SEITELBERGER’S
SPASTIC
AMAUROTIC
AXONAL
IDIOCY
Report
of
a Case
in
a 9-yearoId
Boy
with
Comment
on
Visceral
Manifestations
Hisayo
Nakai,
M.D.,
Benjamin
H. Landing,
M.D.,
and William K. Schubert, M.D.Divisions of Pathology and Pediatrics, Children’s Hospital and Children’s Hcspital Research Foundation, Cincinnati, and the University of Cincinnati College of Medicine
(Accepted September 3, 1959; submitted July 27.)
ADDRESS: (B.H.L.) Children’s Hospital, Elland and Bethesda Avenues, Cincinnati 29, Ohio.
PEDIATRICS, March 1960
441
S
PASTIC amaurotic axonal idiocy, asorigi-nally described by Seitelberger,1 and
later by Rabinowicz and Wildi,2 is a pro-gressive degenerative disorder of the
cen-tral nervous system. The first-described’
patients with this disorder were identical
twin sisters who died at the ages of 5 and 6 years with tile neurologic findings of
amaurosis, nystagmus, idiocy, spasticity
with contractions, and incontinence.
Seitel-berger and Gross’ have since briefly
dis-cussed a 3-year-old girl whose parents were
first cousins and have mentioned another
3-year-old girl with tile same disorder.
Rabinowicz and Wildi have reported on a
girl who died at age 11 years 11 months,
whose sister had died at the same age with
the same clinical picture. Their patient’s
disease began at 3 years with hyperreflexia
and unsteady gait. By age 5 years, she had
lost abilit’ to walk and talk, had bilateral
Babinski response, and showed increased hyperreflexia. By age 7 years, she was bed-ridden and spastic, by 10 years she was
cachectic, with incontinence and flexion
contractions, and at 11 years, she developed
pendulous nystagmus.
Pathologically, the condition is
charac-terized by localized swelling and
hyaliniza-tion of axons, and perhaps also of dendrites
and nerve cell bodies, associated with
de-myelination and gliosis, and deposition of
cilrOmOhpid pigment in astrocytes,
microg-ha and nerve cells. Seitelberger and Gross’
give the sites of involvement, in order of
severity, as: pallidum, zona rubra of
sub-stantia nigra, ansa lenticularis, ventral
thai-amic nuclei, cerebellum, red nucleus, and
dorsolateral portions of medulla and cervical spinal cord. Rabinowicz and Wildi,’ on the other hand, list the order of severity as: dorsolateral gray nuclei of brain stem, pul-vinar, nuclei of Goll and Burdach, dorsal roots of cervical cord, cerebral cortex, caim-date, putamen, anterior thalamus, and pal-lidum. These latter writers describe cerebel-lar involvement, but do not list its position
in the scale of severity of lesions.
Although none of the lesions of hyalmne swelling of axons, demyelmnation, gliosis, and chromolipid deposition can be consi-dered pathognomonic, their occurrence in combination, with repetitive patterns of distribution, appears to constitute a neuro-pathologic entity, for which the writers prefer to retain the name “spastic amauro-tic axonal idiocy of Seitelberger, “ rather than “juvenile Hallervorden-Spatz disease,” the term now perferred by Seitelberger. Despite the elements of pathologic resem-blance to classical Hallervorden-Spatz dis-ease of adults, it seems more probable that the disorder under discussion is a different condition with certain features of similarity,
than that they “. . . constitute a single
genetic unit and their differences arise only from the different point in time of their
on-set.”
The most important point of distinction between the disorders is the hemosiderosis of the basal nuclei present, by definition, in Hallervorden-Spatz disease. Although
Rabi-nowicz and Wildi’ described pallidal
sider-osis (by Gomori stain) in their patient with
spastic amaurotic axonal idiocy, they
442
content of the tissue was normal. As the chromolipid pigment gives a strong positive
ferricyanide reduction test,4 it is possible
that a reaction of this type was responsible
for a false-positive iron stain in their
ma-terial.
The reported occurrence of the disease
in sisters, and in the child of a
consanguine-ous marriage, suggests that the disorder is
genetically determined, and the family
his-tories presented by previous writers
mdi-cate that it is a recessive condition. The
fact that the first six reported patients were
girls has led to the suggestion that the trait
is sex-linked or sex-limited.’
The purpose of this paper is to describe
the occurrence of spastic amaurotic axonal
idiocy in a 9%-year-old boy, who also
suf-fered from transient hypoplastic anemia,
and terminally from severe electrolyte
im-balance. The presence of visceral chromo-lipid pigment, with histochemical similarity
to that in the central nervous system, is also
described, and certain possible diagnostic implications of this finding are discussed.
CASE
REPORT
History
KB. (CH #74863, birth date January 6, 1949) was the second child of a 40-year-old
father and a 38-year-old mother. He weighed
3.7 kg at birth. Family history, and the
prena-tal and postnatal periods were not abnormal.
At age 11 months he was admitted to another
hospital because of pallor of 3 months’
dura-tion; concentration of hemoglobin was 1.6 gm/
100 ml. Physical examination showed no
ab-normalities except pallor and irritability.
Leu-kocyte count was 8,800/mm’. Routine urine
studies and skeletal survey showed no
abnor-mal findings. He was not jaundiced (icterus
index 2.4), and erythrocyte fragility tests gave
normal values; bone marrow aspiration showed
marked reduction of erythrocyte precursors
and was diagnosed as consistent with chronic
hypoplastic anemia. With transfusions, the
he-moglobin level increased to 8 to 9 gm/100 ml;
administration of folic acid produced no re-ticulocyte response and further transfusions
raised the hemoglobin to 13 gm/100 ml. He
was discharged with no specific medication
prescribed.
Two months later he was readmitted for an
upper respiratory infection. Hemoglobin was
10.2 gm/100 ml and leukocyte count was
2,550/mm’ with 98% lymphocytes and 2%
neu-trophiles. Bone marrow aspiration showed an
erythroid/myeloid ratio of 3. With transfusion,
the hemoglobin rose to 15.2 gm/100 ml, and
he was discharged, to receive folic acid 10
mg/day and ferrous sulfate at home. After
an-other 2 months he was again admitted for transfusion, and there were four more
admis-sions for this purpose by the age of 20 months.
Admissions to Cincinnati Children’s Hospital
FIRST AND SECOND ADMISSIONS: He then
be-came a patient at this hospital, where he was
first admitted at age 21 months, weighing 13.4
kg. Developmental history showed that he had
sat at 6 months, walked at 15 months, and had
begun to talk at 18 months. Hemoglobin on
admission was 7.7 gm/100 ml, reticulocyte
count 0.6%, platelets 13,500/mm’, and leuko-cyte count was 4,000/mm’ with 68%
lympho-cytes, 24% neutrophiles, 6% eosinophils and 2%
monocytes. He was transfused, with an
in-crease in hemoglobin to 11 gm/100 ml. At 22 months, the hemoglobin was raised from 6 to 10.1 gm/100 ml by transfusions; 23 months later, the hemoglobin was 4.5 gm/100 ml. The weight was 13.9 kg and height was 81 cm. Two months later, however, the weight had decreased to 13.3 kg. During both these ad-missions he was transfused.
THIRD ADMISSION: He then did well for 4
months (age 23 years) when he was admitted because of fever for 1 week, poor fluid intake, and vomiting. Physical examination showed an
acutely ill listless child. Tendon reflexes were
symmetrical and normally active. Shortly after
admission he developed nuchal rigidity;
lum-bar puncture showed initial pressure of 160 mm H20, 300 leukocytes/mm3 (90% neutro-philes), sugar 47 mg/100 ml, chloride 109 meq/l, and protein 98 mg/100 ml. Because of
the possibility that he had partially treated
meningitis (he had received penicillin before
admission) he was given penicillin and
sulfa-diazine, with improvement in the clinical
pie-ture. At this time the hemoglobin was 13 gm/
100 ml, and he weighed 14.3 kg. He recovered with no apparent muscle weakness or other
neurologic sequelae, and did well, except for
failure to gain weight, for 18 months.
Physical examination showed no specific
find-ings. Chemical values in the blood were as
fol-lows: pH 7.3, carbon dioxide content 11.8
meq/l, chloride 93.5 meq/l, and nonprotein
nitrogen 4:3 mg. ‘100 ml. He was treated with
penicillin and fluids intravenously, and
re-covered rapidly.
FIFTH ADMISSION: He was next admitted at
age 82 ears because of easy fatigability
and “shaking” with voluntary motions. At this
time he weighed 17.7 kg and was 106.7 cm in
height. The head appeared large for the body,
and he had partial bilateral ptosis.
Fundu-scopic examination showed a peppery
distribu-tioii of pigment, with a tendency to a
streak-pattern in the periphery. The tendon reflexes
were absent, or weak with re-enforcement,
bi-laterally, amid his performance in the finger-to-nose and finger-to-finger tests was poor. He
had exaggerated postural rigidity, but no
cog-wheel or rebound motion of the arms or legs.
Sensation was apparently normal, and there
were no meningeal signs.
Hemoglobin was 12.5 gm/100 ml, and bone
marrow showed relative lvmphocytosis.
Con-centration of iron in serum was 63 g/100 ml
and serum copper was 92 mg/100 ml. Two
lumbar punctures gave normal cerebrospinal
fluid. Skull and skeletal roentgenograms were
normal except for retarded bone age.
Electro-encephalogram showed slow dysrhythmia with
nonfocal paroxysmal trends, consistent with
diffuse organic disease. After a tryptophan
loading test, the urine showed normal
amino-acid pattern, except for a low level of histidine
and a high level of alanine, and xanthurenic
acid excretion was not elevated. He was
dis-charged with no definite diagnosis, and no
specific treatment. His exercise tolerance
de-teriorated slowly, he became more shaky, and
also slow in motion.
SIXTH ADMISSION: He was readmitted at age
92 years. Physical examination was
essen-tially unchanged from the previous admission.
Chemical values in the blood included : pH
7.38; carbon dioxide content 15.7 meq/l;
chlo-ride 109.2 meq/l; blood urea nitrogen 21,
calcium 8.4, and phosphorus 5.8 mg/100 ml;
alkaline phosphatase 1.4 Bodansky units; glu-cose 72 mg/100 ml; total protein 8.2, albumin
4.7, globulin 3.5 gm/100 ml; total bilirubin
0.2 mg/100 ml; cephalin and thymol floccula-tions negative; thymol turbidity 5 units; zinc sulfate turbidity
7.5
units; total serum lipid835 mg/100 ml. Cerebrospinal fluid was
nega-tive on two examinations. Roentgenograms of
the skull were again normal, but electro-encephalogram showed more disorder than on the previous admission.
FINAL ADMISSION: Four months later his last
admission was precipitated by severe vomiting.
Physical examination showed pulse 80/mm,
respirations 34/mm of Kussmaul type, and
blood pressure of 140/110 mm Hg. Chemical
values in the blood were: PH 7.18; carbon dioxide content 5.6 meq/l; chloride 104.3 meq/l; blood urea nitrogen 21 mg/100 ml, sodium 141 meq/l; potassium 5.6 meq/l; cal-cium 8.8, glucose 90 mg/100 ml. Hemoglobin
was 14.3 gm/100 ml, and leukocyte count was 20,100/mm’ with 88% neutrophiles. Cerebro-spinal fluid showed 760 leukocytes/mm’, 90% mononuclears, protein 386, sugar 41 mg/100 ml, and chloride 122 meq/l.
He was treated with sodium bicarbonate
so-lution, but developed carpopedal spasm and positive Chvostek sign, which responded
poorly to administration of calcium gluconate.
Because of vomiting of coffee-ground material,
he was given milk and antacid. After receiving
fluids which provided a total calculated
correc-tion of 20 meq with bicarbonate, carbon di-oxide content was 19.1 meq/l, pH 7.67, chlor-ide 98.6 meq/l, sodium 135 meq/l, and cal-cium 7.1 mg/100 ml. Twitching, which did not respond to calcium gluconate, diphenyl-hydantoin or chlorpromazine, was finally
stopped with amytal.
Despite fluid therapy he remained alkalotic
and hypochloremic. Urine showed specific gravity 1.002, pH 6, and no sugar or albumin. Hemoglobin was 11.5 gm/100 ml, and
leuko-cyte count was 15,900/mm3 with 74%
neutro-philes, 22% lymphocytes and 4% monocytes. Twitching recurred despite magnesium sul-fate, and bloody vomitus and stool were pres-ent on the second hospital day. On the third
day the blood pH was 7.4 but chloride was
95.4 meq/l and sodium 144 meq/l; urine showed specific gravity 1.010, pH 7.5,
nega-tive protein and sugar. On the next day, serum
sodium was 132 meq/l and chloride was 90.6
meq/l, suggesting that he had a salt-losing
state due to central nervous system disease.
On the fifth day, chloride had decreased to 81.9 meq/l despite solutions of sodium chlor-ide calculated at 1.5 maintenance requirement.
The patient’s level of consciousness declined,
he became edematous, respiratory rate fell to
444
The blood pressmre then declined and he died
on the eighth day after admission, at the age
of 9 ‘ears 6 months.
Necropsy Findings
GROSS EXAMINATION : The patient was a
fairly well developed amid nourished white
male (length 108 cm; normal 127 cm) with
l)rownish pigmentation of the skin, more
marked in the exposed areas. There were no
other specific abnormal external findings. The
abdominal viscera were not remarkable in situ,
nor were the heart, lungs, and mediastinum
unusual. The spleen was small (:39 gm; normal
73 gm), and (liffl15e1V brownish on cut surface.
The liver wa not remarkable in size, and
showed fl() evidences of scarring, but was also
browner than normal. The kidneys were not
al)normal externally or on section, but the
adrenals (combined weight 7.8 gm) had diffuse
fine nodularitv of the cortices. The bladder,
testes, trachea, thyroid, gastrointestinal tract,
and pancreas showed no gross lesions. No
en-larged lymph nodes were noted, and the
thy-mus was small. Ribs and vertebrae showed no
abnormalities of conversion lines or of marrow.
Culture of the lung gave no growth.
Central Nervous System. No evidences of
recent or old meningeal hemorrhage or
in-flammation were seen and the brain was
nor-mally formed. It weighed 1,250 gm (normal
1,280 gm). The gvri of both occipital poles,
and the cerebellar folia posteriorly, seemed
small. On section, the gray and white matters
of the cerebrum were normally demarcated,
the corona radiata appearing, if anything,
rela-tivelv large. The ventricles were not dilated,
and no pigmentation of basal nuclei was noted.
The cerebellum showed relatively small folia
posteriorly, with prominent central white
mat-ter, and the pons was enlarged, pale, and firm,
with diminished prominence of normal dorsal markings. The medulla and cervical spinal cord
showed swelling of their dorsal portions by
soft tissue, darker than normal white matter,
the appearance in the medulla suggesting that
of neoplasm. Lower dorsal and lumbar regions
of the spinal cord were also examined; these
were not remarkable externally or on cut
sur-face.
MIcRoscoPIc EXAMINATION: The heart was
not unusual. The lungs showed terminal edema,
and mild nonspecific chronic pneumonitis, but
no acute pneumonia. The spleen showed
marked and the liver mild hemosiderosis. The
pigment in these organs all gave an iron stain,
and none was sudanophilic or positive by
per-formic and peracetic acid-Schiff stains. The
liver also showed mild portal fibrosis. In the
pancreas there were scattered dilated ductules,
but no areas of atrophy or fibrosis were seen,
and neither islets nor acini showed siderosis.
The gastrointestinal tract showed oiil
non-specific chronic enteritis, and questionable
fibrosis of the small intestinal submucosa. The
mventeric plexus ganglia were not abnormal,
and the nerve cells showed no demonstrable
lipidosis.
The kidneys showed diffuse cortical
inter-stitial fibrosis, plus many patches of chronic
inflammation and more marked interstitial
scarring. Many tubules and glomeruli had
thickened capsular membranes (Fig. 1) and
many distal convoluted tubules and loops of
Henle contained casts. Many loops of Henle
also showed brown granular pigment in
tubim-lar cytoplasm; this pigment (Fig. 2) was
iron-negative, sudanophilic in paraffin sections, and
weakly positive with periodic acid-Schiff (PAS)
FIG. 1. Kidney showing patchy cortical fibrosis,
irregular tubular atrophy and dilatation,
and acid permanganate-aldehyde fuchsin stains. It stamed weakly with peracetic acid-Scuff staii, but not with 1)erformic acid-Schiff, was not acid-fast, and gave moderate orange
fluorescence with ultraviolet illumination.
Thus, the pigment had the staining properties
of a chromolipid, but not of ceroid, and did
not differ appreciably from the lipid pigment
to be described in damaged areas of the brain.
The skin microscopically showed increased
melanin pigment, but no chromolipid.
The adrenals had strikingly nodular cortices
(Fig. :3), with patch acute necrosis of the
cortical cells. The appearance did not suggest
that seen in association with
Waterhouse-Friderichsen syndrome, and the fat content of
the adrenal cells was not definitely low. The
testes were severely and diffusely atrophic,
with no apparent tul)ular fibrosis (Fig. 4);
Levdig cells were not seen. Although germ
cells were apparently absent from the testes,
determination of nuclear genetic sex on
sev-eral tissues showed that the patient was
chromatin negative. The thymus showed
mod-eratelv advanced atrophy, and the thyroid mild
Fic. 3. Adrenal showing irregular nodulanity of
cortex, and variable lipid content of cortical cells,
the general cytologic pattern being that of
in-creased secretory activity. (Heniatoxylin-eosin,
x95.)
irregularity of follicles and colloid depletion
indicative of some degree of secretory activity.
The only skeletal muscle studied was
dia-phragm; it showed patchy degeneration of
single muscle fibers, but no evidences of
de-nervation atrophy. The bone marrow was
definitely reduced in cellularity, with relative
increase in the number of ervthropoietic cells,
and with prominent megakarvocytes. The
an-tenor pituitary gland was not abnormal (PAS,
phosphotungstic acid-hematoxylin, direct
aide-hyde fuchsin, and acid permanganate-aldehyde
fuchsin stains used) but the posterior pituitary
showed brown granular pigmentation of
scat-tered pituicvtes, and a few hvaline masses
similar to those described below !i other areas of the brain.
Central Nervous System. The brain and
spinal cord showed, in different areas, a
de-generative process characterized b\? varying
Fir.. 2. Granular chromolipid pigment in cyto- degrees of admixture of: 1) dem’elination;
plasm of cells of loops of Henle. (Hematoxylin- 2) gliosis; 3) deposition of brown granular
446
AMAUROTIC
IDIOCY
lic. 4. 1)iff,:se scere testicular atrophy. The few surviving ttil)tiieS arc siiiali amid widely spaced, ht 5110W lU) apparent fibrosis.
(Ileniatoxylin-eosin. >( 175.)
of the cervical cord, and the dorsolateral
P#{176}-tions of the medulla and pons were markedly
swollen b\ astrocytosis and iiiicrogliosis (Fig. 6),
InlI1V of the latter cells containing neutral fat,
readily solul)le in organic solvents, and not
stained by Luxol fast blue MBS, or PAS stains.
The rounded hvaline masses (“Schollen”)
were most numerous iii the granular layer of
the cerebellar folia and in the dentate nucleus
(Fig. 7), but were also seen in the posterior
1litt1itar, ventral thalamus , and dorsolateral
l)ortions of the pons and medulla. The were
Sudan-negative, Luxol fast l)lue negative, an(l
negative or weakly positive to PAS, in both
frozen and paraffin sections of formalin-fixed tissue. They were also negative, in paraffin
see-tions, to performic acid-Schiff, alcian blue,
direct aldehvde fuchsin, and acid
permanga-nate-aldehvde fuchsin stains, and stained very
weakly vitii toluidilie blue in 1)0th frozen and
1)araffifl sections. They con tamed no apparent
pigment, and were usually completely
homo-geneous and hvaline-looking, although a few
showed patchy vacuolatioli. \Vith the BO(liafl
and 4) formation of rounded or oval hyaline
iiiasses (“Schoilen”), apparently from axons of
nerve cells. In addition. there was marked
reduction in numbers of Purkinje cells,
neu-l00C5 of the dentate nucleus, and granular
layer cells in the cerebellum, plus focal acute
necrosis of granular layer cells, this latter
ap-l)tre11tlY a terminal j)henonienOn. The pigment
deposition was most marked in tile posterior
1)ituitarv, ventral thalamus, and palliduiii (Fig.
5); the )igIi1el1t was iron-negative,
sudano-philic in both frozen and paraffin sections, and
hasophilie (toluidine blue, basic fuchsin). It
(lid not stain with performic or peracetic
acid-Schiff, nor with Luxol fast blue MBS, and was
iot acid-fast. Its staining properties were
identical to those of the normal pigment of
the substantia nigra, as seen in the dorsal pons.
Demvelination as slight in the pallidum,
more marked in the ventral thalamus and
cerebellum, and most marked in the
dorso-lateral portions of the pons. medulla and
cervi-cal cord. The dorsal horns of the gray matter
Fic. 5. Chromolipid pigment granules in glial
cells and penivascular macrophages of pallidum.
(Luxol fast blue NIBS-periodic acid-Schiff, X
Fic. 7. I)entate nucleus of cerebellum. The
hyaline axonal masses stain snore deeply than
the nerve cell I)odies, those within the cell
layer being darker than those in the adjacent
white matter. (Phosphomolybdic acid-stannous chloride, X 175.)
protargol stain
.
11)P1reI1 t coIl tinuation of someof tIme hvaline masses into axons could he
demonstrated (Fig. 8), particularly in the
cerei)(’lluni.
No al)normal rnetachroniatie material could
l)e (lenionstrated in any area of the central
nervous SVStefli it1i toluidine blue, on both
frozen and paraffin sections, so that myelin
breakdown was apparently along normal
path-Fmc. 6. Dorsal horn of gray matter of cervical
spinal cord, showing diffuse gliosis and
capil-lary proliferation, as well as early
deniyelina-timi of the adjacent dorsal column of white
niatt(r. (Ilematoxvlin-eosin,
x
175.)Fir.. 8. Purkinje cell layer of cerebellum, show-ing 1x)sitive stain of one of the hyalmne axonal swellings ( Schollen), and continuation of axon froiii the ends of the mass. (Bodian protargol
448
AMAUROTIC
IDIOCY
ways. In frozen sections, many neurones in
the cerebral cortex contained small amounts
of sudanophilic lipid, which was not
demon-strable in paraffin sections. The neurones of
the inferior olive contained definitely increased
masses of lipid, which was negative to Luxol fast blue, and only weakly sudanophilic,
al-though strongly PAS-positive in paraffin
see-tions.
Sections of eve showed no abnormality of
nerve cells, but the choroid pigment showed
an irregular “clumped” distribution. The
corn-Innation of chromolipid deposition in thalarnus and pallidum, in combination with
demyelina-tion and gliosis of the dorsoiateral portions of
the brain stem, with marked cerebellar nerve
cell loss, and with localized hvaline axon
swellings in cerebellum, mid-brain and
brain-stem, was considered to be the process
origi-nally described by Seitelberger as that of
“spastic amaurotic axonal idiocy.”
COMMENT
As has been mentioned previously, the lesions of the central nervous system in this 9-year-old boy correspond very closely
to those described by Seitelberger’ and by
Rabinowicz and Wildi’ in patients with
“spastic amaurotic idiocy.” The
associa-tion of chromolipid deposition in the
basal nuclei, degeneration and gliosis of
the dorsal portions of the brain stem and
cervical cord, and segmental hyaline
swell-ing of axons (Schollen), appears to
con-stitute a pathognomonic pattern, even though no single feature is diagnostically
specific. This patient differs from all
pre-viously reported patients with the disease
in being a male. Because of the small
num-ber of such reported cases (six), this
ap-parent sex ratio may be fortuitous, but it
may also indicate that penetrance of the
abnormal genes is higher in females, or that males usually have somewhat different
symptoms. Thus, neither spasticity nor
amaurosis was an important clinical feature of the patient reported here, and the name of the disorder perhaps merits revision.
The lack of relevant information on other
patients with this disease makes any
analy-sis of the relation of the other findings in
this patient to the nervous system lesions
difficult. At least four such features,
how-ever, merit consideration as integral
fea-tures of the disease: the transient hypo-plastic anemia, gonadal atrophy, the changes in the kidney (including chromo-lipid deposition in loops of Henle) and the
nodular alteration of the adrenals. Except
to suggest that such processes be looked for in patients suspected of having spastic amaurotic axonal idiocy, little can be said of the gonadal and adrenal changes. Either the renal or the adrenal lesions, and very possibly both, can be considered
responsi-ble for the severe hypochloremia which
marked the terminal illness. The presence
of a chromolipid pigment in the renal
tubu-lar cells suggests that kidney biopsy or
ex-amination of urine sediment might be of value in the diagnosis of this disease. It is obvious, however, that study of other
pa-tients will be necessary before definite
rela-tion of the renal deposition of pigment to
spastic amaurotic axonal idiocy can be
established, and the reliability of renal
biopsy or urine sediment examination be
proven. It seems worth mentioning that
diagnostic changes can be seen in the
kid-neys of patients with several other diseases
of children producing neurologic
mani-festations, including lead poisoning,5
Hur-ler’s disease6 and metachromatic
leuko-encephalopathy.
SUMMARY
The clinical and pathologic findings of
a 9%-year-old white boy who suffered from
hypoplastic anemia from the ages of 8 to
26 months, and who later developed
neuro-logic manifestations of cerebellar and brain
stem dysfunction, are reported. The cen-tral nervous system showed a pattern of lesions-deposition of chromolipid pigment in basal nuclei and brain stem,
degenera-tion and gliosis of the dorsal portions of
the brain stem and spinal cord, and
seg-mental hyaline swelling of axons, especially
in the cerebellum-considered
pathogno-monic of the condition described by
Seitel-berger as “spastic amaurotic axonal idiocy.”
T. N.
HARRIS,M.D.
male recognized to have this rare familial
disease. He also showed severe testicular
atrophy, nodular alteration of the adrenal
cortex, renal cortical fibrosis and
degenera-tive changes of the renal tubules, as well
as deposition, in tile cytoplasm of cells of
the loops of Henie, of chromolipid pigment
similar to that found in the brain. Although
the relation of these other lesions to those
of the central nervous system can not be
established with certainty, the possibility
that the tubular pigment deposition has
diagnostic significance, and that the
condi-tion can be diagnosed by kidney biopsy or
examination of urine sediment, is
sug-gested.
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Stoff-wechselkrankeit der Ganglienzellen des
Zentral Nervensystems, in Reports of 5th
International Neurologic Congress,
Lis-boIl, Vol. 3, 1953.
2. Rabinowicz, T., and Wildi, E. : Spastic
amaurotic axonal idiocy. A familial
juve-nile form of a lipo-glyco-protidic
thes-aunisrnosis including a pallidal siderosis,
in Cerebral Lipidoses, Cumings,
J.
N.,and Lowenthal, A., eds. Springfield,
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Histochemi-cal properties of renal lead inclusions,
and their demonstration in urinary
sedi-ment. Am.
J.
Clin. Path., 31:499, 1959. 6. Kobayashi, N. : Acid mucopolysacchanidegranules in the glomerular epithelium in
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MEcriANIsfs OF Hypimsr.srnvrry. HENRY FORD HOSPITAL INTERNATIONAL
SYMP0s-IUM, edited by
J.
H. Shaeffer, M.D.,G. A.
Lo Grippo, M.D., and M. W. Chase,
Ph.D. Boston, Little, Brown and
Com-pany, 1959, 754 pp., $18.50.
This book represents an ambitious effort to
collect recent information in a wide area of
immunology. There are 48 individual papers
divided among 12 different sections. Thus,
al-though the title of the symposium refers only
to hypersensitivity, there are sections not only
on the specific reactions of the delayed and
immediate types of hypersensitivity and on
mechanisms which may be involved in these, or may modify them, but also on peripheral areas
such an autoantibodies, and tolerance and
re-jection of transplanted tissue. There are also
a number of groups of papers on humoral
anti-bodies, on the detection and measurement of
these, on the heterogeneity of antibodies, and
on immunologic unresponsiveness. Although this book does not purport to represent current developments in the entire field of
immu-nology, its coverage is quite broad.
The contributions are in every case by active
workers in the fields discussed, and the
em-phasis is on recent data in these areas. For
those interested in immunologic problems this collection of papers would be a useful and in-formative account of progress in many areas of immunology currently under the most active
