I-cell disease is an example of the mucolipidoses, a
group of diseases which show features of both the
mucopolysaccharidoses and the sphingolipidoses. A
clinical description is given of a child suffering from
this condition. The diagnostic criteria are discussed,
as well as some of the necropsy findings.
THE genetic mucolipidoses are a group of diseases
which show the symptoms and signs of both the
mucopolysaccharidoses and the sphingolipidoses
(Table 1). Some of them such as Gm2 gangliosidosis
and infantile sulphatidosis are related to known
enzyme defects, but in others the cause is unknown.
Among the latter some of the affected children have
been described as Hurler's variants as they show
many of the features of Hurler's syndrome, but
excrete normal amounts of urinary mucopolysaccharides.
M.W. born 29 May 1967.
The child was referred to Booth Hall Children's
Hospital, Manchester, at the age of 2- years. She
had been born at home and was the second child in
the family, the older sibling having developed
normally. The pregnancy and birth were normal.
Multiple deformities had been recognized from birth
and she had been treated for a dislocation of the
right hip. At the time of her referral she could not
sit up herself and made no effort to stand. In general
development was around 8-9 months. Three times
in the past year the child had lost consciousness and
become cyanotic. There was no other past history or
family history of note.
On examination the unusual appearance of the
child was highly suggestive of gargoylism (Figs. 1
and 2). The bridge of the nose was broad and
flattened, the nostrils anteverted, and the tongue
was large. The eylids were puffy, the eybrows prominent,
and the cheeks were highly coloured. The
skin was coarsened. The abdomen was protuberant
and chest expansion was limited. There was flattening
of the left side of the skull and a fairly prominent
lumbo-dorsal kyphosis. There was fair movement in
the legs and feet, but the gluteal muscles appeared
to be weak. The right thumb was flexed in the palm
and could not be extended or abducted. Both hips
were held in about 45° of abduction by contractures,
probably in the abductor muscles. There was no
clouding of the cornea and the optic fundi appeared
normal. Muscle tone was slightly reduced, but the
tendon reflexes were present and equal. The liver
was enlarged one and a half finger's breadth, but the
spleen was not palpable, and there was no evidence
of cardiac involvement.
Over the next 2 years the child was greatly
troubled by chest infections, sometimes severe
enough to be classified as broncho-pneumonia. She
showed some evidence of development, and began
to stand in splints and seemed to benefit from wearing
a spinal jacket. She started to say a few words.
At the age of 2 years 7 months the patient weighed
7-05 kg (third percentile at this age 10-4 kg), and her
height was 70-1 cm (third percentile at this age
83 cm). The GQ on the Griffiths Mental Development
Scale was 27-2. X-ray of the skull showed very
marked asymmetry. On X-ray of the spine and pelvis
there was scoliosis convex to the left, and widening
of the interpedicular spaces in the lumbar spine
(Fig. 3). The posterior borders of the vertebral
bodies in the lumbar spine were concave. The proximal
ends of both the femora were constricted (Fig. 4).
The X-rays of the hands showed that the metacarpal
and the phalangeal medullary cavities were widened.
The cortices were very narrow and thin. The lower
ends of both the ulna and radius were tapered. The
EEG was characterized by a generalized increase of
slow wave activity. There were no epileptic discharges.
There was no excess excretion of mucopolysaccharides
in the urine. Abnormal vacuoles were
found in approximately 30% of mononuclear cells.
No evidence of metachromasia was found. Some
granules in the monocytes were Sudan black positive.
Bone marrow aspirations yielded dry taps. The urine
amino acid chromatogram was normal, as were the
liver function tests. On one occasion the plasma true
glucose was 20 mg/100 ml, but the presence of hypoglycaemia
was not confirmed on a number of other
occasions. Fibroblast cultures were attempted but
were unfortunately unsuccessful. Plans had been
made to repeat these cultures when the child was
admitted to hospital with broncho-pneumonia and
died soon afterwards. Permission for necropsy was
The name 'I-cell disease' was derived from the
striking granular inclusions seen in the cultured
fibroblasts from children suffering from this syndrome.
From the few reported cases it seems likely
that the condition is inherited as an autosomal
recessive. Slow development is recognized early in
life, as well as the hypotonia. Congenital dislocation
of the hips, herniae, and hyperplasia of the gums are
also a feature. Recurrent upper respiratory tract
infection seems to be a characteristic feature, and
often a cause of death when complicated by congestive
heart failure. Development does not seem to
proceed further than sitting and standing without
support, and a few social responses such as smiling
and early vocalization. Unaided walking is not
accomplished, nor is toilet-training or self-feeding.
The affected children do not seem to survive more
than a few years (Leroy et al., 1971).
The appearance of the child becomes strikingly
similar to children with Hurler's syndrome. The
tongue is large, the earlobes fleshy, the forehead
high, the epicanthic folds prominent, the bridge of
the nose flat, the nostrils anteverted, and the upper
lip elongated (Sprangler & Wiedemann, 1970a). In
fact this is the diagnosis likely to be made. Apart
from the facies, dwarfed stature and severe retardation,
there is kyphoscoliosis, limited joint mobility
with claw hands, and sometimes enlargement of the
liver and spleen; but no clouding of the corneae.
The X-ray findings are somewhat similar as well.
There is marked periostieal new bone formation.
The tubular bones of the arms are short and plump.
The metacarpals are irregular and expanded and the
phalanges are bullet-shaped. The distal ends of the
radius and ulna are tilted. The vertebral bodies are
short and rounded and there may be beaking of the
last dorsal and first lumbar vertebrae. The ribs are
broad and the cranial vault is thickened. However,
the mucopolysaccharide excretion in the urine is
The peripheral lymphocytes and monocytes are
vacuolated and finely vacuolated cells are present in
the bone marrow. Cultured fibroblasts contain
coarse, regular, refringent inclusions staining blue
with toluidine blue, which are PAS and Sudan black
positive (Sprangler & Wiedemann, 1970b). Special
staining may also reveal metachromasia, indicating
that they contain mucopolysaccharides as well as
lipids (Matalon et al., 1968).
At necropsy foam cells are found in the endocardium,
lungs, spleen, liver, kidneys, adrenals and
aorta. Electron microscopy does not reveal the lipid
inclusions (zebra bodies) typical of Hurler's syndrome.
The lipid content of the tissues is generally
normal, ecept for some increase in total values
(Leroy et al., 1971). Liver acid P-galactosidase
activity has been found to be decreased, with hyperactivity
of a number of other enzymes (Tondeur
et al., 1971). Although the findings so far suggest a
storage disease involving both lipids and mucopolysaccharides
no definite cause can yet be suggested.
The differentiation from Hurler's syndrome is
made by the normal urinary excretion of mucopolysaccharides.
A somewhat similar clinical picture
occurs in mucolipidosis I or lipomucopolysaccharidosis,
but the features of gargoylism are not so marked
and the course of the disease is much more protracted.
Gm,-gangliosidosis, type I, has also been
referred to as pseudo-Hurler's syndrome because of
the appearance of the affected child, but the diagnosis
of this disease is confirmed by the abnormal
ganglioside pattern on thin layer chromatography of
LEROY, J.G., SPRANGLER, J.W., FEINGOLD, M., OPITZ, J.M.
& CROCKER, A.C. (1971) I-cell disease: a clinical picture.
Pediatrics, 79, 360.
MATALON, R., CIFONELLI, J.A., ZELLWEGER, H. & DORFMAN,
A. (1968) Lipid abnormalities in a variant of the Hurler's
syndrome. Proceedings of the National Academy of Science,
SPRANGLER, J.W. & WIEDEMANN, H-R. (1970a) The genetic
mucolipidoses. Neuropddiatrie, 2, 3.
SPRANGLER, J.W. & WIEDERMANN, H-R. (1970b) The genetic
mucolipidoses. Humangenetik, 9, 113.
TONDEUR, M., VAMAS-HURWITZ, E., MOCKEL-POHL, S.,
DERENME, J.P., CREMER, N. & LOEB, H. (1971) Clinical,
biochemical, and ultrastructural studies in a case of
chondrodystrophy presenting the I-cell phenotype in
tissue culture. Pediatrics, 79, 366
Information obtained from:
IINEIL GORDONM.D., F.R.C.P.
Wednesday, April 14, 2010