Develop. Med. Child Neurol. 8, 1966, 31-44

Mental Subnormality in Hunter-Hurler Syndrome (Gargoylism):

A Suggested Biochemical Cause Gilbert F. Young* Hubert J . Wolf.1 John B. Blennerhassett:

PhiZip R. Dodge§

Introduction MENTAL subnormality is one of the cardinal features of Hunter-Hurler syn- drome (gargoylism). However, a few cases with average or above average intelligence have been reported (McKusick 1960). The purpose of this communication is to describe the clinical features and post- mortem findings in a man with this syndrome who had normal intelligence throughout his lifetime and to discuss the relationship between the man’s mental state and the neuropathologic findings.

Tuthill (1934) described the neuro- pathologic findings in one of Hurler’s original cases. Significant abnormalities in the brain were: (1) ballooned ganglion cells which stained positively with fat stains, (2) thickened adventitia of blood- vessels in the brain parenchyma, (3) thickened dura and leptomeninges, and (4) hydrocephalus. The finding of inclusions of a lipid substance within neuron perikaryons

has been confirmed as the most significant neuropathologic abnormality by almost all neuropathologists who have reported on this disease (Ashby et al. 1937, Green 1948). Harvey (1942) noted that all the 4 cases examined before 1942 had shown intracytoplasmic inclusions of a lipid- containing substance.

Jervis (1950) summarized the 150 cases of gargoylism reported up to that time. About 10 of them were said to be of ‘normal intelligence’. In the one examined post-mortem no ballooned nerve cells were found, This was a man of 29 years reported by Strauss et al. (1947), who noted that frozen brain tissue stained with Scharlach R revealed varied amounts of orange-red, granular lipid in large ganglion cells of the basal ganglia, pons, medulla, cerebellum and cerebral cortex; the amount of lipid was said to be no greater than that found in several ‘control’ cases.

DeLange et al. (1944) reported on two

Departments of Pathology and Neurology and Psychiatry of the Harvard Medical School and the James Homer Wright Pathology Laboratories, Charles S. Kubik Laboratory for Neuropathology, and the Joseph P. Kennedy, Jr., Memorial Laboratories of the Massachusetts General Hospital.

* N.I.N.D.B. Fellow in Pediatric Neurology, 1960-1963. + Research Fellow in Pathology. $’ Resident in Pathology. 5 Neurologist and Pediatrician, Massachusetts General Hospital. Dr. Young is presently Assistant Professor of Neurology, Medical College of South Carolina, Charleston,

South Carolina.

37

brothers, one of whom was examined post-mortem. The older brother died at 19 years, He was mentally backward, but his brain showed no significant abnormality. The younger brother was deaf and his behaviour was often antisocial, but he was not mentally subnormal. Neither boy had corneal opacities.

Smith et al. (1952) described a 29-year- old woman with slight bilateral deafness and average intelligence; and also a 28- year-old man with no mental defect and no corneal opacities. At 14 years, the male patient was unco-operative, moody and subject to fits of anger. He would not allow a systematic psychological evaluation. At autopsy his brain weighed 1,500 g. and was normal except for healed encephalo- malacia in the central portion of the basal ganglia.

Five clinical cases (probably examples of gargoylism) with normal intelligence have been reported by Ruggles (1931), Helmholz and Harrington (1931), and Hubeny and Delano (1941). These included a 17-month- old girl and a 7-year-old American Negro boy. The boy reported by Meyer and Ockner (1939) had an IQ of 114 at 7 years, but some time later his IQ had fallen to 84.

The pathologic findings in 12 cases of gargoylism (7 complete autopsies, 1 in- complete autopsy, and 4 biopsied cases) were reviewed by Lindsay rt crl. (1948). Their Case 1 had an 10 of 1 17 a year before his death at 10 years; at autopsy his nervous system showed no ballooned nerve.cells, but the leptonieningcs and the adventitia of parenchymatous blood-vessels were thickened. Their Case 2 was a mentally defective girl who died at 74 years; her brain likewise showed no abnormality except increased fibrous tissue elements of the arachnoid and blood- vessel adventitia.

Case-report (MGH $95-45-23)

The patient was followed at the Massa-

DEVELOPMENTAL MEDICINE A N D

38

CHILD NEUROLOGY. 1966, 8

chusetts General Hospital from the age of 16 years until his death at 23. During this time he was admitted on 5 separate occasions. His first admission was for investigating his several years’ history of progressive loss of vision and recurrent headaches.

Personal History The patient was born after an uncom-

plicated pregnancy. His birth-weight was 7 lb. There was an incomplete cleft involving the soft palate, but no other abnormalities. His early development was normal. He began to walk alone at 15 months and developed speech in his second year. At 15-16 months, the parents noted a dorsal kyphosis. Radiographs revealed an abnormality of the first lumbar vertebral body, for which the patient wore a succession of body casts constantly from the age of 16 months to 30 months. He always walked with a wide-based and waddling gait. Intellectual development proceeded at an average pace ; but deformities of head, neck, trunk, and of upper and lower extremities developed progressively.

He had the usual diseases of childhood without serious complications. He had frequent and persistent upper respiratory tract infections which were not relieved by tonsillectomy and adenoidectorny at 6 years.

The patient was referred to this hospital at 16 years because of steadily diminishing vision and recurring headaches in the previous 4-5 years. The headaches recurred every 2-4 weeks; they were severe and often woke hiin a t night. Occasionally they were accompanied by nausea and vomiting. There were no other specific complaints.

Fcrmily History The father was healthy and athletic. The

inother was alleged to have schizophrenia, and she had been in hospital several times

GILBERT I:. YOUNG HUBERT J. WOLFE JOHN B. BLENNERHASSETT PHILIP R. DODGE

in the past 8 years. A paternal cousin, a dwarf with normal intelligence, died in early adulthood; no medical details could be obtained.

Exam inat ion The patient was obviously dwarfed, with

most of the characteristic features of gargoylism (see Table); however, he was in no distress and did not appear acutely ill. There was a loud, precordial, systolic cardiac murmur; but no signs of congestive heart failure. The genitalia were normal.

Both corneas were cloudy and thick. There were 2 or 3 diopters of papilledema, and both blind spots were moderately enlarged. Vision was poor in each eye, and the visual fields were generally con- stricted.

Investigations The radiographic abnormalities are

summarized in the Table. Alder (Reilly) bodies were seen in blood leucocytes. The electrocardiogram showed left veiitricular hypertrophy and right axis deviation. An EEG was normal. The spinal fluid pressure was 480 mm. of water, and its protein content was 230 mg. per 100 nil. A ventriculogram, using 50 ml. of air, revealed symmetrical enlargement of the lateral and third ventricles (Fig. 1).

Course oj ' Illness After the ventriculogram, a ventriculo-

atrial shunt was performed. Subsequently the patient's vision improved, his papille- dema subsided and his headaches dis- appeared.

Fig. 1. Vcntriculograni demonstrating ventricular enlargement. Note also the enlarged and distorted sella turcica.

The psychologist reported an IQ of 100, At 21 yean, a left inguinal hernia repair and noted that performance on the was accomplished without difficulty. A Stanford-Binet sub-tests was consistently year later a left hydrocele was excised. At average. The patient had an extensive fund that time, the patient had significant of general information, and his comprehen- cardio-pulmonary symptoms. He slept on i o n of social situations was good. 2 pillows at night, and had mild dyspnea

39

TA

BL

E

Cla

ssic

al F

eaN

res of

Hun

ter-

Hur

ler

Synd

rom

e C

ompa

red

with

Fi

ndin

gs i

n th

e Pr

esen

t C

ase

( Hu

nte

r-H

url

er

Syn

dro

me)

(

MrK

us

irk

19

60)

Soft

-tis

sue

full

ness

in

low

er c

erbi

cal

area

fro

m C

4

to t

hora

cic

inle

t.

thic

keni

ng o

f pe

riew

phag

eal

tiss

ue

SK

EL

ET

AL

DE

FE

CT

S

Dw

arfi

sm

Lar

ge,

abno

rmal

ly s

hape

d he

ad

: F

lat

brid

ge o

f no

se

. .

. .

. .

Mal

form

ed t

eeth

._

. .

..

Hyp

erte

lori

sm

. .

. .

. .

Enl

arge

d se

lla

turc

ica

. .

. .

Sho

rt n

eck

..

..

Kyp

hosi

s w

ith

gibb

us'

Wed

ge-s

hape

d ve

rteb

ral

body

: :

Fla

ring

of

low

er r

ib c

age

. . . .

Bro

ad c

lavi

cles

and

rib

s . .

. .

Rel

ativ

ely

fixe

d th

orax

T

hick

dia

phys

is o

f lo

ng b

ones

: :

Flex

ion

cont

ract

ures

lar

ge j

oint

s . .

Lim

itat

ion

of jo

int

mot

ion

. .

Bro

ad h

ands

. .

..

. .

Stu

bby

fing

ers

. .

. .

1

Mis

-sha

pen

phal

ange

s Fl

exio

n co

ntra

ctur

es f

inge

rs

PR

OT

UB

ER

AN

T A

BD

OM

EN

H

epat

omeg

aly

. . . .

Sp

leno

meg

aly

. .

. .

. .

Her

nias

. .

. .

. . D

iast

asis

of

rect

i . .

. .

CA

RD

IAC

AB

NO

RM

AL

ITIE

S

Car

diac

mur

mur

s . .

. .

C

onge

stiv

e he

art

fail

ure

. ,

OT

HE

R A

BN

OR

MA

LIT

IES

C

oars

e fa

cial

fea

ture

s . .

L

arge

ton

gue

._

. .

. .

Enl

arge

d ad

enoi

d ti

ssue

. .

Noi

sy r

espi

rati

on

Gro

oved

. ri

dged

ski

n' .

: 1

Hir

suti

sm

. .

. .

. .

Ald

er b

odie

s in

leu

cocy

tes

. .

Dea

fnes

s . .

. .

. .

Cor

neal

opa

city

. .

. .

Pap

ille

dem

a . .

. .

. .

Hyd

roce

phal

us

Men

tal

whn

orm

alit

y

Clin

ira1

Hei

ght:

142

cm

., be

low

3 %

H

ead

circ

umfe

renc

e: 5

5 cm

. Sl

ight

fla

tten

ing

of b

ridg

e of

noI

e S

tubb

y m

alal

igne

d te

eth

Sho

rt n

eck

KyD

hosi

s at

leve

l of

LI

Slig

ht f

lari

ng o

f lo

wer

rib

cag

e

Vita

l ca

paci

ty:

one-

thir

d no

rmal

Fl

exio

n an

d w

ntra

ctur

es o

f hi

ps,

knee

s an

d el

bow

s. L

imit

ed m

otio

n in

the

hip

s. k

nees

, sh

ould

ers,

elb

ows

and

wri

sts.

Han

ds b

road

an

d st

ubby

. Fl

exio

n-co

ntra

ctur

es o

f 4t

h an

d 5t

h fi

nger

s

Liv

er:

4 FB

bel

ow c

osta

l m

argi

n S

plee

n: 3

FB

belo

w c

osta

l m

argi

n L

eft

ingu

inal

her

nior

rhap

hy

Not

men

tion

ed

Syst

olic

mur

mur

s, d

iast

olic

rum

ble

Prog

ress

ive

hear

t fa

ilur

e de

spit

e th

erap

y 5

mon

ths

befo

re d

eath

L

VH

and

rig

ht a

xis

on

EC

G

Bro

ad.

thic

k to

ngue

T

& A

at

6 ye

ars

Noi

sy r

espi

rati

on a

ll l

ife

Thi

ck s

kin

over

upp

er l

imbs

L

anue

o' h

air

over

tru

nk

Ald

erlb

odie

s in

leu

wcy

tes

Mil

d de

afne

ss a

t 23

yr.

M

oder

atel

y se

vere

cor

neal

clo

udin

g

Tw

o d

iopt

ers

elev

atio

n of

opt

ic d

isc

CSF

pres

sure

480

mm

. w

ater

IQ

100

. Hig

h-sc

hool

gra

duat

e. E

xten

sive

gen

eral

No

men

tal

subn

orm

alit

y. E

EG

nor

mal

in

fom

at io

n.

X-r

a.,

Poor

ly d

evel

oped

fro

ntal

sin

uses

Abn

orm

al s

hape

and

spa

cing

of

teet

h

Wid

e in

tero

rbit

al s

pace

M

arke

d en

larg

emen

t of

sella

wit

hout

er

osio

n o

r po

rosi

ty o

f cl

inoi

dn

Cer

vica

l ve

rteb

rae

mis

-sha

pen

Lum

bar

\ert

ebra

l bo

dies

mis

-sha

pen.

ec

cent

ric

beak

of

LI

Cla

vicl

es a

nd r

ibs

broa

d H

umer

i sh

ort

and

dia

phys

is b

road

, hu

mer

al h

ead

defo

rmed

, ace

tabu

la

shal

low

. fe

mor

al h

eads

def

orm

ed

and

fla

tten

ed

Phal

ange

s ab

norm

ally

bro

ad

Liv

er a

nd s

plee

n en

larg

ed

Hea

rt m

arke

dly

enla

rged

at

age

25

year

s

Ven

tric

ulog

ram

sho

wed

sym

mei

ric-

al

ly.

mod

erat

ely

enla

rged

la

tera

l

Posr

mor

rern

Len

gth:

148

cm

. W

eigh

t: 1

00 I

b.

Hea

d re

lativ

ely

larg

e. c

ircu

mfe

renc

e 55

cm

.

Nos

e br

idge

fla

tten

ed,

sadd

le-s

hape

d

Tee

th s

tubb

b. w

ide-

spac

ed.

man

y m

alfo

rmed

Sell

a m

oder

atel

y en

larg

ed

hut

pitu

itar

y

Sho

rt n

eck

Str

ikin

g ac

ute

kyph

otic

ang

ular

ion

01

ioH

er

dors

al t

o u

pper

lum

bar

spin

e

Slig

ht f

lari

ng o

f lo

wer

rib

cag

e C

lavi

cles

and

rib

s br

oad

and

thic

k

Mar

ked

thic

keni

ng a

nd b

owin

g of

mid

port

ion

of f

orea

rms

Hum

eri

shor

t. M

arke

d re

duct

ion

of m

obil

ity

of a

ll jo

ints

H

ands

bro

ad.

fing

ers

stub

by

Par

tial

fle

xion

-con

trac

ture

s of

fin

gers

, el

bow

s,

knee

s an

d hi

ps

Abd

omen

not

pro

tube

rant

. L

iver

: 7-

10

cm.

bel

ow

co

sta!

m

argi

n.

Spl

een:

wei

ght

140

g.

No

her

niat

ion

with

not

ches

norm

al s

ized

wei

ght

1.02

0 g

.

Hea

rt:

wei

ght

325

g..

righ

t ve

ntri

cle 0.1 cm

., le

ft v

entr

icle

1.5

cm

. th

ick.

Col

umna

car

- ne

ae m

uch

thic

kene

d. A

ll c

usps

of

4 va

lves

ab

norm

al.

Aor

tic

and

mit

ral

valv

es

mos

t in

volv

ed

by

firm

w

hite

th

icke

ning

an

d

nodu

les

alon

g va

lve

mar

gins

con

tain

ing

smal

l fl

ecks

of

calc

ific

atio

n

Coa

rse

faci

al f

eatu

res

Mod

erat

ely

enla

rged

tong

ue p

rotr

uded

sli

ghtl

y

' Sur

gica

l tr

ache

otom

y w

ound

! C

orne

as s

trik

ingl

y cl

oudy

B

rain

: w

eigh

t 1,

600

g. P

last

ic c

athe

ter

in r

ight

la

tera

l ve

ntri

cle

lead

ing

thro

ugh

valv

e in

to

and

thir

d v

en

tde

s, w

ith

norm

al

~ su

peri

or

vena

ca

va.-

Dur

a an

d

lept

o-

aque

duct

and

fou

rth

vent

ricl

e m

enin

ges

thic

k. e

spec

iall

y ov

er l

ower

bra

in-

stem

and

upp

er c

ord.

Sli

ght e

nlar

gem

ent

of

late

ral

vent

ricl

es.

Thi

rd a

nd

four

th v

entr

icle

s an

d aq

uedu

ct n

orm

al

I

~~

FB

- fin

ger-

brea

dths

GILBERT I:. YOUNG HUBERT J . WOLFE JOHN B. BLENNERHASSEI'T I'HILIP R . 1)Ol)C;t.:

on exertion and easy fatigability. He showed no evidence of loss of mental function.

The patient died at 23 years because of progressive heart failure. During the final 2 days of his life he was desperately i l l with fever (up to 103" F.). carbon dioxide retention, and an elevated blood-urea nitrogen. He seemed slightly deaf. His position sense was slightly diminished in the fingers and toes, but perception and localization of touch were intact. Pain perception was questionably diminished over his severely edematous feet and legs. His tendon jerks were active, and there were Babinski signs on both sides.

Post-itlortern Studies (Autopsjn #26.669) The gross findings are outlined in the

Table. Histologic examination of the viscera revealed large numbers of vacuo- lated cells which are typical of gargoylism (Smith et al. 1952). When tissue was fixed in dioxane and never allowed to come in contact with water during processing, these cells were shown to be distended with large amounts of material which had the staining characteristics of an acid muco- polysaccharide. Details of the histologic and histochemical findings have been reported by Wolfe et al. (1964). There was also histologic evidence ofsevere pulmonary congestion and pneumonia.

Neuropathologic Study The bones of the calvarium were thick.

A plastic tube passed through a small surgical defect in the right parietal bone into the right lateral ventricle proximally, and i t was connected through a valve to the superior vena cava distally. The sella turcica was enlarged. but the pituitary gland was normal in size. The cranial dura was slightly thickened; the dural sinuses and cerebral vessels were normal.

The brain weighed 1.600 g. The lepto- meninges were thick and tough over the

41

brain-stem. Otherwise, the external sur- faces were normal. The lateral ventricles were symmetrically enlarged to about twice normal size but were otherwise normal. The proximal end of the plastic tube was covered with choroid plexus, and tissue had grown into the openings and occluded the I umen.

The cerebellum and brain-stem appeared normal when sectioned. The dura of the spinal cord was markedly thickened throughout its entire length. The lepto- meninges were thickened over the spinal cord, especially in the cervical region.

Representative blocks of tissue were taken for section from all the important cerebral structures and from 4 levels of the spinal cord. These were embedded in paraffin, sectioned, and stained with hematoxylin-eosin, cresyl violet, periodic acid Schiff, and for myelin sheaths (Heidenhain method). Frozen sections from other samples of brain and spinal cord were stained with Sudan black and scarlet red. and with silver to demonstrate axis cylinders (Cajal method).

The dura and arachnoid were thicker than normal because of an increase of collagenous tissue and fibroblasts. A few blood-vessels in the centrum serniovale were surrounded by a lacy network of connective tissue (Fig. 2). No ballooned nerve cells or cells containing abnormal amounts of sudanophilic lipid were found, but sections of the optic nerves and tracts and the dorsal, ventral and lateral funiculi of the cord looked slightly pale when stained for myelin (Fig. 3). This change was most marked in the fasciculus gracilis. In the lateral funiculi, the zone of myelin sheath loss appeared to be regional; and was not limited to a particular system of fibers. No abnormality was recognized in the spinal roots or ganglia.

Comment The symptoms, signs and laboratory

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1966, 8

Fig. 2. Stained section from centruni semiovale (hematorcylin-eosin). The perivascular space is enlargcd ai?d contains a lacy arrangement of connective tissue.

Fig. 3. Stained section froni two levels of spinal cord (ticidenhain method for myelin sheaths). Note the palc staining of portions of the dorsal, lateral and ventral fiiniculi.

data leave no doubt as to the diagnosis of gargoylism in this case. Histochemical studies by Wolfe et al. (1964) established that large amounts of acid mucopoly- saccharides were deposited in the viscera, meninges and perivascular spaces of the brain. But the abnormal glycolipid often found in the nervous system and other organs was not present. The white matter lesions in the spinal cord were unexpected, and their pathogenesis is unknown. We could find no reference to similar lesions in other cases.

Communicating hydrocephalus is a well-recognized feature of gargoylism (Russell 1949). It has in fact been present in every one of several cases we have examined post-mortem. In each instance the leptomeninges around the basal cis- terns have been thickened. Russell (1949) and others have postulated that the menin- geal thickening impedes the circulation of cerebro-spinal fluid, and that hydro- cephalus is the consequence. Our observa- tions support this hypothesis. The present patient clearly had hydrocephalus with symptoms and signs of increased intra- cranial pressure which were alleviated by the ventriculo-atriostomy. Apparently an adjustment in intracranial hydrodynamics occurred which kept the patient free from symptoms of increased intracranial pres- sure, even though the shunt became occluded by connective tissue. The time of onset of the hydrocephalus in this case is not known, but i t did not prevent our patient from achieving an average level of intelligence. Hydrocephalus is known to impair mental processes in some patients, but this is unlikely to be a major cause for the mental subnormality in gargoylism; it is much more reasonable to incriminate the underlying metabolic defect.

The mucopolysaccharide abnormality appears to be the essential metabolic defect in gargoylism, accounting for the major skeletal and visceral changes as well

42

GILBERT F. YOUNG HUBERT J . WOLFE JOHN B. RLENNERHASSETT PHILIP R . DODGE

as the meningeal and perivascular findings. the mucopolysaccharide defect is not The mental defect usually arises from a necessarily accompanied by the glycolipid fault in glycolipid metabolism which leads abnormality. When the glycolipid abnor- to neuronal storage. It seems clear from mality is absent, it is highly probable that the observations of Wolfe et al. (1964) that the patient will be of normal intelligence.

SUMMARY The clinical features and autopsy findings are reported in a man of 23 years with

gargoylism. Hydrocephalus was demonstrated by pneumography and successfully treated by a ventriculo-atrial shunt. Throughout his life span, the patient was of average intelligence; there was no evidence of dementia.

The leptomeninges were thickened, and the perivascular spaces within the brain were enlarged. No storage material was found in the nerve cells.

The clinical and pathological findings are discussed in relation to the basic metabolic abnormalities. We postulate that mental retardation in gargoylism is associated with neuronal storage of glycolipid within the brain. Normal intelligence is to be expected in those patients with gargoylism who do not have neuronal storage.

RESUME Les bases weuro-pathologiques de la sub-normalith mentale clam le gargojlisnie (sjmlrrome cic

Hunter- Hurler) Les auteurs exposent les caractiristiques cliniques et les rCsultats de I’autopsie d’un cas

de gargoylisme chez un homme fig6 de 23 ans. L’hydrocephalie a it6 mise en evidence par pneumographie et traitie avec succts au moyen d’une derivation atrio-ventriculaire. Pendant la dude de sa vie le patient Ctait d’une intelligence moyenne; il n’y avait aucun signe de dimence.

Les leptomininges etaient Cpaissies et les espaces perivasculaires I’intirieur du cerveau itaient agrandis, aucune substance de reserve n’a Cte dCcelee dans les cellules nerveuses.

Les donnees cliniques et pathologiques sont discutees en fonction des anomalies mCta- boliques basiques. Nous emettons le postulat suivant : le retard mental dans le gargoylisme est associe au depbt de glycolipide en reserve dans les neurones a I’intCrieur du cerveau. On peut s’attendre a trouver une intelligence normale chez les patients atteints de gargoylisme qui n’ont pas de dCp8t dam les neurones.

ZUSAM MENFASSUNG Die neuropnthologische Basis der geistigen Zuruckgebliebenheit hei Car~oyl i smio (Hunter-

Hurler Syndrom) Es wird Bericht erstattet uber die klinischen Merkmale und Autopsiebefunde bei einem

23 jahrigen, mit Gargoylismus behafteten Mann. Wasserkopf wurde duch Pneumographie bewiesen und erfolgreich behandelt niit einer ventriculo-atrialen Seitenanknupfung. Der Patient war durchweg in seiner Lebensspanne von durchnittlicher Intelligenz, es lag kein Beweis von Demenz vor.

Die weichen Spinnwebehiute (Leptominges) waren verdickt und die perivaskuliiren Zwischenraume innerhalb des Gehirns waren vergrossert. Es wurde kein aufgespeichertes Material in den Nervenzellen gefunden.

Die klinischen und pathologischen Befunde in Beziehung zu den grundlegenden meta- bolischen Abnormalitaten werden besprochen. Wir setzen als gegeben voraus, dass geistige

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DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1966, 8

Zuriickgebliebenheit bei Gargoylismus mit neuronaler Speicherung von Glycolipid im Gehirn verbunden ist. Es wird normal eIntelligenz von diesen, mit Gargoylismus behafteten Patienten erwartet, die keine neuronale Speicherung haben.

RESUMEN La subnormalidad mental en el sindrome de Hurler (lipocondrodistroja). Una causa

bioquimica sugerida. Se describen el cuadro clinico y 10s resultados de una autopsia en el caso de un hombre

de 23 aiios que padecia del sindrome de Hurler. Se hallo hidrocefalia por medio de una neumografia, la cual fue tratada con buen Cxito por una derivacih ventriculo-auricular. Durante su vida entera, el paciente era de inteligencia media; y no habian ningunas pruebas de demencia.

Las leptomeninges se habian espesado y 10s espacios perivasculares dentro del cCrebro se habian engrandecido. No se encontr6 ninguna materia acumulada en las cClulas nerviosas.

Se discuten 10s descubrimientos clinicos y patologicos con relacion a las anormalidades metabblicas fundamentales. Sugerimos que un atraso mental en la enfermedad de Hurler se asocia con una ammulacion neuronal de glicolipina dentro del cbebro. Hay que esperar que se hallara una inteligencia normal en 10s pacientes que padecen de la enfermedad de Hurler y que no tienen acumulaciones neuronales.

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DeLange, C., Gerlings, P. G., DeKleyn, A., Lettinga, T. W. (1944) ‘Some remarks on gargoylism.’ Acta

Green, M. A. (1948) ‘Gargoylism (lipochondrodystrophy).’ J. Neuropath. exp. Neirrol., 7, 399. Harvey, R. M. (1942) ‘Hurler-Pfaundler syndrome (gargoylisrn).’ Amer. J. Roentgenol., 48,732. Helmholz, H. F., Harrington, E. R. (1931) ‘The syndrome characterized by congenital clouding of the cornea

Hubeny, M. J., Delano, P. J. (1941) ‘Dysostosis multiplex.’ Amer. J. Roenfgenol., 46, 336. Jervis, G . A. (1950) ‘Gargoylism (lipochondrodystrophy).’ Arch. Neurol. Psychiat., 63, 681. Lindsay, S., Reilly, W. A., Gotham, T. J., Skahen, R. (1948) ‘Gargoylism: 11. Study of the pathologic lesion

and clinical review of 12 cases.’ Amer. J. Dis. Child., 76, 239. McKusick, V. A. (1960) Heritable Disorders of Connective Tissue. St. Louis: Mosby, pp. 242-284. Meyer, S. J., Ockner, H. B. (1939) ‘Dysostosis multiplex with special reference to ocular findings.’ Amer. J

Ophrhal., 22, 713. Ruggles, H. E. (1931) ‘Dwarfism due to disordered epiphyseal development.’ Amer. J . Roenfgenol., 25, 91. Russell, D. S. (1949) Observations on the Pathology of Hydrocephalus. Spec. Rep. Ser. med. Res. Coim.

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adult cases with one autopsy.’ Ann. intern. Med., 36, 652. Straus, R., Merliss, R., Reiser, R. (1947) ‘Gargoylism. Review of literature and report of sixth autopsied

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