Practical Developments in Inherited Metabolic Disease: DNA Analysis, Phenylketonuria and Screening for Congenital Adrenal Hyperplasia: Proceedings of the 23rd Annual Symposium of the SSIEM, Liverpool, September 1985

345 Pages·1986·10.115 MB·English

by  J. Scott (auth.), G. M. Addison, R. A. Harkness, D. M. Isherwood, R. J. Pollitt (eds.)

Practical Developments
in Inherited Metabolic Disease
Practical Developments in
Inherited Metabolic Disease:
DNA Analysis,
Phenylketonuria and
Screening for Congenital
Adrenal Hyperplasia
Proceedings of the 23rd Annual
Symposium of the SSIEM,
Liverpool, September 1985
The combined supplements of Journal of Inherited Metabolic
Disease Volume 9 (1986)
edited by G. M. Addison,
R. A. Harkness,
D. M. Isherwood and R. J. Pollitt
~MTP PRESS LIMITED
~a ,~
member of the KLUWER ACADEMIC PUBLISHERS GROUP
LANCASTER / BOSTON / THE HAGUE / DORDRECHT
Published in the UK and Europe by
MTP Press Limited
Falcon House
Lancaster, England
British Library Cataloguing in Publication Data
Practical developments in inherited metabolic disease: DNA
analysis, phenylketonuria and screening for congenital
adrenal hyperplasia.
1. Metabolism, Inborn errors of
I. Addison, G. M.
616.3'9042 RC627.8
ISBN -13: 978-94-010-8332-4 e-ISBN-13: 978-94-009-4131-1
DOl: 10.1007/978-94-009-4131-1
Published in the USA by
MTP Press
A division of Kluwer Academic Publishers
101 Philip Drive
Norwell, MA 02061, USA
Library of Congress Cataloging in Publication Data
Practical developments in inherited metabolic disease.
"The combined supplements of Journal of inherited metabolic
disease, volume 9 (1986)."
Based on papers presented at the 23rd Annual Symposium of
the SSIEM, held in Liverpool in 1985.
Includes bibliographies and index.
1. Metabolism, Inborn errors of- Congresses.
2. Phenylketonuria-Congresses. 3. Adrenogenital syndrome
-Diagnosis-Congresses. 4. Deoxribonucleic acid-Analysis
-Congresses. I. Addison, G. M. (Gerald Michael)
II. Society for the Study of Inborn Errors of Metabolism.
Symposium (23rd : 1985 : Liverpool, Merseyside) III. Journal
of inherited metabolic disease. [DNLM: 1. Adrenal Hyperplasia,
Congenital--diagnosis---congresses. 2. DNA-analysis
congresses. 3. Metabolism, Inborn Errors-congresses.
4. Phenylketonuria-congresses. W3 S05915K 23rd 1985 /
WD 205 P895 1985]
RC627.8.P73 1986 616.3'9043 86-20860
ISBN -13: 978-94-010-8332-4
Copyright © 1986 SSIEM and MTP Press Limited
Softcover reprint of the hardcover 1st edition 1986
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted in any form or by any
means, electronic, mechanical, photocopying, recording or
otherwise, without prior permission from the publishers.
Contents
Author Index ix
Title Index xi
The 23rd Annual Symposium of the SSIEM: Liverpool 1985
Preface 1
Introduction to recombinant DNA
J. Scott 3
Human biochemical genetics of enzyme proteins in the new age of molecular genetics
D. M. Swallow and D. A. Hopkinson 17
Direct DNA analysis in family studies
S. Malcolm 32
Application and limitations of direct DNA analysis in genetic prediction
M. E. Pembrey 38
DNA analysis for ornithine transcarbamylase deficiency
R. Rozen, J. E. Fox, A. M. Hack, W.A. Fenton, A. L. Horwich and L. E. Rosenberg 49
Molecular genetics of PKU
F. Guttier and S. L. C. Woo 58
Human DNA repair defects
C.RA~ @
Molecular basis of at-antitrypsin deficiency and its potential therapy by gene transfer
F. D. Led1ey and S. L. C. Woo 85
Direct alteration of a gene in the human genome
O. Smithies 92
Diabetes mellitus, atherosclerosis, and the 5' flanking polymorphism of the human
insulin gene
T. Mandrup-Poulsen, D. Owerbach, J. Nerup, K. Johansen and A. Tybjcerg Hansen 98
Workshop on Screening for Congenital Adrenal Hyperplasia (steroid 21-hydroxylase
deficiency)
Introduction
G. M. Addison 111
Clinical aspects of congenital adrenal hyperplasia: early diagnosis and prognosis
1. A. Hughes 115
Biochemical aspects of congenital adrenal hyperplasia
J. Honour 124
Large-Scale Pilot Studies
Review of CAH screening programmes and the Scottish experience
A. M. Wallace 135
Neonatal screening programme for congenital adrenal hyperplasia in a homogenous
Caucasian population
E. Cacciari, A. Balsamo, A. Cassio, S. Piazzi, F. Bernardi, S. Salardi, A. Cicognani,
P. Pirazzoli, R. Zappulla, M. Capelli, M. Paolini and C. 1. Cordaro 142
Neonatal screening for congenital adrenal hyperplasia: a pilot study in France
J. L. Dhondt, C. Dorche, J. P. Farriaux and C. Courte 147
Existing CIinieal Diagnoses
Congenital adrenal hyperplasia in Birmingham: a retrospective analysis (1958-1985)
N. K. Virdi and A. Green 152
Prevalence of adrenal 21-hydroxylase deficiency in neonates born in the West Midlands:
a retrospective study
B. T. Rudd 155
v
vi
Clinical Symposium - Phenylketonuria
Introduction and explanation
J. T. Ireland 157
Maternal phenylketonuria
R. Koch, E. Gross Friedman, E. Wenz, K. Jew, C. Crowley and G. Donnell 159
Dietary problems of phenylketonuria: effect on CNS transmitters and their possible
role in behaviour and neuropsychological function
F. GuttIer and H. Lou 169
Diagnosis in relationship to treatment of hyperphenylalaninaemia
M. E. Blaskovics 178
Problems related to diet management of maternal phenylketonuria
P. B. Acosta and S. Stepnick-Gropper 183
Short Communications
Preface and Free Communications 203
Molecular biology of phenylalanine hydroxylase
R. Cotton, H. H. M. Dahl, J. F. B. Mercer, 1. Jennings, E. A. Haan, C. W. Chow,
D. M. Danks and F. J. Morgan 206
Hepatic phenylalanine hydroxylase and dietary tolerance in hyperphenylalaninaemic
patients
C. Largilliere, J. L. Dhondt and J. P. Farriaux 209
Phenylalanine metabolites in treated phenylketonuric children
K. Michals, M. Lopus, P. Gashkoff and R. Matalon 212
Magnesium-deficient rickets in a phenylketonuric patient on dietary treatment
A. Rottoli, E. Riva, G. Zecchini, F. Magno, A. Fiocchi, R. Longhi and M. Giovannini 215
Termination of strict diet in phenylketonuria: neurophysiological, psychological and
biochemical studies
A. W. Behbehani, M. Vollrath, 1. Matschke and U. Langenbeck 218
Effects of stopping phenylalanine-restricted diet on intellectual progress of children with
phenylketonuria
R. Cerone, S. Scalisi, M. C. Schiaffino and C. Romano 223
Maternal hyperphenylalaninaemia: dietary treatment during pregnancy
C. Romano, R. Cerone, C. Borrone, S. Scalisi, U. Caruso and S. Gatti 225
Maternal hyperphenylalaninaemia in Israel
B. E. Cohen, A. Szeinberg, Y. Zarjin, M. Normand, 1. Peled, Y. Blonder, A. Elitzur,
R, Hadar and S. Mashiach 227
Maternal phenylketonuria with increased tyrosine supplements
o. Sheil, N. Duignan, 1. P. Saul and E. R. Naughten 231
Screening for phenylketonuria in Yugoslavia (SR Croatia) 1979-1984
D. Mardesic, G. Gjuric, J. Jancikovic, P. GraniC and A. Stavljenic 234
Incidence of phenylketonuria and hyperphenylalaninaemia in a sample of the Turkish
newbgm population
1. Ozalp, T. Co§kun, M. Ceyhan, S. Tokol, O. Oran, G. Erdem, G. Tekinalp,
Z. DurmU§ and Y. Tarikahya 237
Atypical phenylketonuria with mild mental retardation caused by tetrahydrobiopterin
deficiency in a Chinese family
K.-J. Hsiao, P.-c. Chiu, W.-H. Cheng and S.-L. Chao 240
Dihydropteridine reductase deficiency: clinical, biochemical and therapeutic aspects
R. Cerone, S. Scalisi, M. Cotellessa, M. C. Schiaffino, U. Caruso and C. Romano 244
Partial dihydropteridine reductase deficiency and mental retardation
A. Sahota, R. J. Leeming, J. A. Blair, R. A. Armstrong, A. Green and B. E. Cohen 247
vii
Urine amino acid analysis by HPLC in the investigation of inborn errors of metabolism
J. M. Leah, T. Palmer, M. Griffin, C. J. Wingad, A. Briddon and V. G. Oberholzer 250
Plasma amino acid patterns in critically ill children
A. Briddon and V. G. Oberholzer 254
Treatment of hereditary tyrosinaemia (fumarylacetoacetase deficiency) by enzyme
substitution
B. Lindblad, J. Friden, J. Greter, E. Holme, S. Lindstedt and C. SiOsteen 257
Presentation of the data of the Italian registry for oculocutaneous tyrosinaemia
A. Fois, P. Borgogni, M. Cioni, M. Molinelli, R. Frezzotti, A. M. Bardelli,
G. Lasorella, L. Barberi, P. Durand, M. Vi Rocco, C. Romano, R. Parini, C.
Corbetta, M. Giovannini, E. Riva, N. Balato, R. Sartorio, F. Mollica, E. Zammarchi
and M. L. Battini 262
A new case of hyperlysinaemia with saccharopinuria
C. Vianey-Liaud, M. O. Rolland, P. Divry, G. Puthet, M. T. Zabot and J. Cotte 265
Failure of early diazepam treatment in a neonate with non-ketotic hyperglycinaemia
A. Aukett, R. A. Braithwaite and A. Green 268
Gyrate atrophy of the choroid and retina: 3 cases in one Italian family
A. Fois, P. Borgogni, M. Cioni, G. M. S. Mancini, M. Molinelli, M. Pizzetti, A. M.
Bardelli, L. Biagini, L. Barberi, C. Malpassi, E. Harms and W. J. Kleijer 272
Methylenetetrahydrofolate reductase and methy~tetrahydrofolate methyltransferase in
human fetal tissues and chorionic villi
Y. S. Shin, G. Pilz and W. Endres 275
Kinetic studies on the glucose-6-phosphate transport system in rat hepatic microsomal
membrane
Y. Igarashi, S. Kato and K. Tada 277
Long term cornstarch therapy in glycogen storage disease types I, Ib and III
R. Gatti, G. Lamedica, M. Vi Rocco, D. Massocco, N. Marchese and C. Bo.rrone 280
Galactose-l-phosphate-uridyl transferase activity in chorionic villi: a first trimester
prenatal diagnosis of galactosaemia
M. O. Rolland, G. Mandon, J. P. Farriaux and C. Dorche 284
Molecular heterogeneity of McArdle disease
D. Daegelen, S. Gautron, F. Mennecier, J.-c. Dreyfus and A. Kahn 287
Decreased affinity of phosphorylase a for glucose-I-phosphate in polymorphonuclear
leukocytes of patients with glycogenosis type VI
D. Pieniazek and E. Pronicka 291
The diagnosis and treatment of a patient with medium-chain acyl-CoA dehydrogenase
deficiency: overnight fasting does not result in the expected urinary metabolite profile
A. H. van Gennip, H. D. Bakker, M. Duran and L. J. van Oudheusden 293
A new case of familiar Co-C dicarboxylic aciduria with favourable evolution
14
E. Riudor, A. Ribes, M. Boronat, C. Sabado, C. Dominguez and A. Ballabriga 297
Pyruvate carboxylase responsive to ketosis in a multiple carboxylase deficiency patient
A. Velazquez, D. von Raesfeld, A. Gonzalez-Noriega, L. Gonzalez, C. Garay,
R. Ortiz and V. del Castillo 300
Neonatal screening for biotinidase deficiency: an update
B. Wolf, G. S. Heard, L. G. Jefferson, K. A. Weissbecker, J. R. Secor McVoy, W. E.
Nance, P. L. Mitchell, F. W. Lambert and A. S. Linyear . 303
GM gangliosidosis with hexosaminidase A and B defect: report ofa family with motor
2
neuron disease-like phenotype
A. Federico, G. Ciacci, I. d'Amore, R. Pallini, S. Palmeri, A. Rossi, N. Rizzuto and
G. C. Guazzi 307
viii
A comparison between hepatocytes and macrophages of sphingomyelin, cholesterol and
acid lipase in various types of Niemann-Pick disease
A. Lageron 311
Juvenile dystonia without vertical gaze paralysis: Niemann-Pick type C disease
A. Federico, S. Palmeri, O. Van Diggelen, E. Ferrari and G. C. Guazzi 314
Pre- and postnatal diagnosis of the cerebro-hepato-renal (Zellweger) syndrome via a
simple method directly demonstrating the presence or absence of peroxisomes in
cultured skin fibroblasts, amniocytes or chorionic villi fibroblasts
R.I. A. Wanders, G. Schrakamp, H. van den Bosch, 1. M. Tager, H. W. Moser,
A. E. Moser, P. Aubourg, W.l. Kleijer and R. B. H. Schutgens 317
Impaired cholesterol side chain cleavage activity in liver from patients with cerebro
hepato-renal (Zellweger) syndrome in relation to the accumulation of di- and
trihydroxycoprostanoic acid in serum
R.I. A. Wanders, H. S. A. Heymans, R. B. H. Schutgens, 1. van Eldere and H. 1.
Eyssen 321
Deficiency of dihydroxyacetonephosphate acyltransferase and catalase-containing
particles in patients with infantile Refsum's disease
R.I. A. Wanders, R. B. H. Schutg ens, G. Schrakamp, H. van den Bosch, 1. M. Tager,
B. T. Poll-The and 1. M. Saudubray 325
Peroxisomal abnormalities in rhizomelic chondrodysplasia punctata
H. S. A. Heymans, 1. W. E. Oorthuys, G. Nelck, R.I. A. Wanders, K. P. Dingemans
and R. B. H. Schutgens 329
Cytogenetic studies of three families with ataxia-telangiectasia (Louis-Bar syndrome)
L. Chessa, A. Federico, S. Raimondi, G. C. Guazzi and E. Gandini 332
Author Index
Acosta, P. B. 183 Di Rocco, M. 262, 280 Hsiao, K.-J. 240
Addison, G. M. 111 van Diggelen, O. 314 Hughes, I. A. 115
d'Amore, I. 307 Dingemans, K. P. 329 Igarashi, Y. 277
Arlett, C. R. 69 Divry, P. 265 Ireland, J. T. 157
Armstrong, R. A. 247 Domingez, C. 297 JanCikovic, J. 234
Aubourg, P. 317 Donnell, G. 159 Jefferson, L. G. 303
Aukett, A. 268 Dorche, C. 147, 284 Jennings, I. 206
Bakker, H. D. 293 Dreyfus, J.-C. 287 Jew, K. 159
Balato, N. 262 Duigan, N. 231 Johansen, K. 287
Ballabriga, A. 297 Duran, M. 293 Kahn, A. 287
Balsamo, A. 142 Durand, P. 262 Kato, S. 277
Barberi, L. 262, 272 Durmu§, Z. 237 Kleijer, W. J. 272, 317
Bardelli, A. M. 262, 272 van Eldere, J. 321 Koch, R. 159
Battini, M. L. 262 Elitzur, A. 227 Lageron, A. 311
Behbehani, A. W. 218 Endres, W. 275 Lambert, F. W. 303
Bernardi, F. 142 Erdem, G. 237 Lamedica, G. 280
Biagini, L. 272 Eyssen, H. J. 321 Langenbeck, U. 218
Blair, J. A. 247 Farriaux, J. P. 147,209,284 Largilliere, C. 209
Blaskovics, M. E. 178 Federico, A. 307,314, 332 Lasorella, G. 262
Blonder, Y. 227 Fenton, W. A. 49 Leah, J. M. 250
Borgogni, P. 262,272 Ferrari, E. 314 Ledley, F. 85
Boronat, M. 297 Fiocchi, A. 215 Leeming, R. J. 247
Borrone, C. 225, 280 Fois, A. 262, 272 Lindblad, B. 257
van den Bosch, H. 317,325 Fox, J. E. 49 Lindstedt, S. 257
Braithwaite, R. A. 268 Frezzotti, R. 262 Linyear, A. S. 303
Briddon, A. 250, 254 Friden, J. 257 Longhi, R. 215
Cacciari, E. 142 Gandini, E. 332 Lopus, M. 212
Capelli, M. 142 Garay, C. 300 Lou, H. 169
Caruso, U. 225, 244 Gashkoff, P. 212 Magno, F. 215
Cassio, A. 142 Gatti, R. 280 Malcolm, S. 32
del Castillo, V. 300 Gatti, S. 225 Malpassi, C. 272
Cerone, R. 223,225,244 Gautron, S. 287 Mancini, G. M. S. 272
Ceyhan, M. 237 van Gennip, A. H. 293 Mandon, G. 284
Chao, S.-L. 240 Giovannini, M. 215, 262 Mandrup-Poulsen, T. 98
Cheng, W.-H. 240 Gjuric, G. 234 Marchese, N. 280
Chessa, L. 332 Gonzalez, L. 300 Mardesic, D. 234
Chiu, P.-C. 240 Gonzalez-Noriega, A. 300 Masiach, S. 227
Chow, C. W. 206 Granic, P. 234 Massocco, D. 280
Ciacci, G. 307 Green, A. 152, 247, 268 Matalon, R. 212
Cicognani, A. 142 Greter, J. 257 Matschke, I. 218
Cioni, M. 262,272 Griffin, M. 250 Mennecier, F. 287
Cohen, B. E. 227, 247 Gross Friedman, E. 159 Mercer, J. F. B. 206
Corbetta, C. 262 Guazzi, G. C. 307,314,332 Michals, K. 212
Cordaro, C. I. 142 GuttIer, F. 58, 169 Mitchell, P. L. 303
Co§kun, T. 237 Haan, E. A. 206 Molinelli, M. 262, 272
Cotellessa, M. 244 Hack, A. M. 49 Mollica, F. J. 206
Cotte, J. 265 Hadar, R. 227 Morgan, F. J. 206
Cotton, R. 206 Harms, E. 272 Moser, A. E. 317
Courte, C. 147 Heard, G. S. 303 Moser, H. W. 317
Crowley, C. 159 Heymans, H. S. A. 321,329 Nance, W. E. 303
Daegelen, D. 287 Holme, E. 257 Naughten, E. R. 231
Dahl, H. M. W. 206 Honour, J. 124 Nelck, G. 329
Danks, D. M. 206 Hopkinson, D. A. 17 Nerup, J. 98
Dhondt, J. L. 147,209 Horwich, A. L. 49 Normand, M. 227
ix:
x
Oberholzer, V. G. 250 Rizzuto, N. 307 Stepnick-Gropper, S. 183
Oorthuys, J. W. E. 329 Rolland, M. O. 265, 284 Swallow, D. M. 17
Oran, O. 237 Romano, C. 223, 225, 244, Szeinberg, A. 227
Ortiz, R. 300 262 Tada, K. 227
van Oudheusden, L. J. 293 Rosenberg, L. E. 49 Tager, J. M. 317, 325
Owerbach, D. 98 Rossi, A. 307 Tariahaya, Y. 237
Ozalp, I. 237 Rottoli, A. 215 Tekinalp, G. 237
Pallini, R. 307 Rozen, R. 49 Tokol, S. 237
Palmer, T. 250 Rudd, B. T. 155 Tybjrerg Hansen, A. 98
Palmeri, S. 307, 314 Sabado, C. 297 Velazquez, A. 300
Paolini, M. 142 Sahota, A. 247 Viney-Liaud, C. 265
Parini, R. 262 Salardi, S. 142 Virdi, N. K. 152
Peled, I. 227 Sartorio, R. 262 Vollrath, M. 218
Pembrey, M. E. 38 Saudubray, J. M. 325 Wallace, A. M. 135
Piazzi, S. 142 Saul, I. P. 231 Wanders, R. J. A. 317,
Pieni~ek, D. 291 Scalisi, S. 223, 225, 244 321, 325, 329
Pilz, G. 275 Schiaffino, M. C. 223, 244 Weissbecker, K. A. 303
Pirazzoli, P. 142 Schrakamp, G. 317, 325 Wenz, E. 159
Pizzetti, M. 272 Schutgens, R. B. H. 317, Wingad, E. J. 250
Poll-The, B. T. 325 321,325,329 Wolf, B. 303
Pronicka, E. 291 Scott, J. J. 3 Woo, S. L. C. 58, 85
Puthet, G. 265 Secor McVoy, J. R. 303 Zabot, M. T. 265
von Raesfeld, D. 300 Sheil, O .. 231 Zammarchi, E. 262
Raimondi, S. 332 Shin, Y. S. 275 Zappulla, F. 142
Ribes, A. 297 Siosteen, C. 257 Zarfin, Y. 227
Riudor, E. 297 Smithies, O. 92 Zecchini, G. 215
Riva, E. 215, 262 Stavljenic, A. 234
Title Index
Applications and limitations of direct DNA analysis 38
Atypical phenylketonuria with mild mental retardation caused by tetrahydrobiopterin deficiency in a
Chinese family 240
Biochemical aspects of congenital adrenal hyperplasia 124
Clinical aspects of congenital adrenal hyperplasia: early diagnosis and prognosis 115
A comparison between hepatocytes and macrophages of sphingomyelin, cholesterol and acid lipase in
various types of Niemann-Pick disease 311
Congenital adrenal hyperplasia in Birmingham: a retrospective analysis (1958-1985) 152
Cytogenetic studies of three families with ataxia-telangiectasia (Louis-Bar syndrome) 332
Decreased affinity of phosphorylase a for glucose-I-phosphate in polymorphonuclear leukocytes of
patients with glycogenosis type VI 291
Deficiency of dihydroxyacetonephosphate acyltransferase and catalase-containing particles in patients
with infantile Refsum's disease 325
Diabetes mellitus atherosclerosis, and the 5' flanking polymorphism of the human insulin gene 98
The diagnosis and treatment of a patient with medium-chain acyl-CoA dehydrogenase deficiency:
overnight fasting does not result in the expected urinary metabolite profile 293
Diagnosis in relationship to treatment of hyperphenylalaninaemia 178
Dietary problems of phenylketonuria: effect on CNS transmitters and their possible role in behaviour
and neuropsychological function 169
Dihydropteridine reductase deficiency: clinical, biochemcial and therapeutic aspects 244
Direct alteration of a gene in the human genome 92
Direct DNA analysis in family studies 32
DNA analysis for ornithine transcarbamylase deficiency 49
Effects of stopping phenylalanine-restricted diet on intellectual progress of children with
phenylketonuria 223
Failure of early diazepam treatment in a neonate with non-ketotic hyperglycinaemia 268
Galactose-l-phosphate-uridyl transferase activity in chorionic villi: first trimester prenatal diagnosis of
galactosaemia 284
GMl gangliosidosis with hexosaminidase A and B defect: report of a family with motor neuron disease-
like phenotype 307
Gyrate atrophy of the choroid and retina: 3 casel! in one Italian family 272
Hepatic phenylalanine hydroxylase and dietary tolerance in hyperphenylalaninaemic patients 209
Human biochemical genetics of enzyme proteins in the new age of molecular genetics 17
Human DNA repair defects 69
Impaired cholesterol side chain cleavage activity in liver from patients with cerebro-hepato-renal
(Zellweger) syndrome in relation to the accumulation of di- and trihydroxycoprostanoic acid in
serum 321
Incidence of phenylketonuria and hyperphenylalaninaemia in a sample of the Turkish newborn
population 237
Introduction to recombinant DNA 3
Juvenile dystonia without vertical gaze paralysis: Niemann-Pick type C disease 314
Kinetic studies on the glucose-6-phosphate transport system in rat hepatic microsomal membrane 227
Long-term cornstarch therapy in glycogen storage disease types I, Ib and III 280
Magnesium-deficient rickets in a phenylketonuric patient on dietary treatment 215
Maternal hyperphenylalaninaemia in Israel 227
Maternal hyperphenylalaninaemia: dietary treatment during pregnancy 225
Maternal phenylketonuria 159
Maternal phenylketonuria with increased tyrosine supplements 231
Methylenetetrahydrofolate reductase and methyltetrahydrofolate methyltransferase in human fetal
tissues and chorionic villi 275
Molecular basis of al-antitrypsin deficiency and its potential therapy by gene transfer 85
Molecular biology of phenylalanine hydroxylase 206
Molecular genetics of PKU 58
Molecular heterogeneity of McArdle disease 287
xi