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 for SO def � Little published data � Would not be able to sample healthy children
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
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
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
CSF Chromatograms reference Blood stained
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
Sulphite Oxidase Deficiency � 3 cases in 5 years � 1 isolated SO def � 2 molybdenum cofactor def
CSF amino acids: Sulphite oxidase deficiency sulfocysteine 19 µ mol/L
Glycine and serine � Glycine encephalopathy (NKH) − ↑ gly CSF, plasma, urine − Intractable seizures � 3 phosphoserine dehydrogenase deficiency − ↓ ser CSF − Intractable siezures, microcephaly
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
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
De Koning et al, Lancet 2004, 364; 2221
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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