s r I e A T h h p P l u s - s

  8. Sulphite Oxidase Deficiency � 3 cases in 5 years � 1 isolated SO def � 2 molybdenum cofactor def

  9. CSF amino acids: Sulphite oxidase deficiency sulfocysteine 19 µ mol/L

  10. Glycine and serine � Glycine encephalopathy (NKH) − ↑ gly CSF, plasma, urine − Intractable seizures � 3 phosphoserine dehydrogenase deficiency − ↓ ser CSF − Intractable siezures, microcephaly

  11. Experience with GE 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

  12. Ante natal Rx 3PGD Deficiency � 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

  13. De Koning et al, Lancet 2004, 364; 2221

  14. Prenatal serine therapy: outcome � Healthy baby girl born at term � Wt and ht on 40 th centile, head 30 th � 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

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