Table Of ContentCerebral Sphingolipidoses
A SYMPOSIUM ON TAY-SACHS' DISEASE
AND ALLIED DISORDERS
Edited by STANLEY M. ARONSON and BRUNO W. VOLK
Department of Pathology, State University of New York,
Downstate Medical Center
Isaac Albert Research Institute of the
Jewish Chronic Disease Hospital,
Brooklyn, New York
Conference Chairmen
STANLEY M. ARONSON
HEINRICH WAELSCH
WARREN M. SPERRY
BRUNO W. VOLK
1962
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CONTRIBUTORS AND PARTICIPANTS
IRMA ABRAMSON, Social Service Department, Jewish Chronic Disease Hos-
pital, Brooklyn, New York
JOSEPH L. ABRAMSON, Brooklyn Jewish Hospital; Jewish Chronic Disease
Hospital; Department of Neurology, State University of New York,
Downstate Medical Center, Brooklyn, New York
HARRY ALBAUM, Department of Biochemistry, Brooklyn College, Brooklyn,
New York
RICHARD J. ALLEN, Department of Pediatrics, University of Michigan Medi-
cal Center, Ann Arbor, Michigan
PAUL H. ALTROCCHI, National Heart Institute, National Institutes of Health,
Bethesda, Maryland
ALFRED A. ANGRIST, Department of Pathology, Albert Einstein College of
Medicine, Yeshiva University, Bronx, New York
HAROLD APPLETON, Department of Clinical Chemistry, New York Medical
College, New York, New York
STANLEY M. ARONSON, Department of Pathology, State University of New
York, Downstate Medical Center; Isaac Albert Research Institute of
the Jewish Chronic Disease Hospital, Brooklyn, New York
H. ASAO, Department of Neuropathology, New York State Psychiatric In-
stitute, New York, New York
H. W. BAIRD, III, Department of Pediatrics, Temple University School of
Medicine; St. Christopher's Hospital for Children, Philadelphia, Penn-
sylvania
BETTY Q. BANKER, Department of Pathology, Children's Hospital Medical
Center; Department of Neuropathology, Harvard Medical School, Bos-
ton, Massachusetts
ALEXANDER G. BEARN, The Rockefeller Institute, New York, New York
ELAINE R. BERMAN, Department of Biochemistry, Hebrew University, Ha-
dassah Medical School, Jerusalem, Israel
JOHN A. BIGLER, Children's Memorial Hospital; Department of Pediatrics,
Northwestern University Medical School, Chicago, Illinois
SAMUEL BOGOCH, Foundation for Research on the Nervous System,1 Boston,
Massachusetts
1 Formerly the Neurochemical Research Laboratory, Department of Psychiatry,
Harvard Medical School.
v
Vi CONTRIBUTORS AND PARTICIPANTS
GUNNAR BRANTE, Central Laboratory at the Central Hospital, Eskilstuna,
Sweden
ILONA BUBELIS, Department of Pathology, New York University, Bellevue
Medical Center of New York University, New York, New York
ERWIN CHARGAFF, Department of Biochemistry, Columbia University, Col-
lege of Physicians and Surgeons, New York, New York
H. S. COLEMAN, Department of Colloid Chemistry, Temple University,
School of Medicine, Philadelphia, Pennsylvania
ALLEN C. CROCKER, Department of Pathology, Children9s Hospital Medical
Center; Department of Pediatrics, Harvard Medical School, Boston,
Massachusetts
JOHN N. CUMINGS, Department of Chemical Pathology, Institute of Neurol-
ogy, The National Hospital, London, England
JOEL A. DAIN, Research Laboratories, Boston Dispensary; Department of
Biochemistry, Tufts University School of Medicine, Boston, Massachu-
setts
RUSSELL N. DEJONG, Department of Neurology, University of Michigan
Medical Center, Ann Arbor, Michigan
SAMUEL DUNKELL, Payne Whitney Psychiatric Institute, New York Hos-
pital, Cornell Medical Center, New York, New York
G. W. F. EDGAR, Institute for Epilepsy Research, Meer en Bosch, Heemstede,
Holland
SIDNEY FARBER, Children's Cancer Research Foundation, Children's Hos-
pital Medical Center; Harvard Medical School, Boston, Massachusetts
IRWIN FEIGIN, Department of Pathology, New York University School of
Medicine, New York, New York
Louis H. FINGERMAN, Research Laboratories of the Boston Dispensary,
Boston, Massachusetts
PATRICK J. FITZGERALD, Department of Pathology, State University of New
York, Downstate Medical Center; Kings County Hospital Center,
Brooklyn, New York
J. FOLCH-PI, Department of N euro chemistry, Harvard Medical School;
McLean Hospital, Waverly, Massachusetts
DONALD S. FREDRICKSON, National Heart Institute, National Institutes of
Health, Bethesda, Maryland
OWEN W. GARRIGAN, Department of Biochemistry, Columbia University,
College of Physicians and Surgeons, New York, New York
CONTRIBUTORS AND PARTICIPANTS vii
S. GATT, Department of Biochemistry, Hebrew University, Hadassah Medi-
cal School, Jerusalem, Israel
W. GIELEN, Institute for Physiological Chemistry, University of Cologne,
Cologne, Germany
MARTIN G. GOLDNER, Jewish Hospital of Brooklyn; Department of Medi-
cine, State University of New York, Downstate Medical Center, Brook-
lyn, New York
J. GONATAS, Department of Neurology, Albert Einstein College of Medicine,
Bronx, New York
HARRY GRAYZEL, Department of Pediatrics, Jewish Chronic Disease Hospital,
Brooklyn, New York
ALFRED F. HARRIS, Department of Biochemistry, Isaac Albert Research In-
stitute of the Jewish Chronic Disease Hospital, Brooklyn, New York
RUTH C. HARRIS, Department of Pediatrics, Columbia University, College of
Physicians and Surgeons; Babies Hospital, New York, New York
GORDON R. HENNIGAR, Department of Pathology, State University of New
York, Downstate Medical Center, Brooklyn, New York
H. HERMIDA, Brooklyn Veterans Administration Hospital, Brooklyn, New
York
L. P. HINTERBUCHNER, Department of Neurology, State University of New
York, Downstate Medical Center; Department of Neurology, Jewish
Chronic Disease Hospital, Brooklyn, New York
DAVID YI-YUNG HSIA, Department of Pediatrics, Northwestern University
Medical School; Children's Memorial Hospital, Chicago, Illinois
GEORGE A. JERVIS, Research Department, Letchworth Village Hospital,
Thiells, New York; Columbia University, College of Physicians and
Surgeons, New York, New York
ABRAM KANOF, Jewish Chronic Disease Hospital; Jewish Hospital; State
University of New York, Downstate Medical Center, Brooklyn, New
York
WILLIAM D. KAPLAN, Department of Genetics, City of Hope Medical
Center, Duarte, California
JOHN D. KARKAS, Department of Biochemistry, Columbia University, Col-
lege of Physicians and Surgeons, New York, New York
DAVID KERSHNER, Department of Surgery, Jewish Chronic Disease Hospital,
Brooklyn, New York
E. KLENK, Institute for Physiological Chemistry, University of Cologne,
Cologne, Germany
viii CONTRIBUTORS AND PARTICIPANTS
ALFRED G. KNUDSON, JR., Department of Pediatrics, City of Hope Medical
Center, Duarte, California
MARCUS D. KOGEL, Albert Einstein College of Medicine, Yeshiva Univer-
sity, Bronx, New York
SAUL R. KOREY, Department of Neurology, Albert Einstein College of Medi-
cine, Yeshiva University, Bronx, New York
BENJAMIN H. LANDING, Children's Hospital; University of Cincinnati, Col-
lege of Medicine, Cincinnati, Ohio
JONATHAN LANMAN, Department of Pediatrics, State University of New
York, Downstate Medical Center; Kings County Hospital Center,
Brooklyn, New York
SYDNEY S. LAZARUS, Department of Laboratories, Isaac Albert Research
Institute; Jewish Chronic Disease Hospital, Brooklyn, New York
MARJORIE B. LEES, McLean Hospital, Waverley; Harvard Medical School,
Boston, Massachusetts
RICHARD R. MASLAND, National Institute of Neurological Diseases and
Blindness, Bethesda, Maryland
JOHN H. MENKES, Department of Pediatrics; Johns Hopkins University,
School of Medicine, Baltimore, Maryland
JAMES Q. MILLER, Department of Pathology, Children's Hospital Medical
Center; Department of Neuropathology, Harvard Medical School, Bos-
ton, Massachusetts
ROBERT A. MOORE, State University of New York, Downstate Medical
Center, Brooklyn, New York
HUGO MOSER, Department of Neurology, Harvard Medical School, Boston,
Massachusetts
EDWARD MUNTWYLER, Department of Biochemistry, State University of
New York, Downstate Medical Center, Brooklyn, New York
NTINOS C. MYRIANTHOPOULOS, National Institute of Neurological Diseases
and Blindness, Bethesda, Maryland
JEAN S. NAYLOR, Department of Pediatrics, Northwestern University Medi-
cal School; Children's Memorial Hospital, Chicago, Illinois
HARUO OKAZAKI, Department of Pathology, State University of New York,
Downstate Medical Center, Brooklyn, New York
G. PADBERG, Institute for Physiological Chemistry, University of Cologne,
Cologne, Germany
JOSEPH B. PINCUS, Department of Pediatrics, Jewish Hospital of Brooklyn,
Brooklyn, New York
CONTRIBUTORS AND PARTICIPANTS ix
JAMES O. PINKSTON, Department of Physiology, State University of New
York, Downstate Medical Center, Brooklyn, New York
CHARLES M. POSER, Department of Medicine (Neurology), University of
Kansas, School of Medicine, Kansas City, Kansas
ABRAHAM M. RABINER, Jewish Chronic Disease Hospital; Department of
Neurology, State University of New York, Downstate Medical Center,
Brooklyn, New York
LEON ROIZIN, New York State Psychiatric Institute; Department of Neuro-
pathology, Columbia University, College of Physicians and Surgeons;
Brooklyn Veterans Administration Hospital, New York, New York
ABRAHAM ROSENBERG, Department of Biochemistry, Columbia University,
College of Physicians and Surgeons, New York, New York
GEORGE L. ROUSER, Department of Biochemistry, City of Hope Medical
Center, Duarte, California
JACK H. RUBINSTEIN, Hamilton County Diagnostic Clinic for the Mentally
Retarded; University of Cincinnati, College of Medicine, Cincinnati,
Ohio
ABRAHAM SAIFER, Department of Biochemistry, Isaac Albert Research In-
stitute of the Jewish Chronic Disease Hospital, Brooklyn, New York
STANLEY SAMUELS, Department of Neurology, Albert Einstein College of
Medicine, Yeshiva University, Bronx, New York
GERHARD SCHMIDT, Research Laboratories of the Boston Dispensary; De-
partment of Biochemistry, Tufts University, School of Medicine, Bos-
ton, Massachusetts
FRANZ SEITELBERGER, Neurologisches Institut der Universitdt Wien, Vienna,
Austria
KASPAR SIMMA, Department of Neurology and Psychiatry, Landes-Heil-
und Pflegeanstalt Valduna, Vorarlberg, Austria
WALTER SLADE, Department of Neurology, Brooklyn Veterans Administra-
tion Hospital; Department of Neurology, State University of New
York, Downstate Medical Center, Brooklyn, New York
ALBERT E. SOBEL, Department of Biochemistry, Jewish Hospital of Brook-
lyn, Brooklyn, New York
HARRY SOBOTKA, Department of Chemistry, The Mount Sinai Hospital,
New York, New York
WARREN M. SPERRY, Department of Biochemistry, Columbia University;
Department of Psychiatric Research, New York State Psychiatric Insti-
tute, New York, New York
X CONTRIBUTORS AND PARTICIPANTS
MONA SPIEGEL-ADOLF, Department of Colloid Chemistry, Temple Univer-
sity, School of Medicine, Philadelphia, Pennsylvania
E. G. SZEKELY, Department of Experimental Neurology, Temple Univer-
sity, School of Medicine, Philadelphia, Pennsylvania
ROBERT D. TERRY, Department of Pathology, Albert Einstein College of
Medicine, Yeshiva University, Bronx, New York
SIEGFRIED J. THANNHAUSER, Research Laboratories, Boston Dispensary ;
Department of Biochemistry, Tufts University School of Medicine, Bos-
ton, Massachusetts
WALLACE W. TOURTELLOTTE, Department of Neurology, University of
Michigan Medical Center, Ann Arbor, Michigan
L. LAHUT UZMAN, Department of Neurology, Harvard Medical School;
Boston City Hospital, Boston, Massachusetts
EDWARD VASTOLA, Department of Neurology, State University of New
York, Downstate Medical Center; Kings County Hospital Center,
Brooklyn, New York
BRUNO W. VOLK, Isaac Albert Research Institute of the Jewish Chronic
Disease Hospital; Department of Pathology, State University of New
York, Downstate Medical Center, Brooklyn, New York
SALOME G. WAELSCH, Department of Anatomy, Albert Einstein College of
Medicine, Yeshiva University, Bronx, New York
HEINRICH WAELSCH, Department of Biochemistry, Columbia University;
Department of Psychiatric Research, New York State Psychiatric In-
stitute, New York, New York
H. WEICKER, Research Laboratories, Boston Dispensary; Department of
Biochemistry, Tufts University, School of Medicine, Boston, Massa-
chusetts
HARRY WEINER, Department of Orthopedic Surgery, Jewish Chronic Disease
Hospital, Brooklyn, New York
MARTIN WEISS, Department of Pathology, Albert Einstein College of Med-
icine, Yeshiva University, Bronx, New York
ALEXANDER S. WIENER, Jewish Chronic Disease Hospital; New York Uni-
versity, College of Medicine; Office of the Chief Medical Examiner of
New York City, New York, New York
ABNER WOLF, Department of Pathology, Columbia University, College of
Physicians and Surgeons; Presbyterian Hospital, New York, New York
HARRY M. ZIMMERMAN, Department of Laboratories, Montefiore Hospital;
Department of Pathology, Columbia University, College of Physicians
and Surgeons, New York, New York
PREFACE
The Symposium on the Cerebral Sphingolipidoses was held at the Isaac
Albert Research Institute of the Jewish Chronic Disease Hospital and the
Downstate Medical Center of the State University of New York on March
29 and 30, 1961. It was sponsored by these institutions and the National
Tay-Sachs Association.
About half of the 90 participants came from the metropolitan area, the
others from domestic and foreign research institutions. The scope of the
papers presented and the interest shown in the Symposium demonstrate
the significance attached to an intensive study of Tay-Sachs' and allied
diseases. The reasons for this become apparent when one considers the con-
tributions to our basic knowledge of lipid chemistry, genetics, and neuro-
pathology which the study of these diseases has made in recent years.
These investigations provide common ground for biochemists, geneticists,
pathologists, and clinicians.
Partly because of the hereditary nature of Tay-Sachs' disease and other
sphingolipidoses, any new discovery in these diseases has general meaning
and permits cautious generalization far beyond its clinical significance. The
complexity of the brain lipids has presented the biochemist with a con-
tinuous challenge as to the development of adequate methods for their
analysis and characterization. This aspect became very apparent at the
Symposium where the applications and results of the most up-to-date proce-
dures, such as electron microscopy, chromatography, and histochemistry
were discussed. The results of such investigations will form the basis for an
attack on the enzymatic mechanisms and their abnormalities in the sphingo-
lipidoses. It is in the realm of this aspect of brain metabolism that the
deviation from normal may be expected to be found.
A unique feature of the Symposium was the constant awareness of the
clinical implications of the fundamental studies presented. This was due
not only to the participation of clinicians and presentation of papers by
them but also to the existence in the Jewish Chronic Disease Hospital of
the only clinical unit in the world devoted exclusively to Tay-Sachs' and
allied diseases. This clinical unit, and in particular the Isaac Albert Re-
search Institute, derive part of their support from the National Tay-Sachs
Association, the members of which are mainly parents of children afflicted
by these degenerative diseases of the nervous system. The enthusiasm and
active participation of the National Tay-Sachs Association is an impressive
example of the conversion of personal grief into a public service.
The Symposium was organized by Dr. Bruno W. Volk and Dr. Stanley
M. Aronson. The amount of thought and labor devoted to this effort was
xi
xii PREFACE
attested to by the excellence of the program and by the high level of the
discussion. The hospitality of the Institute and of the Downstate Medical
Center was gratefully acknowledged by all participants. They not only
greatly enjoyed the Symposium but in addition went back to their labora-
tories and clinics with a broader point of view as to the general significance
of their own fields of interest.
HEINRICH WAELSCH
New York, June, 1961
