Metabolic Screening Laboratory Dr J.D. Shoemaker MD PhD Dept of Biochemistry 1402 S Grand Ave St Louis, MO (314)
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1 Dr J.D. Shoemaker MD PhD Dept of Biochemistry 1402 S Grand Ave St Louis, MO (314) Urine Organic Compounds Date: 4/16/09 Time: 9:27 AM To: Re: SSM Cardinal Glennon Children's Medical Center 1425 S Grand Ave St. Louis, MO Name: Hawkinsinuria Clinic / Req #: Date Collected: Results: This sample contained 1.72 um creatinine /ml and other peaks considered to be: Within Normal Limits X Abnormal Unidentified, Mass Spectra Available on Request Tentatively Identified X Positively Identified Excretion of hawkinsin and 4-hydroxycyclohexylacetate indicates hawkinsinuria in this child with hemolytic anemia. Massive excretion of pyroglutamic acid is found. Pyroglutamic acidemia accounts for acidosis in this child. James D. Shoemaker MD Director
2 Quantified Target Panel Metabolic Screening Lab Dr J.D. Shoemaker MD PhD Urine Organic Compounds Patient Name Hawkinsinuria Data File OCM104 10/17/08 mm/m mm/m mm/m Organic Acids Creatinine Neurotransmitters Creatinine Acyl Glycines Creatinine Lactic GABA 1.36 Propionyl Glycine 0.00 Pyruvic Homovanillic Butyryl Glycine 0.00 Glycolic Normetanephrine 0.32 Hexanoyl Glycine 0.80 Hexanoic Vanillylmandelic 5.70 Phenylpropionyl Glycine Hydroxybutyric 8.27 Metanephrine 2.02 Suberyl Glycine Hydroxybutyric HIAA Isobutyryl Glycine Hydroxybutyric MHPG 3.36 Isovaleryl Glycine 0.00 Acetoacetic 1.23 Ethanolamine 7.60 Tiglyl Glycine Hydroxycaproic 4.13 Phosphoethanolamine 0.79 Beta-Met Crotonyl Glycine 0.08 b-lactate Octanoic Nutritionals Carbohydrates Succinic Methylsuccinic 3.73 Kynurenine 6.08 Arabinitol Glutaric Formiminoglutamic Dulcitol a-ketoglutarate Pyridoxic 2.95 Erythritol Fumaric Pantothenic Inositol Malic Xanthurenic 0.09 Mannitol Adipic Kynurenic Ribitol Suberic Quinolinic 3.55 Sorbitol Sebacic Orotic Threitol Glyceric d-aminolevulinic Xylitol Methylmalonic Methylhistidine Galactonic Acid Ethylmalonic Methylhistidine Glucaric Acid Homogentisic 6.27 Niacinamide 2.11 Gluconic Acid Phenylacetic Pseudouridine Glucuronic Acid Phenyllactic Deoxytetronic Arabinose Phenylpyruvic Xanthine Fructose p-hydroxyphenylacetic Hypoxanthine Fucose p-hydroxyphenyllactic Urocanic 2.84 Galactose p-hydroxyphenylpyruvic Ascorbic Glucose Succinylacetone Glycerol Isomaltose Hydroxyisovaleric Glycerol-3-Phosphate Lactose Phosphate Ribose Citric Sucrose Isocitric Xylose Hippuric Levoglucosan Uric Pyroglutamic Amino Acids Uracil 8.03 Thymine 0.07 Glycine Lysine Tartaric Alanine Histidine Oxalic Sarcosine Threonine Methylguanine B-Alanine 5.58 Homoserine Oxoadipic B-Aminoisobutyric Phosphoserine 4.52 Serine Methionine 3.95 Miscellaneous Proline Cysteine Hydroxyproline 3.80 Homocysteine Aminoadipic Aspartic Cystathionine Hydroxyadipic 1.70 Asparagine Cystine Hydroxyglutaric 5.33 N-Acetyl Aspartic 5.63 Homocystine Hydroxysebacic N-Acetyl Cysteine Phenylalanine Methylcitric N-Acetyl Tyrosine Tyrosine Hydroxyglutaric Ornithine 1.83 Tryptophan Hydroxy-3-methylglutaric Glutamic Hydroxyisobutyric Glutamine Hydroxysebacic Pipecolic Methylglutaconic Leucine Methylglutaric 5.01 Ketoleucine Hydroxycyclohexylacetic Valine Benzoic Ketovaline 1.75 cis-aconitic 2.61 Isoleucine Sialic Ketoisoleucine 1.26 This Sample Contained 0.86 umoles Creatinine/Sample
3 Data File : :\OCMD\Completed\OCM104.D Acq On : 17 Oct :46 Instrument ID : US Dr James Shoemaker MD PhD Pk# RT Area% Urine Constituents - Best fit from library Ref# Qual ,4-Cyclohexadiene, 6-isopropenyl-2,4-dimethyl-1, Silanamine, N,N'-methanetetraylbis[1,1,1-trimethyl ,8-Dioxa-2,9-disiladec-5-ene, 2,2,9,9-tetramethyl Propene, 3-propoxy LACTIC ACID DI-TMS Hexenoic acid, 4-methyl-6-(fluorodimethylsilyl) Decanoic acid, tert-butyldimethylsilyl ester N,N-Diethyl-1,1,1-trimethylsilylamine LACTIC ACID DI-TMS LACTIC ACID DI-TMS C3 Lactic Acid TMS SARCOSINE DI-TMS GLYCINE DI-TMS ALPHA HYDROXYBUTYRIC ACID DI-TMS ALANINE DI-TMS Quinoline, 2-(1-methylethyl) BETA-LACTATE DI-TMS HYDROXY BUTYRIC ACID DI-TMS HYDROXY PENTANOIC ACID DI-TMS BETA AMINO BUTYRIC ACID DI-TMS ,1,1,3,5,5,7,7,7-Nonamethyl-3-(trimethylsiloxy)tet METHYLSUCCINIC ACID DI-TMS METHYL 2-OXO BUTYRATE DI-TMS (ketovaline), HYDROXY-ISOVALERIC, DI-TMS METHYLMALONIC ACID DI-TMS VALINE DI-TMS Succinic Acid DI-TMS METHYL ALANINE DI-TMS Dipropylacetic acid, trimethylsilyl ester Urea, N,N'-bis(trimethylsilyl) Glycerol-3-Phosphate TMS PROLINE DI-TMS HYDROXY BUTYRIC ACID DI-TMS ,8-Dioxa-2,9-disiladec-5-ene, 2,2,9,9-tetramethyl Citric Acid TMS HYDROXY BUTYRIC ACID DI-TMS GLYCERIC ACID TRI-TMS METHYL 3-OXOBUTYRATE DI-TMS DE-O TETRONIC TMS3 THREO SERINE TRI-TMS THREONINE N,O,O-TRI-TMS SILANE, 2-ETHOXYETHOXY TRIMETHYL ,4 DIHYDROXY BUTYRIC ACID TRI-TMS hydroxyadipic acid tri-tms, BUTANEDIOIC ACID, TMS-OXY-, BIS-TMS ESTER BUTANEDIOIC ACID, TMS-OXY-, BIS-TMS ESTER PYROGLUTAMIC ACID DI-TMS CREATININE ENOL TRI-TMS (R*,S*)-2,3-Dihydroxybutanoic acid, tris(trimethyls Keto-l-gluconic acid, penta(o-trimethylsilyl)-, HYDROXYGLUTARIC TRI-TMS, HEXENEDIOIC ACID DI-TMS, E Trimethylsilyloxycyclohexylacetate, trimethylsily GLUTAMIC ACID TRI-TMS PARA-HYDROXYPHENYLACETIC ACID DI-TMS Xylonic acid, 2,3,5-tris-O-(trimethylsilyl)-,.gamm hydroxyadipic acid tri-tms, TARTARIC ACID TETRA-TMS, ARABINOSE TETRA-TMS HYDROXYDODECANEDIOIC ACID-tri-TMS, OCMD.M Fri Jan 22 12:14: Page: 1
4 Data File : D:\OCMD\Completed\OCM104.D Acq On : 17 Oct :46 Instrument ID : US Dr James Shoemaker MD PhD Bis(trimethylsilyl)bromosuccinate hydroxyglutarate, Suberic Acid di-tms, hydroxyglutarate, Levoglucosan, tris(trimethylsilyl)-, GALACTOSE PENTA-TMS XYLITOL PENTA-TMS myo-inositol hexa-tms, n-octanoic acid, pentamethyldisilanyl ester (2,2-Dimethyl-propionyl)-tris(trimethylsilyl)silane ,3-Dihydroxyacetone dimer GALACTONIC ACID HEXA-TMS NONANEDIOIC ACID DI-TMS AZELAIC D-XYLOPYRANOSE TETRA-TMS Galactonic acid, 2,3,4,5,6-pentakis-O-(trimethylsil ALPHA.-D-GALACTOSIDE, METHYL TETRAKIS-O-TMS Ethylglucuronide per-tms, ALPHA.-D-GLUCOPYRANURONIC ACID, 1,2,3,4-TETRAKIS-O BETA.-D-GALACTOFURANOSE, 1,2,3,5,6-PENTAKIS-O- TMS Chloro-4-[p-[1-dimethylaminocyclohexylmethyl]anil d6 Sebacic Acid TMS BETA.-D-GALACTOFURANOSIDE, ETHYL 2,3,5,6-TETRAKIS P-HYDROXYPHENYL LACTIC ACID TRI-TMS D-MANNOPYRANOSE PENTA-TMS GALACTOSE PENTA-TMS Histidine per-tms, D-RIBOFURANOSE TETRA-TMS N,O-Bis(trimethylsilyl)-L-phenylalanine MANNITOL HEXA-TMS Glucose oxime hexakis(trimethylsilyl) Galactonic acid, 2,3,4,5,6-pentakis-O-(trimethylsil ALPHA.-D-GALACTOPYRANOSE, 1,2,3,4,6-PENTAKIS-O- TM GALACTOSE PENTA-TMS GALACTOSE PENTA-TMS Hexanedioic acid, 3-oxo-, tris(trimethylsilyl) deri PALMITIC ACID TMS SACCHARIC TMS ALPHA.-L-GALACTOFURANOSE, 6-DEOXY-1,2,3,5-TETRAKIS ALLO-INOSITOL HEXA-TMS hydroxysebacic acid tri-tms, Galactonic acid, 2,3,5,6-tetrakis-O-(trimethylsilyl GLYCERIC ACID TRI-TMS d-glucitol, 2-(acetylamino)-2-deoxy-1,3,4,5,6-penta Keto-l-gluconic acid, penta(o-trimethylsilyl)-, d6 Inositol TMS , YB PENTANEDIOIC ACID, 2,4-BIS TMS-OXY -, BIS-TMS ESTER D-XYLOPYRANOSE TETRA-TMS Estra-1,3,5(10)-trien-17-one, 2,3-bis[(trimethylsil methylguanine di-tms, LINOLEIC ACID TMS Hydroxy Indole Acetic Acid TRI-TMS I.S.:5-deutero-tryptophan per-tms, ALTRONIC ACID, 2,3,5,6-TETRAKIS-O-TMS-, LACTONE Pregnan-20-one, 3,11,21-tris[(trimethylsilyl)oxy]-, Gulonic acid, 2,3,5,6-tetrakis-O-(trimethylsilyl)-, Gulonic acid, 2,3,5,6-tetrakis-O-(trimethylsilyl)-, D-Fructose, 1,3,4,5,6-pentakis-O-(trimethylsilyl) ALPHA.-D-GALACTOPYRANOSE, 1,2,3,4,6-PENTAKIS-O- TM (N-Methyl-N-nitroamino)-4-[2,2,3,3,3-pentafluoro ARABINO-HEXARIC ACID, 2-DEOXY-3,4,5-TRIS-O- TMS-, B GALACTOSE PENTA-TMS BETA.-D-GALACTOFURANOSE, 1,2,3,5,6-PENTAKIS-O- TMS Sebacic acid, bis(trimethylsilyl) ester D-RIBOSE TETRA-TMS OCMD.M Fri Jan 22 12:14: Page: 2
5 Data File : D:\OCMD\Completed\OCM104.D Acq On : 17 Oct :46 Instrument ID : US Dr James Shoemaker MD PhD Piperazine, 2,5-diketo-, bis(trimethylsilyl) Propene-1,2,3-tricarboxylic acid, tris(trimethyls Chloral hydrate glucuronide per-tms, HAWKINSIN PENTA-TMS, HAWKINSIN PENTA-TMS, FUMARIC ACID DI-TMS, ,4,6 1H,3H,5H-PYRIMIDINETRIONE, 5-3-CHLORO-2- TMS Palmitate monoglyceride di-tms, D-XYLOPYRANOSE TETRA-TMS D-RIBOSE TETRA-TMS BETA.-D-GALACTOFURANOSIDE, ETHYL 2,3,5,6-TETRAKIS GALACTOSE PENTA-TMS D-XYLOPYRANOSE TETRA-TMS N2-(4-Chlorophenyl)-2,2-diphenyl-N1,N1-dipropylacet Octadecanoic acid, 2,3-bis[(trimethylsilyl)oxy]prop ALPHA.-D-GALACTOPYRANOSE, 1,2,3,4,6-PENTAKIS-O- TM Xanthumin Fluoro-3,4-dihydro-3-[4-[trifluoromethyl]phenyl] H-Indole-2,3-dione, 1-(tert-butyldimethylsilyl) Zirconium, bis(.eta.5-2,4-cyclopentadien-1-yl)bis( beta.,5-Bis(trimethylsiloxy)-5.alpha.-cholestane d3 Serine TMS OCMD.M Fri Jan 22 12:14: Page: 3
6 Metabolic Screeing Laboratory File : D:\OCMD\Completed\OCM104 Acquired : 17 Oct :46 Abundance TIC: OCM104.D\data.ms 1.4e e+07 1e Time--> Abundance TIC: OCM104.D\data.ms 1.4e e+07 1e Time-->
7 Table I. Inborn errors diagnosed in 13,242 patients using the Urease method Prior to State Newborn Screening by Tandem Mass Spectrometry Diagnoses in Red would probably not have been made by liquid or solid phase extraction organic acid analysis, or tandem mass spectrometry. Of 14,919 Samples, from 13,242 patients 1691 Abnormal 11% 164 confirmed Inborn Errors + 20 MADD or cystinuria 184 Total 1.38% 48 involved non-acidic metabolites 28 involved orotate or hexanoylglycine 35-70% increase due to urease method Of 184 Inborn Errors: 14 Urea cycle 2 HMG 18 MCAD 3 SCAD 14 LCHAD 2 Hyperoxaluria 10 MMA 4 Renal Fanconi 7 MSUD 3 Molybdenum Cofactor Def 5 Propionic 9 Galactosemia 2 Iminoaciduria 12 Glutaric I 4 Cystinuria 5 Biotinidase 3 Adrenoleukodystrophy 4 Glutaric II 2 Pyruvate Dehydrogenase, 2 Glyceroluria 2 Hereditary Fructose Intolerance 2 FIGLU uria, 2 Homocystinuria 2 Glycerate kinase def 2 Hartnup s 2 Hypophosphatasia 3 3-methylglutaconic 3 3-methylglutaconic 3 Adrenoleukodystrophy 3 Cystathioninase def 4 beta-methylcrotonyl CoA carboxylase 4 Sialuria 6 Pyroglutamic Single cases: PKU Alkaptonuria Fumaric 2-Hydroxyglutaric Proline Oxidase, Succinic Semi-aldehyde dehydrogenase Deficiency Canavan s Disease Renal Glycosuria, Pyruvate dehydrogenase def Hawkinsinuria Hepato-Renal Tyrosinemia
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