適用罕見疾病防治及藥物法之藥物年報第三期

Transcription

1 Pompe 8 10 (Homocystinuria) A-1 A-6 A A-24 A-29 A-33 ICD-9-CM A-40 A-45 1

2 2

3 3

4 ,350 1,098 4

5

6 (1) (2) (3) (4) (1) (2) (3)

7 7

8 8 Pompe lysosome Glycogen Acid Maltase -glucosidase X PR

9 9 3 2 X

10 Inborn error of metabolism, IEM --- Organic acidemias Aminoacidopathies Fatty metabolic disorders Lysosomal storage disease, LSD Metabolic disorders of porphyrins Metabolic disorders of purines and pyrimidines Metabolic disorders of metals Transport disorders 酶 Enzyme replacement therapy, ERT 10

11 8,000 Mannose-6-phosphate-receptor-mediated pathway ERT ERT Gaucher disease type 1 CerezymeRecombinant human acid -glucosidase Fabry disease Fabrazyme ReplagalRecombinant human -galactosidase --- / Mucopolysaccharidosis type I, Hurler/Schiei syndrome AldurazymeRecombinant human -L-Iduronidase --- Glycogen storage disease type II, Pompe disease Acid -glucosidase / Phase 1/2 Phase 3 Arylsulphatase Iduronate-2-sulphatase ERT ERT LSD Pharmacological chaperones Enzyme enhancement therapy, EET 11

12 酶 X 酶 Y 酶 Z A B C D 酶 X A A A 酶 酶 D 酶 Y B B D B B 酶 Y D D 12

13 (Homocystinuria) ( 46 mmhg) (Methionine) 772µmol/L (Homocystine) 47.09µM (Silver nitroprusside test Cyanide nitroprusside test) (0.804 ± 0.01 g/cm 2 ) 40 (Hominex-2) (Folic acid)betaine B6Aspirin Persantin Methionine Homocystine undetectable 0.3%-5% (methionine, MET) methionine-s-adenosyltransferase, MAT S-adenosylmethionine (homocysteine) (homocysteine) (MET) (cysteine) (homocystine) CBS { (cystathionine-β-synthase, CBS)} (cysteine) methylmalonic aciduria (homocystinuria) 13

14 1. Methylenetetrahydrofolate reductase 2. 5-methyltetrahydrofolate-homocysteine methyltransferase 3. CBS CBS CBS 14

15 (CBS ) (newborn screen) 1mg/dL blood CBS : 骺 15

16 () B6 B6 CBS CBS B6 CBS CBS 13% B6 B6 25mg 100mg B6 1gm B6 B6 () B6 B6 1000mg/day (Hominex-2) (L-cysteine) (betaine) Betaine (methylation) 16

17 (folic acid) B12 (folate) B12 () µmol/l µmol/l () (methionine) (L-Cystine) (Betaine) (Folate) (kcal/day) (g/day) (mg/kg/day) (mg/kg/day) (g/day) (mg/day) /kg 3-3.5/kg 35 (20-50) /kg 2.5-3/kg 28 (15-40) (10-30) 150 ( ) (10-20) 150 ( ) (10-20) 150 ( ) (10-20) 75 (50-60) : nutrition support of Inborn Errors of Metabolism in Handbood of Pediatirc Nutrition. 2 nd ed p255 Aspirin Persantin Vit B6 17

18 Dwarf midgets 100 ( ) 75-90% 0% 50% 25% 25% 1994 John Wasmuth 4 3 (fibroblast growth factor receptor-3 gene, FGFR3 ) G1138A (G380Rglycine to arginine)? ( ) 18

19 O ( ) ( ) (2-3 ) ( 1998 / 193 J Med Genet 1998; 35: ) (18.6%) 11% 2 8% 16% 80% 40% 16% 3%? 90-98%? ? 19

20 3-4 ( ) 2-3 (5-6 )? ; 3% 5% < 5% ( restrictive pulmonary disease ) ( reactive airway disease ( arm span ) (occipital frontal circumferenceocf )

21 ? ( ) LPA (Little People of America)HGF (Human Growth Foundation) - TEL: (02) National Library of Medicine Genetics Home Reference Achondroplasia NCBI Genes and Disease Webpage Achondroplasia Human Growth Foundation 21

22 Phone: Fax: Little People of America (LPA) Phone: 888-LPA-2001 ( ); Fax: MAGIC Foundation for Children's Growth Phone: Fax:

23 (Huntington s chorea) Westphal variant 2. (1) saccadic eye movements clumsiness bradykinesia dystonia 17 23

24 myoclonus seizures (2) (irritability) major depressive disorder mania apathy (3) subcortical dementia caudate nucleus putamen corpus striatum, 20% huntingtin exon CAG huntingtin Huntingtin allele CAG Anticipation 24

25 60 huntingtin CAG 苷 Neurology 347 酶 coenzynme Q10 NMDA remacemide 30 coenzyme Q10 caspase inhibitor minocycline, creatine, lithium, ethyl eicosapentaenoic acid, cystamine, bile acids,inhibitors of transglutaminase typical neuroleptic Amantadine tetrabenazine olanzapine SSRI carbamazepine valproic acid 25

26 (Kabuki syndrome) 1981 (Kuroki) (Niikawa) Niikawa-Kuroki syndrome - Kabuki make-up syndrome () (long palpebral fissures)(100%) (large protruding ears) (ectropion, eversion of the lateral one-third of the lower palpebrae)(98%) (arched eyebrows) (88%) (depressed nasal tip)(79%) (85%) (micrognathia)() ( )(brachydactyly) (clinodactyly)(89%) (scoliosis)(49%) () (digital ulnar loops) c d (digital triradius c, d) bc cd (interdigital triradius bc, cd) (hypothenar loops) (fetal fingertip pads) (75%)() IQ () ( )(73%) 腭 (high-arched palate) 腭 (cleft palate) (cleft lip) (lower pits) ( ) (hypotonia) (epilepsy) (feeding problems) (microcephaly 30-50%) (33%) (strabismus) ( ) 1/32,000 ( () () 26

27 10-12 (X Y) Y X Y ( ) - (variable expressivity) : ( ) 50% (germline cells) (mosaic mutations) IQ 80 27

28 (collagen) (production and resorption) (remodeling) (osteoblast) (procollagen type I) osteonectinosteocalcin proteoglycanalkaline phosphate (osteoclast) (cross-link) (osteogenesis imperfecta) (brittle bone disease) (procollagen) Gly-X-Y COL1A1 17q21.3-q22 COL1A2 7q

29 I Ia Ib II III IV IVa IVb X Dual-energy x-ray absorptiometry(dexa) X Pamidronate 30mg/m 2 X gms/cm gms/cm2z score

30 (rod fixation) pamidronate Brumsen (1997)Bembi B (1997) Glorieux FH (1998) pamidronate pamidronate Pamidronate 30mg/ m 2 (biphosphate) 30

31 Levocarnitine Thalidomide citrulline, oral solution, 1 g/10 ml citrulline Risedronate Bosentan, 62.5 and 125 mg tablet Laronidase, 100 units/ml solution for infusion Tretinoin, soft gelatin capsules 10 mg Tetrahydrobiopterin (BH4) 50 mg/tab Diazoxide persistent hyperinsulinemic hypoglycemia of infancy (PHHI)

32 ( ) 01 Urea cycle disorders Citrullinemia Amino acid metabolic disorders ( Aminoacidopathies) A Homocystinuria Hypermethioninemia Cystinosis Nonketotic hyperglycinemia Phenylketonuria Tetrahydrobiopterin deficiency Hereditary tyrosinemia Maple syrup urine disease Hereditary coproporphyria Multiple sclerosis Gaucher's disease Wilson's disease Nesidioblastosis Amyotrophic lateral sclerosis (ALS) Organic acidemias Isovaleric acidemia Glutaric aciduria type I, II Propionic acidemia Methylmalonic acidemia Hydroxy-3-methyl-glutaric acidemia Galactosemia Fatty acid oxidation defect Carnitine deficiency syndrome, primary

33 12 Mitochondrial defect Kearns-Sayre syndrome Kearns-Sayre Leigh disease Leigh MELAS MELAS Mitochondrial Neurogastrointestinal Encephalopathy Syndrome MNGIE Aarskog-Scott syndrome Aarskog-Scott Achondroplasia Angelman syndrome Angelman Ataxia telangiectasia Cockayne syndrome Cockayne Duchenne muscular dystrophy Glycogen storage disease GM1/GM2 gangliosidosis GM1/GM Hereditary epidermolysis bullosa Huntington disease Huntington's chorea) Hutchinson Gilford progeria syndrome 24 Ichthyosis, lamellar recessive Kenny-Caffey syndrome Kenny-Caffey Lesch-Nyhan syndrome Lesch-Nyhan Lowe syndrome Lowe Mucopolysaccharidoses Osteogenesis imperfecta Pseudohypoparathyroidism Rett syndrome Spinal muscular atrophy Spinocerebellar ataxia Sulfite oxidase deficiency 酶 Thalassemia major Tuberous sclerosis Waardenburg syndrome A-2

34 38 X-linked hypophosphatemic rickets Zellweger syndrome Zellweger Progressive intrahepatic cholestasis PFIC Inborn errors of bile acid synthesis Primary Paget disease Urea cycle disorders Nitroacetylglutamate synthetase deficiency,nag synthetase deficiency Ornithine transcarbamylase deficiency 酶 Apert syndrome Cleidocranial dysplasia DiGeorge's syndrome DiGeorge's Homozygous familial hypercholesterolemia Fucosidosis PAH type PKU combine with Sucrase-isomaltase deficiency 苷 酶 49 Nemaline Rod Myopathy Nemaline Fibrodysplasia Ossificans Progressiva Menkes syndrome Menkes Fabry disease Fabry Prader-Willi syndrome Prader-Willi Niemann-Pick Niemann-Pick Tricho-hepato-enteric syndrome Collodion baby Harlequin ichthyosis A-3

35 58 Bullous Congenital ichthyosiform erythoderma Laron syndromelaron Dwarfism Laron Smith-lemli-opitz syndrome Smith-Lemli-Opitz Bardet-Biedl syndrome Bardet-Biedl Larsen syndrome Larsen Sialidosis Alstrom Syndrome Alstrom Chronic primary granulomatous disease Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) 67 Familial hyperchylomicronemia W A G R syndrome (Wilms tumor-aniridia-genitourinary W A G R Anomalies-mental Retardation) 69 Ectodermal Dysplasias Beckwith Wiedemann syndrome Beckwith Wiedemann Congenital insensitivity to pain with anhidrosis (CIPA) Wolfram syndromedidmoad Wolfram Adrenoleukodystrophy McCune Albright syndrome McCune Albright Crouzon syndrome Crouzon Thrombasthenia Schwartz Jampel syndrome Schwartz Jampel Fraser syndrome Fraser Mucolipidosis Ehlers Danlos syndrome IV Myotonic dystrophy Congenital Hyper IgE syndrome E Tyrosinemial I IIIII Hyperlysinemia Histidinemia A-4

36 86 3-Methylcrotony-CoA carboxylase deficiency 酶 A Multiple carboxylase deficiency 酶 Split-hand/ Split-foot malformation SHFM Metachromatic Leukodystrophy MLD Campomelic dysplasia with autosomal sex reversal MLD Osteopetrosis Carbohydrate-deficiency glycoprotein syndrome Trimethylaminuria Congenital generalized lipodystrophy A-5

37 () () () (RS)-2,3-bis (sulphanyl) propane-1-sulfonic acid (DMPS) sodium salt, Monohydrate (RS)-2,3-Dimercapto-1-propane sulfonic acid (DMPS), sodium salt, Monohydrate [Meso-2,3- dimercaptosuccinic acid, DMSA] Injection Capsule Capsule 100 mg /12/ /12/ () Agalsidase-alpha Injection alpha-galactosidase A deficiency (Fabry disease) () Agalsidase-beta Injection alpha-galactosidase A deficiency (Fabry disease) () Albendazole Tablet 200 mg (1) () Aldesleukin [RecombinantInterleukin-2] Injection 1.2mg/vial ( Metastatic renal cell carcinoma) (2) (Metastatic melanoma) ( 2001/03/30 ( ) A-6

38 () () Amphotericin B Lipid Complex Anagrelide Injection 5 mg/ml ( Capsule 0.5 mg; 1.0 mg () Antivenin of Vipera Russelli Injection ( ) Arginine ( ) Arsenic Trioxide ( ) Artemisinin ( ) Atovaquone-proguanil ( ) Benznidazole ( ) Betaine ( ) Bosentan Injection 10 gm/100ml Injection 1mg/ml,10ml/vial /2/ Tablet 100 mg Tablet 250 mg+100 mg Tablet 100 mg Powder for Reconstitution gm/scoopful 62.5 and 125 mg tablet A-7

39 ( ) Citrulline ( ) Cladribine ( ) Cycloserine ( ) Cysteamine Bitartrate ( ) Dantrolene ( ) Deferiprone (Kelfer) ( ) Diazoxide citrulline 2001/12/11 Tablet, 600 mg oral solution,1 g/10 ml Injection 1 mg/ml Capsule 250 mg citrulline 2001/12/ Capsule nephropathic cystinosis EQ 50 mg, 150 mg Base (Injection) 20 mg/vial Capsule 250 mg500 mg (Thalassemia major), Deferrioxamine ; (:, ),Deferrioxamine persistent hyperinsulinemic Capsule, Suspension hypoglycemia of infancy 50 mg; 50 mg/ml (PHHI) 1999/12/9(2 003/11/18 ) 2002/2/25 (250 mg) /2/25 (500 mg) A-8

40 ( ) Diloxanide Furoate Tablet 500 mg ( ) Dimercaprol Injection 10% ( ) Eflornithine HCL ( ) Epoprostenol ( ) Gabapentin ( ) Glatiramer acetate Injection 200 mg/vial Injection 0.5 mg base/vial; 1.5 mg base/vial /6/17(2002/ 11/14 ) Capsule; Tablet (Amyotrophic Laterol mg, 800 mg Sclerosis ALS) Injection 20 mg/vial (Multiple Sclerosis) ( ) Hemin Injection ( ) Iloprost nebuliser solution ( ) Imiglucerase ( ) Interferon-Beta-1a ( ) Interferon-Beta-1b A-9 Injection 200 units/vial (Type I) Injection (Multiple 3MIU6MIU Sclerosis) 12MIU/vial Injection 0.3 mg/vial (Multiple Sclerosis) /04/11 ( ( )

41 ( ) Interferon-Gamma 1b ( ) Iodoquinol Injection (Chronic mcg/0.5mlgranulomatous Disease) Tablet 210mg; 650 mg ( ) Ivermectin Tablet 6 mg ( ) L-5-hydroxytryptophan (5-HTP) Capsule ( ) Lactic acid bacteria oral use ( ) Laronidase ( ) Levocarnitine ( ) LiposomalAmphotericin B ( ) Meglumine Antimoniate 100 units/ml solution for infusion BH4 ( ) Tetrahydrobiopterin (BH4) deficiency PKU chronic pouchitis disease Injection; Oral Solution; Tablet [ 200 mg/ml, 1 Carnitine gm/10ml, 330 mg, 1gm] Injection 50 mg/ vial Injection (85 mg/ml) 2001/5/ ( ) /05/ (i) (tab) (t) A-10

42 ( ) Melarsoprol ( ) Metrifonate Tablet (3.6% solution propylene glycol) Tablet 30 mg ( )( ) ( ) Mitotane Tablet 500 mg ( ) Modafinil 200 mg ( ) Nifurtimox Tablet 30 mg;120mg; 250mg Narcolepsy <TD < td> ( ) Nitric Oxide Inhaler ( ) Oxamniquine Tablet 250 mg ( ) Paromomycin Sulfate Pentamidine ( ) Isethionate Capsule 250 mg [Injection] [300 mg/vial] (Pneumocystis carinii pneumonia; PCP) ( ( ) Phenytoin Capsule 30 mg ( ) ( ) Phosphate solution Solution [X-linked hypophospatemic Rickets] A-11

43 potassium acid phosphate + ( ) sodium acid phosphate,anhydrous Tablet [X-linked hypophospatemic Rickets] ( ) Primaquine-Phosphate [Tablet[26.3 mg] ( ) Proguanil Tablet 100 mg Pyrimethamine + ( ) Sulfadiazine Pyrimethamine + ( ) Sulfadoxine Pyrimethamine-sulfadoxinemefloquine ( ) ( ) Risedronate ( ) Sacrosidase ( ) Sod. Benzoate Sod. Benzoate & Sod. ( ) Phenylbutyrate Tablet 25mg+2gm Tablet 25 mg+500 mg Tablet 25 mg;250 mg; 500 mg Tablet 30 mg Oral Solution 900 IU/ml Capsule [250 mg] [Oral Solution; Injection ] [ 100mg/ml+100mg/ml, 100ml/vial ] Primary Paget disease PKU with congenital sucrase-isomaltase deficiency Non-ketotic hyperglycinemia /3/ A-12

44 Sodium ( ) Phenylbutyrate [Powder; Tablet] [3 gm /teaspoonful; 500 mg] carbamylphosphate synthetase (CPS), Ornithine transcarbamylase (OTC)Argininosuccinic synthetase (AS) ( ) Sodium Stibogluconat Injection 100 mg/ml, 100 ml/bot ( ) ( ) Suramin Tetrahydro- ( ) Biopterin(BH4) Injection 1 g/vial Tablet Terahydrobiopterin 10 and 50 mg ( ) Thalidomide Capsule 50 mg leprosum ( ) Thymosin alfa 1 injection DiGeorge Syndrome Thyrotropin alfa ( ) Injection TPN for PKU with congenital ( ) sucrase-somaltase Injection deficiency [Injection] [1.1mg/ml] TPN For PKU with congenital sucrase-isomaltase deficiency A /10/

45 TPN for PKU with congenital ( ) sucrase-somaltase Injection deficiency TPN For PKU with congenital sucrase-isomaltase deficiency ( ) treprostinil sodium Injection 1.0, 2.5, 5.0, 10.0 mg/ml ( ) Tretinoin soft gelatin capsules 10 mg ( ) Trientine Hcl [Capsule] [250 mg] (Wilson Disease) ( ) Zinc Acetate [Capsule] [25-50 mg] (Wilson Disease) A-14

46 / 5-HTP 100MG CCP Aldurazyme 500U/2.9m g/5ml alpha-glucosida 50 mg/vial Genzyme se Anagrelide (Agrylin) Arsenic Trioxide inj (Asadin) 0.5mg / cap 1mg/ml 10ml/vial Beta-galactosida se A 35mg/vial (Fabrazyme) Mallinckro dt(shire) Asadin 93 2 Tung Yang 26 2 A-15

47 Beta-galactosida se A 35mg/vial (Fabrazyme) / Fabry s Disease alpha-galacto sidase A deficiency (Fabry disease) 68 3 Genzyme Betaine Twin Carnitene for inj 1G/AMP Carnitine tab 1g 1tab tid-qid tab tid Short chainacyl-co A, dehydorgenas e deficiency Glutaric aciduria type I 1tab bid-qid MMC deficiency qd-bi d 025-1tab qd-tid tab tid-qid MMC deficiency MMC deficiency propionic acidemia, 1tab qd 84 1 Metabolic CNS disease A-16

48 / 0.25tab qd Amino acid disorder Carnitine tab 1g Citrulline solin Cystagon Dantrolene (Dantrolen) 0.33tab tid Fatty Acid Oxidation Defect 0.33tab bid carnitine deficiency 1tab qid MELAS 0.5tab qd g/10ml 0.2pkg qd 150mg /cap 4cap qid 20mg/vial Glutaric aciduria type I Ornithine transcarbamy lase deficiency intermediate cystinosis Procter & 10 1 Gamble Deferiprone (Kelfer) 500mg / cap 810 1, Deferrioxami ne ; (:,... ), Deferrioxami ne A-17

49 / Deferiprone (Kelfer) 500mg / cap Diazoxide oral susp. (Proglycem) 50mg/ml 30ml / btl 1. edema, Lasix PHHI 2. (persistent Hirsutism: face, hyperinsuline 9 1 neck, back and mic extremities. hypoglycemi a of infancy) Nesidiodlasto sis protein induced hyperinsuline mia 4 1 Flolan 500mcg/vial Heme arginate (Normosang) Iloprost inj (Ilomedin-20) 250mg/amp 25mg/ml 10ml/amp 20mcg/1ml/ amp Glaxo Wellcome Leiras medica A-18

50 Iloprost inj (Ilomedin-20) Imiglucerase (Cerezyme) / 20mcg/1ml/ amp 200u/vial Schering AG Gaucher s Disease Gaucher disease Imukin for inj 100mcg/vial Interferon beta-1a (Rebif) 22mcg/ 44MCG Genzyme Therapeuti cs Boehringer Ingelheim Vetter Pharm(Ser ono) Indus. Farma. Serono 10 1 Multiple sclerosis Multiple Sclerosis Joulie solution 500ml/btl NTUH A-19

51 / 700mg/tab X-linked Hypophosphat emic rickets 250mg 1tab qid Familial hypophatemic rickets X-linked hypophosphate mic rickets K-Phos No.2 Low 250mg 2tab Phosphorus tid Rickets and Osteomalacia 250mg 1.5-2tab X-linked hypophosphate tid-qid mic rickets X-linked 250mg hypophosphate 1-2tab qid mic rickets Levocarnitine 1gm/tab Carnitine Bristol-My ers Lysodren mg/tab (Mitotane) Modafinil 200 mg / tab Narcolepsy A-20

52 Phenylbutyrate (Buphenyl) / 500mg 1-2.5cap q12h-q6h 500mg 1-1.5cap qd-bid 500mg 1captid-bid 500mg 1cap q6h-bid 500mg 0.5cap tid 500mg/tab OTC deficiency Urea cycle defect Argininosuc cinic acidemia 4 1 Propionic acidemia citrullinemi a, Ucyclyd Phosphate solution 500cc/B 91 4 Potassium acid phoasphate+sod ium acid Tablet phosphate anhydrous Proglycem 30ML 99 5 Schering Plough Replagal 3.5MG/3.5 Chesapeake 72 1 ML/VIAL Biologica Non-ketotic hyperglycin Sodium 250mg / cap emia Benzoate UBI (Merck) Stimol oral solution 1G/10ML Biocodex A-21

53 Tetrahydrobiopte 10MG rin(bh4) Thado (Thalidomide) / 50mg/cap Thyrogen Thyrotropin alfa,2vials/set 1mg/vial Schircks Lab.,, Tung-Yang MMHCC Skin rash with itching Erythematous papule with itching1 1.1mg/inj Genzyme Nausea and vomiting Tracleer 62.5mg/tab Patheon Tretinoin (Vesanoid) mg/cap ATRA Retinoid syndrome1 APL (skinliver ) Trientine 250mg /cap Wilson diseasse A-22

54 / VSL# Zinc acetate (Galzin) Pharmaceu ticals Wilson 50mg/cap diseasse Teva 25mg/cap Teva A-23

55 HTP (Oxitriptan) agalsidase beta (Fabrazyme) Agrylin (Anagrelide) Aldesleukin [Recombinant Interleukin-2] (Proleukin) Aldurazyme (Laronidase) alfa-galactosidase A (Replagal) Alpha-glucosidase Amphotericin B-liposome Arsenic trioxide (Asadin) Betain / 100mg/cap % % cap/ % 35mg/vial % % 0.5mg cap % % 18MIU/vial, mg/vial % 3.5mg/3.5ml /vial % 50mg/vial % 50mg/vial % % 10mg/10ml/ vial % A-24

56 BH4 (Tetrahydrobiopterin) Buphenyl (sodium phenylbutyrate) Buphenyl (sodium phenylbutyrate) Carnitene for inj Cerezyme (imiglucerase) citrulline malate Creatine Cystadane (Betaine anhydrous) cysteamine bitartrate (Cystagon) Dantrolene sodium Deferiprone (Kelfer) / 10mg/tab 500mg tab 250mg tab 1g/amp 200u/vial 1gm/10ml % 70.74% % % % % % % mg/cap 91 0, 1200mg/ g/vial, 180g/bottle 150mg/cap 20mg/vial 500mg/cap % % % % % A-25

57 Diazoxide (proglycem) 50mg/ml, 30ml/btl Flolan (Epoprostenol) Glycine Ilomedin-20 (Iloprost, prostacyclin PGI2 Imukin (Interferon gamma 1b) Imukin (Interferon gamma 1b) Interferon Beta 1b (Betaferon) Interferon-Beta 1a (Rebif) Interferon-Beta 1a (Rebif) Kphos NO.2 tablet(potassium acid phosphate 350 mg+sodium acid phosphate anhydrous 700mg) / % 56.08% % 46.47% 500mcg/vial mcg/vial mg/tab 20mcg/ml/a mp 100mcg/0.5 ml/vial 0.1mg/vial 0.3mg/vial 22mcg 5MIU/vial 44mcg 12MIU/vial 100tab/ % % % % % % % % A-26

58 Lactic acid bacteria L-carnitine Levocarnitin oral solution Lysodren (Mitotane) Normosang (Heme arginate) Normosang (Heme arginate) Phenytoin Phosphate solution Provigil (Modafinil) Sacrosidase; oral solution Sodium Benzoate / % 1gm/tab % % 1gm/10ml/b ot % 9.11% 500mg tab % 250mg/amp mg/ml, ml/amp % % 30mg/cap % % % 200mg tab % % 900IU/ml % 44.35% 250mg/cap A-27

59 THADO (thalidomide) 50mg/cap Thyrogen (thyrotropin alfa) Tracleer (Bosentan) Tracleer (Bosentan) Trientine (Syprine) Zinc Acetate (Galzin) Zinc Acetate (Galzin) Zinc Acetate (Galzin) / 1.1mg/vial, 2vials/set 62.5mg/tab, 60tab/ 125mg/tab 250mg/cap 25mg/cap 250cap/ 50mg/cap % % % 35.14% % % % A-28

60 1 PK AID-4 Fructose Modjul Calogen Phlexy-Vits ( ) SUCRAID 2 I-Valex-2 3 Glutarex-2 TYPE2 A-29 4 Low Met Product 5 MSUD powder 6 Lofenalac 7 Phenyl-free 8 OS1 (Milupa) 9 UCD1 10 LEU1 (Milupa) 11 Hominex-2 12 Prosobee 13 Glutares-1 TYPE1 14 Ketonex-1 15 Provimin TYPE2 Medium Chain Triglyceride Portagen Powder 16 Alfare Generaid Plus 17 Xlys low try abalog TYPE1 18 SHS(Xmet, Cys Maxamaid) 19 Product Aaginine 21 OS1 OS2 22 UCD1 UCD2

61 PKU Phenex-1 Pheny1ketonuria Phenylalanine Free PKU2 24 PKU3 Phenex-2 Low Met Product XMET Analog1 25 XMET Maxamaid1 Xmet Xcys Analog1 Hominex-11 1 Pheny1ketonuria Hypermethionemia S-20 MSUD11 MSUD21 26 MSUD Analog1 MSUD Maxamaid1 Ketonex-21 OS11 Maple Syrup Urine Disease OS21 XMTVI Analog1 27 Methylmalonic AciduriaPropionic XMTVI Maxamaid1 Acidemia) Propimex-11 Propimex-21 LEU11 LEU21 28 XLeu Analog1 3-Hydroxy-3-methyl-glutaric acidemia Xleu Maxamaid1 UCD11 UCD21 29 Cyclinex-11 Cyclinex-21 Urea Cycle Disorder A-30

62 TYR11 TYR21 XPHEN TYR Analog1 A-31 XPXT MAXAMAID UNFLAV(1-8 ) 30 XPHEN TYR MAXAMUM8 Hereditary Tyrosinermia XPTM TYROSIDOM Tyromex-1 Tyromex-2 HOM11 HOM21 HOM11 HOM21 31 XMET Analog1 XMET Maxamaid1 Hominex-11 Hominex-21 Homocystinuria LYS11 32 LYS21 Organic Acidemia-Hyperlysinemia GA11, 33 GA21 Glutaric Acidurua, Type1 XlysLowTyrMaxamaid1 34 Glutarex-2, Glutaric Acidurua, Type Valex-11 Isovaleric Acidemia Energivt 36 Pro-Phree Amino Acid Metabolic Disorder Leucine lsoleucine Valine 37 Citrulline Glycine Esential Amino Acid Glutamic Acid Amino Acid Metabolic Disorder

63 38 Lorenenzo s oil 39 Generaid Plus Adrenal Leukodystrophy Inborn errers ofbile acid synthesis Neocate Neocate Advance Tricho-hepato-enteric syndrome A-32

64 58 1 X X ( ) Ucephan Oral Solution 100ml/bot Proglycem 50mg/ml 30ml/bot ( ) 10%Sod. Benzoate+10%Sod. Phenylacetate Diazoxide 50mg/ml,30ml/bot / / (Nesidioblastosis) 41 3 X Lysodren Tab Mitotane 500mg / Sodium Phenylbutyrate 59 4 X Buphenyl Tab 500mg / 500mg 19 5 X Dantrolene 20mg IV Dantrolene 20mg 48 6 X Dilantin 30mg Cap Phenytoin 30mg 1. ( Procter & Gamble ) / ( ) / A-33

65 30 7 X Betaferon Inj 0.3mg/2ml/ vial 36 8 X Cartnitene 1gm Tab 29 9 X Cerezyme Inj X Rebif Inj 3MIU X Rebif Inj 6MIU X D2 Thyrogen Inj X Betaine HCL withpepsin Cap Interferon B-1b 0.3mg/vial Levocanitine chew. Tab. 1gm Imiglucerase 200Unit/vial Interferon beta-1a INJ 3MIU Interferon beta-1a INJ 6MIU Thyrotrophin alfa 1.1mg Betaine HCL 648mg with Pepsin NF(1:10000) 130mg A / 2. (Mutiple Sclerosis) / Carnitine TYPE 1 / (Gaucher's disease) / (Mutiple Sclerosis) / (Mutiple Sclerosis) / /

66 56 14 X Sucraid Oral Solution X Flolan Inj X Imukin Inj X X Syprine(Trientine HCl 250mg/Cap.) Sacrosidase PKU eith congenital 8500IU/ml,118ml/ sucrase-isomaltase bot deficiency Epoprostenol 500mcg/vial Interferon gamma-1b 100mcg (3MIU)/0.5ml /vial Trientine HCl 250mg Sodium Benzoate Cap. Sodium Benzoate 250mg 250mg ( ) X Cystagon Cap 150mg Cysteamine Bitartrate 150mg / / (Chronic / Granulomatous Disease) / (Wilson Disease) Non-Ketotic hyperglycinemia Nephropathic Cystinosis 8 20 X Anagrelide 0.5mg Cap Anagrelide 0.5mg X Tetrahydro-Biopterin (BH4) 10mg Cap Tetrahydro-Biopter in (BH4) 10mg / / / Tetrahydrobiopterin / X Cycloserine 250mg cap Cycloserine 250mg / A-35

67 20 23 X Kelfer Cap. 500mg X X X X X Levocarnitin Oral Solution Zinc Acetate 25mg/cap Zinc Acetate 50mg/cap L-Arginine HCl Inj 30ml/vial Stimol (Citrulline 1gm/10ml/sachet) Deferiprone- L1 500mg Carnitin-Levo 1gm/10ml/bot Zinc Acetate 25mg Zinc Acetate 50mg L-Arginine HCl Inj. 250mg/ml Citrulline 1gm/10ml Deferioxamine ; (, / ), Deferioxamine Thalassemia major Carnitine / (Wilson Disease) / (Wilson Disease) / Citrulline ( V ) A-36

68 28 29 X X Normosang inj (Human Hemin 25mg/ml 10ml/amp) Copaxone Inj 20mg Heme Arginate 25mg/ml ml/amp / Glatiramer acetate 20mg / (Mutiple Sclerosis) X Provigil Modafinil 200mg Y E Y A K W X REBIF INJ 44MCG REBIF INJ 22MCG Sodium Benzoate Cap. 250mg Fabrazyme 35mg Inj. Interferon beta-1a INJ 44MCG(=12MIU) Interferon beta-1a INJ 22MCG(=6MIU) Sodium Benzoate 250mg Agalsidase beta 35mg 5 34 X Zadaxin Inj 1.6mg Replagal 3.5mg Inj (Mutiple Sclerosis) (Mutiple Sclerosis) (Non-Ketotic / hyperglycinemia) alpha-galactosidase A deficiency / 0 (Fabrazyme disease) alpha-galactosidase A deficiency (Fabrazyme disease) A-37

69 10 35 W Asadin Inj. 1mg/ml 10ml Arsenic Trioxide 1mg/ml V Stimol oral Solution Citrulline malate 1g/10ml 1g/10ml X Zadaxin Inj. Thymosin alpha-1 1.6mg X Carnitene inj. 1gm Canitine-Levo 1gm (RS)-2,3Bis(Sulphanyl )Propane-1-Sulphonic 2 38 V Dimaval Inj. Solution acid, Sodium salt-(monohydrate) 50mg Sodium-2,3-Dimercapt 1 39 V Dimaval Capsules o-1-propane Sulfonate (Monohydrate) 100mg 40 X Ilomedium-20 inj Iloprost 20mcg/ml Citrulline (Lab. Biocodex) DiGeorge syn Carnitine /Sigma-tau /Sigma-tau ( /Heinz Haupt ) Chemischpharmazeutische Fabrik Gmbh & Co. KG / A-38

70 41 X K-Phos No.2(Beach Pharmaceuticals) Potassium acid phosphate 305mg Sodium acid phosphate anhydrous 700mg 42 X Virazole I.V. 12ml Ribavirin 100mg/ml 18 V Carnitene 1g chewable tablets Canitine-Levo (inner salt) 1gm 43 A HTP Oxitriptin 100mg 44 X X VSL#3 450 billion bacteria/packet Cystadane powder for oral sol n 1gm/scoopful (Betaine anhydrous) Lactic acid bacteria 450 billion bacteria Betaine anhydrous 180gm / SARS /ICN 0 Pharmaceuticals,Inc Carnitine /Sigma-tau BH4 Chronic pouchitis disease /VSL Pharmaceuticals, Inc. /Orphan Medical, Inc. A-39

71 ICD-9-CM ( ) ICD-9-CM 01 Urea cycle disorders Citrullinemia Amino acid metabolic disorders ( Aminoacidopathies) Homocystinuria Hypermethioninemia Cystinosis Nonketotic hyperglycinemia Phenylketonuria Tetrahydrobiopterin deficiency Hereditary tyrosinemia Maple syrup urine disease Hereditary coproporphyria Multiple sclerosis Gaucher's disease Wilson's disease Nesidioblastosis Amyotrophic lateral sclerosis (ALS) Organic acidemias Isovaleric acidemia Glutaric aciduria type I, II Propionic acidemia Methylmalonic acidemia Hydroxy-3-methyl-glutaric acidemia Galactosemia Fatty acid oxidation defect Carnitine deficiency syndrome, primary A-40

72 ICD-9-CM 12 Mitochondrial defect Kearns-Sayre syndrome Kearns-Sayre Leigh disease Leigh MELAS MELAS Mitochondrial Neurogastrointestinal MNGIE Encephalopathy Syndrome 13 Aarskog-Scott syndrome Aarskog-Scott Achondroplasia Angelman syndrome Angelman Ataxia telangiectasia Cockayne syndrome Cockayne Duchenne muscular dystrophy Glycogen storage disease GM1/GM2 gangliosidosis GM1/GM Hereditary epidermolysis bullosa Huntington disease Huntington's chorea) Hutchinson Gilford progeria syndrome 24 Ichthyosis, lamellar recessive Kenny-Caffey syndrome Kenny-Caffey Lesch-Nyhan syndrome Lesch-Nyhan Lowe syndrome Lowe Mucopolysaccharidoses Osteogenesis imperfecta Pseudohypoparathyroidism Rett syndrome Spinal muscular atrophy Spinocerebellar ataxia Sulfite oxidase deficiency? Thalassemia major Tuberous sclerosis Waardenburg syndrome A-41

73 A-42 ICD-9-CM 38 X-linked hypophosphatemic rickets Zellweger syndrome Zellweger Progressive intrahepatic cholestasispfic Inborn errors of bile acid synthesis Primary Paget disease Nitroacetylglutamate synthetase deficiency NAG synthetase deficiency Omithine transcarbamylase deficiencyy? 270.6? Apert syndrome Cleidocranial dysplasia DiGeorge s syndrome DiGeorge s Homozygous familial hypercholesterolemia Fucosidosis PAH type PKU combine with Sucrase-isomaltase deficiency 酶 酶 Nemaline Rod Myopathy Nemaline Fibrodysplasia Ossificans Progressiva Menkes syndrome Menkes Fabry disease Fabry Prader-Willi syndrome Prader-Willi Niemann-Pick disease Niemann-Pick Tricho-hepato-enteric syndrome Collodion baby Harlequin ichthyosis Bullous Congenital ichthyosiform erythodermaepidermolytic hyperkeratosis Laron syndromelaron Dwarfism Laron Smith-Lemli-Opitz syndrome Smith-Lemli-Opitz

74 ICD-9-CM 61 Bardet-Biedl syndrome Bardet-Biedl Larsen syndrome Larsen Sialidosis Alstrom Syndrome Alstrom Chronic primary granulomatous disease Persistent hyperinsulinemic hypoglycemia of infancyphhi 67 Familial hyperchylomicronemia W A G R syndromewilms tumor-aniridia-genitourinary W A G R Anomalies-mental Retardation 69 Ectodermal Dysplasias Beckwith Wiedemann syndrome Beckwith Wiedemann Congenital insensitivity to pain with anhidrosiscipa Wolfram syndromedidmoad Wolfram Adrenoleukodystrophy McCune Albright syndrome McCune Albright Crouzon syndrome Crouzon Thrombasthenia Schwartz Jampel syndrome Schwartz Jampel Fraser syndrome Fraser Mucolipidosis Ehlers Danlos syndrome IV Myotonic dystrophy Congenital Hyper IgE syndrome E Tyrosinemial I IIIII Hyperlysinemia Histidinemia Methylcrotony-CoA carboxylase deficiency 酶 A Multiple carboxylase deficiency 酶 A-43

75 Split-hand/ Split-foot malformation SHFM Metachromatic Leukodystrophy MLD Campomelic dysplasia with autosomal sex reversal ICD-9-CM Hand Foot MLD Osteopetrosis Carbohydrate-deficiency glycoprotein syndrome Trimethylaminuria Congenital generalized lipodystrophy A-44

76 (* ) A-45 苷 酶 (full Crigler-Najjor syndrome Ext3880 6,000(/ ) (EDTA seguence of UDP-glucuronosyl type1and 2 )1-2 transferase A1 gene) (mutrtion of multidrug Dubin-Johnsonsyndrome Ext3880 6,000(/ ) (EDTA resistance protein gene )1-2 MRP2gene) G6PD G6PD G6PD Ext3880 1,000(/ ) (EDTA G6PD )1-2 Urine Organic Acid Analysis (GC/MS) ( Organic Aciduria ) Ext2349 2,000(/ ) Plasma/UrineAmino AcidA nalysis Ext2349 2,000(/ ) MPS Ext2349 (GAG) 500(/ )

77 (* ) 酶 酶 ( Ext2349 1,000-2,000/ (/ ) ) Ur. Test Plasma CarnitineAnalysis Primary or secondary Carnitine deficiency A ( Ext2349 / ) 500( Ext2349 / ) 2,000/ GC/MS Ext2349 (/ ) αβ thalassemi Ext7147 / 3,000(/ ) (DMD-BMD) Ext7147 1,500

78 Inborn enm ScreeningUrine Capillary microscopy SclerodemaDermatomyositis AA ( CSF) urine organic acid( ) α1- 酶 α1-antitrypsin ceruloplasmin( ) A-47 (* ) 3,500/ Ext5004 (/ ) Ext Ext Ext4402 (2,000 ) Ext4402 (1,800 ) Ext (/ ) Ext (/ ) VLCFA C22C24C26 ASSAY Ext4402 2,000(/ ) (very-long-chain-fatty)( )

79 (* ) carnitine Ext4402 1,200(/ ) carnitine( ) Fragiles X syndrome PCR screening Genetic Epilepsy: SCN1a, SCN 1b,CHRNA4,KCNQ2, KCNQ3Very Long Chain CoA Dehydrogenase Medium Chain CoA Dehydrogenase Short Chain CoA Dehydrogenase LCHAD Primary Carnitine Deficiency(OCTN2) CARNITINE PALMITOYLTRANSFEERASE II Mitochondril DNA Mutetion screening Point mutation 3243,8344,8993,9176 Common deletion Rett syndromecdg Type I AadrenoleukodystrophyMenkes disease Maple syrup urine disease E1a,E1b,E Ext4402 A-48

80 (* ) Lesch-Nyhan SyndromeSoulfiete Oxidase Glycogen Storeage Disease Type 1a Androgen Receptor gene Low Density Lipoprotein Receptor Gene Alagille syndrome ORW Type II Long QT syndrome: SCN5a, Kvlqt1, Mink Townes Brocks Syndrome Osteropetrosis, autosomal recessive Denys-Drash syndrome(wt1 gene) Glutaric acduria Type 1 Spondylepiphyseal dysplasia tarda Ext4402 Muscle Biopsy ( ) Electron microscope(muscle) Ext5908 2,500(/ ) ( ) Ext5740 5,000(/ ) A-49

81 ( ) ( )( ) (* ) Ext (/ ) Ext4435 2,500(/ ) Ext4435 3,000-5,000(/ ) A-50 ( ) Ext4435 2,500(/ ) Mechylation PCR Southern blot FISH ANAC(Anti-neutrophil cytoplasmic antibody) Prader-Willi syndrome Angelman syndrome Fragile-X syndrome Degeorge syndrome Williams syndrome Prader-Willi syndrome Angelman syndrome Miller-Dieker syndrome Smich-Magenis yndrome Wegener s granulomatosis Microscopic polyangiitis Churg-Strauss syndrome Ext Ext3635 1,000(/ ) ( ) Ext (/ )

82 Anti-glomerularbasement membrane AB Goodpasture syndrome (* ) ( ) 300(/ ) Ext2651 ( 12066AA) A-51 X 200(/ 30 PCR ( Ext2619 )1,000(/ ) ) Fragile X Syndrome, Huntington 1. Chorea, SCA, Mitochondria Disease (Deafness, MELAS, Ext6702 1,500(/ ) MERRF, LHON), Kennedy s 2. Disease, GSDIa, SRY X A Ext6702 2,340(/ ) (GC-Mass) 2. X A Ext6702 2,600(/ ) 2. X Ext6702 1,000(/ ) X0014

83 -Iduronidase I (MPS I) Iduronate 2-sulfatase II (MPS II) N-Acetyl-D-Glucosaminidas e IIIB (MPSIIIB) N-Acetyl-Galactosaminidase 6-sulfatase IVA (MPS IVA) -Galactosidase IVB GM1 (MPS IVB) Arylsulfase B VI (MPS VI) (* ) Ext6702 2,500(/ ) X Ext6702 8,000(/ ) X Ext6702 2,550(/ ) X Ext6702 6,400(/ ) X Ext6702 2,500(/ ) X Ext6702 2,500(/ ) X0025 Arylsulfatase A Ext6702 2,500(/ ) X0027 (MLD) Glucose-6-Phosphatase Ia Ext6702 4,000(/ ) X0028 (GSDIa) A-52

84 A-53 (* ) -Glucosidase II Ext6702 3,100(/ ) (Pompe s Disease) (Pompe s Disease) X0029 -Fucosidase Fucosidosis -Glucosidase (Gaucher s Disease) Phe PKU Phenylketonuria(PKU) DHPR ( ) Pterins HPLC ( ) PKU Ext6702 3,300(/ ) X Ext6702 2,750(/ ) X Galactose & Galactose-1-Phosphate Galactosemia Gal -1-P uridyl-transferase Galactosemia Fibroblast 14C-propionate incorporation Porpionic Propionyl CoA carboxylase acidemia(pa) (PCC)

85 (* ) Fibroblast 14C-propionate incorporation Methylmalonic acidemia(mma) mutase MUT α-galactosidse A Fabry s disease Fabry s Fabry s disease β-hexosaminidase A Tay-Sachs disease β-hexosaminidase B Sandhoff disease β-glucosidase Gaucher s disease ( ) Arylsulaftase A Metachromatic leukodystrophy A-54

86 Mucopolysaccharidosis VI Arylsulaftase B (MPS VI) β-glucuronidase β-glucuronidase deficiency α- mannosidase Mannosidosis α- glucosidase Pompe s disease (* ) A-55 Acute intermittent prophyria PBG deaminase (AIP) (PA) (MMA) (MSUD)MCADIsovaleric aciduria

87 A-56 (* ) acylcarnitines (PA) (MMA)MCAD Isovaleric aciduriascad Homocystinineuria (HCU) MSUDPKUTyrosinenemia Ext7048 3,500(/ ) 2.DiGeorge syndrome 3.Williams syndrome Ext7048 (FISH) 4.Kallmanns syndrome 5,500(/ ) 5.Prader-Willi syndrome 6.Angelman syndrome Mutational analysis Ext7055 ofcyp21 gen 1,500(/ ) 綉 HLA-DQA1,HLA-DQB1 genotyping Apolipoprotein Egenotyping Genotyping Lipoprotein Ext7055 綉 2,000(/ ) Ext7055 綉 1,000(/ )

88 Mutational analysis ofp53 gene(exon 5~exon 8) Mutational analysis ofk-ras gene α-thalassemia gene β-thalassemia gene bcr-abl gene PML-RAR gene PCR-STR (D3S1358,Vwa,FGA, Amelogenin,D8S1179,D21S11, D18S51,D55S818,D13S317,D7 S820) SMN gene analysis Dystrophin immunostaining 17-OHP,TSH,T3,T4,Free T4,ACTH,Cortisol, AldosteronePRA,PTH,Insulin etc. Cancer Cancer α-thalassemia β-thalassemia cancer Spinal muscular atroply DMD SMA (* ) Ext7055 綉 2,000(/ ) Ext7055 綉 1,500(/ ) Ext7071 3,300(/ ) Ext7071 9,000(/ ) Ext6486, Ext6755 (CAH) Ext7150 (CHT) 2,500(/ ) A-57

89 PhenylpyruvateAlpha-keto acid (* ) Ferric Chloride Test (FCT) 2,4-Dinitrophenylhydrazine Compound with disulfide linkage (DNPH) Mucopolysaccharides Cyanide Nitroprusside (CNP) Glycosaminoglycans Ext (/ ) Benedict s Test (RS) Reducing Substances Para-Nitroaniline Test (PNA) Methylmalonic acid Nitronaphthol Test (NNT) Ethylmalonic acid p-hydroxyphenolic acid deridatives Homocystinineuria (HCU), MSUD, PKU, (Blood amino acids analysis- Tyrosinenemia, Ext1561 2,500(/ ) LC/MS/MS) Argininosuccinase deficiency acidemia (PPA), Methylmalonic aciduria (Blood acylcarnitine (MMA), Glutaric aciduria analysis- LC/MS/MS) Type 1 and 2, Isovaleric acidemia, SCAD, MCAD, LCAD, Translocase Propionic Ext1561 A-58 2,000(/ )

90 (* ) Propionic acidemia (PPA), Methylmalonic aciduria (MMA), (Urine organic acid Ext1561 2,000(/ ) Glutaric aciduria Type 1 and 2, analysis- GC/MS) Isovaleric acidemia, SCAD Cleidocranial dysplasia (DNA full sequence) Glutaric aciduria type I (DNA full sequence) Glycogen storage disease typr Ia (DNA full sequence) (GSDIa) GM1-gangliosidosis (DNA full sequence) Hereditary hemorrhagic telangiectasia (HHT) (DNA full sequence) type I and II (Osler-Rendu-Weber disease) A-59 * Ext ** Ext Ext Ext Ext /9

91 HMG-CoA lyase deficiency (DNA full sequence) Isovaleric aciduria type I (DNA full sequence) MPS IVA (DNA full sequence) MPS VI (DNA full sequence) Multiple exostoses type I and II (DNA full sequence) Pelizaeus-Merzbacher disease/ X-Linked Spastic (Gene quantity analysis) Paraplegia Retinopigmemtosa (X-linked, XRP2) (DNA full sequence) Spondylocostal dysostosis (DNA full sequence) Thyroid peroxidase deficiency (TPO) (DNA full sequence) Type I Oculocutaneous Albinism (OCAI) (DNA full sequence) Von Hippel-Lindau disease (DNA full sequence) X-linked juvenile retinoschisis (DNA full sequence) (* ) Ext Ext Ext Ext Ext / Ext Ext Ext Ext Ext Ext Ext A-60

92 X-linked recessive spondyloepiphyseal (DNA full sequence) dysplasia tarda Spinal muscular atrophy (Gene quantity analysis) (DNA mutation hot spot analysis- restriction Achondroplasia enzyme digestion) (DNA mutation hot spot analysis- restriction Apert syndrome enzyme digestion) (DNA mutation hot spot analysis- restriction Gaucher s disease enzyme digestion) (DNA mutation hot spot analysis- restriction GSDII (Pompe disease) enzyme digestion) (DNA mutation hot spot analysis- restriction Hypochondroplasia enzyme digestion) (DNA short tandem repeat analysis- PCR base) Fragile X Huntington disease (DNA short tandem repeat analysis- PCR base) (* ) Ext Ext Ext Ext Ext Ext Ext Ext Ext A-61

93 (DNA short tandem repeat Myotonic dystrophy analysis- PCR base) Spinocerebellar ataxia (SCA1, SCA2, SCA3, (DNA short tandem repeat DRPLA, SCA6, SCA7) analysis- PCR base) Adrenoleukodystrophy (Linkage Analysis) Autosomal dominant polycystic kidney (Linkage Analysis) disease (ADPKD) type I and II Congenital heart disease (Linkage Analysis) Duchenne / Becker muscular dystrophy (Linkage Analysis) (D/BMD) Ectodermal dysplasia (Linkage Analysis) Greig-cephalopolysyndactyly syndrome (Linkage Analysis) Hereditary hemorrhagic telangiectasia (HHT) type I and II (Linkage Analysis) (Osler-Rendu-Weber disease) Lesch-Nyhan (Linkage Analysis) (* ) Ext Ext Ext Ext Ext Ext Ext Ext Ext Ext A-62

94 Lissencephaly syndrome (Linkage Analysis) Multiple exostoses type I and II (Linkage Analysis) Prader-Willi syndrome (Linkage Analysis) Retinopigmemtosa (Linkage Analysis) (RP2, 3, 4, 6, 11, 14, 19) Wilson disease (Linkage Analysis) Wolf-Hirschhorn (4p deletion) syndrome (Linkage Analysis) Antley Bixler syndrome (DNA partial sequence) Crouzon syndrome (DNA partial sequence) Cystic fibrosis (DNA partial sequence) Nonspecific craniosynostosis (DNA partial sequence) Pfeiffer syndrome (DNA partial sequence) (* ) Ext Ext Ext Ext Ext Ext Ext Ext Ext Ext Ext A-63

95 Skeletal dysplasia (DNA partial sequence) Thanatophoric dysplasia (DNA partial sequence) (* ) Ext Ext A-64