Sweet's Syndrome

Sweet's syndrome — also known as acute febrile neutrophilic dermatosis — is a skin condition marked by fever and painful skin lesions that appear mainly on your arms, face and neck.
The exact cause of Sweet's syndrome isn't always known. In some people, it's triggered by an infection, illness or certain medications. Sweet's syndrome can also occur with some types of cancer.

Most often, Sweet's syndrome will clear on its own in a few months or once the underlying cause is resolved or eliminated. Healing is much more rapid with treatment.

Symptoms

The most obvious signs of Sweet's syndrome are distinctive skin lesions that usually develop according to this pattern: A series of small red bumps appear suddenly on your arms, neck, face or back, often after a fever or upper respiratory infection. The bumps grow quickly in size, spreading into clusters called plaques that may be up to an inch or so in diameter. The eruptions are tender or painful and may develop blisters, pustules or even ulcers. Lesions may persist for weeks to months and then disappear on their own, without medication. With medical treatment, you're likely to be free of skin lesions in just a few days.

Other signs and symptoms of Sweet's syndrome may include:
- Moderate to high fever preceding the skin lesions
- Pink eye (conjunctivitis) or sore eyes
- Tiredness
- Aching joints and headache
- Mouth ulcers

When to see a doctorSweet's syndrome is rare. When it occurs, it often develops after an upper respiratory tract infection. If you develop a red rash that quickly grows in size soon after a bout with strep throat or another upper respiratory infection, see your doctor for appropriate treatment. Although the rash may eventually disappear without treatment, the right medication can make the rash go away in just a few days.

Sweet's syndrome may also be a reaction to a more serious condition, such as leukemia, or to certain medications.

Causes
Although Sweet's syndrome may be associated with infections, the condition itself isn't infectious. Sweet's syndrome is typically divided into three categories, depending on its associations:
Idiopathic (classical). In most cases, the cause of Sweet's syndrome isn't known (idiopathic). Idiopathic Sweet's syndrome predominantly affects women between the ages of 30 and 50, and is often preceded by an upper respiratory or gastrointestinal infection. It's also been associated with pregnancy and inflammatory bowel disease.

Malignancy-associated. In about 20 percent of cases, Sweet's syndrome is associated with cancer (malignancy), most often acute leukemia. A few cases may be associated with a solid tumor, such as breast or colon cancer. Sweet's syndrome can occur as an early sign of a cancer, after diagnosis or as a sign of a recurrence. Fever is often present but skin lesions typically aren't preceded by an upper respiratory infection, as is the case with idiopathic Sweet's syndrome. Malignancy-associated Sweet's syndrome appears to affect men and women equally but among older adults, it's more likely to occur in women.

Drug-induced. Although uncommon, Sweet's syndrome may occur as a reaction to a medication, most commonly to granulocyte colony-stimulating factor, a hormone preparation designed to increase your white blood cell count. Other medications associated with Sweet's syndrome include certain antibiotics, oral contraceptives, diuretics and anti-epileptic drugs, among others. Once the offending drug is discontinued, Sweet's syndrome usually goes away.

Risk factors
Sweet's syndrome is uncommon, but certain factors increase your risk, including:
Being a woman. Women are far more likely to have idiopathic Sweet's syndrome than men are.
Being between 30 and 50 years of age. Though older adults and even infants can develop Sweet's syndrome, the condition mainly affects women between the ages of 30 and 50.
Having other health problems. Sweet's syndrome often follows an upper respiratory infection, and many people report having flu-like symptoms before the rash appears. Sweet's syndrome can also be associated with a number of other illnesses, including inflammatory bowel disease, certain systemic infections and cancer.

Being pregnant. Some pregnant women develop Sweet's syndrome during their first or second trimester. In these cases, the condition usually clears without treatment.
A previous history of the condition. Sweet's syndrome tends to recur. About one-third of people who have had Sweet's syndrome once get it again.

Complications
There is a risk of the skin lesions becoming infected. Follow your doctor's recommendations for caring for the affected skin. The most challenging aspect of Sweet's syndrome may be in dealing with recurrences, which occur in about a third of cases. Signs and symptoms may reappear, especially if treatment is tapered off too quickly. Be certain to follow your treatment plan exactly as your doctor recommends.

Preparing for your appointment:
Your family doctor or general practitioner is likely to refer you to a dermatologist for diagnosis and treatment of Sweet's syndrome. If tests reveal an underlying condition, you'll also be referred to the appropriate specialist, such as a gastroenterologist or oncologist.
Because appointments can be brief and there's often a lot of ground to cover, it can help to be well prepared. Here are some tips to help you get ready for your appointment and what to expect from your doctor.

What you can do...Write down all your signs and symptoms — even those that seem unrelated to your rash. Sweet's syndrome can be a sign of several illnesses, so it's important that your doctor know all of your symptoms. Include key personal information, such as major stresses or recent life changes. Make a list of all medications, including vitamins, herbs and over-the-counter drugs, that you're taking. Even better, take the original bottles and a written list of the dosages and directions. If possible, take along a family member or friend. It can be difficult to absorb all the information provided to you during an appointment. The person who accompanies you may remember something that you forgot or missed.
Write down questions that you want to ask your doctor. Don't be afraid to ask questions or to speak up when you don't understand something your doctor says. Start with the problems that concern you most. If you run out of time, ask to speak with a nurse or physician's assistant or leave a message for your doctor.

If you have symptoms of Sweet's syndrome, questions you may want to ask include:
What might be causing my rash?
What tests do I need to confirm the diagnosis?
Is this condition temporary or chronic?
What is the best course of action?
What are the alternatives to the primary treatment approach that you're suggesting?
I don't like the idea of taking steroids. Are there other medications you can prescribe?
Is there a generic alternative to the medicine you're prescribing me?
What if I just wait to see if my signs and symptoms go away on their own?
What to expect from your doctorYour doctor is likely to ask you a number of questions, such as:
When did your symptoms start?
Did they come on suddenly or gradually?
What did the rash look like when it first appeared?
Is the rash painful?
What, if anything, makes it better?
What, if anything, makes it worse?
Were you sick before the rash started?
Do you have other symptoms that started about the same time?
What medications do you take?

Tests and diagnosis
Your dermatologist can usually diagnose Sweet's syndrome simply by looking at the lesions. But you're likely to have certain tests to rule out conditions that have similar symptoms and to search for the underlying cause.

These tests include:
Blood tests. A small sample of your blood may be sent to a laboratory where it's checked for an unusually large number of white blood cells and certain blood disorders.
Tissue sample. Your doctor may remove a small piece of affected tissue (biopsy) for examination under a microscope. The tissue is analyzed to determine whether it has the characteristic abnormalities of Sweet's syndrome. The area where the sample is taken is numbed, and a small piece of skin is removed with an instrument that looks like a small cookie cutter — a procedure called a punch biopsy. You're not likely to need stitches, and the incision should heal without scarring.

Treatments and drugs
Left untreated, Sweet's syndrome not associated with a more serious condition may disappear on its own within one to three months. Medications can improve skin lesions and associated symptoms in just two or three days, with the worst of the lesions disappearing within one to four weeks. This is true even for malignancy-associated Sweet's syndrome, although treatment or remission of the associated cancer will help, too.

With or without treatment, the lesions rarely leave a mark or scar when they eventually disappear. Your doctor may advise continuing treatment because recurrence of the condition is common.

Medications Systemic corticosteroids (prednisone or prednisolone) are generally very effective in treating Sweet's syndrome. You typically take these oral anti-inflammatory medications for about four to six weeks. Topical corticosteroids may be used to provide immediate relief of swelling.

Other first line medications your doctor may use include potassium iodide therapy, which you take as an oral tablet or as drops, and colchicine, which has anti-inflammatory properties. Follow your doctor's instructions exactly when taking these medications and be sure your doctor knows about any other medications you're taking, to avoid harmful drug interactions.
Lifestyle and home remedies

If you have Sweet's syndrome, it's important to treat your skin gently. These steps can help reduce additional injury to the skin:
Avoid injury to your skin. Wear protective clothing if you think you might injure or damage your skin.

Apply sunscreen. Use sunscreen with a sun protection factor (SPF) of 15 or greater before you head outdoors.

References
Farhi D, et al. The neutrophilic dermatoses. Dermatology Nursing. 2008;20:274.
Moschella SL. Neutrophilic dermatoses. http://www.uptodate.com/home/index.html/. Accessed April 5, 2010.
Sweet's syndrome: A dermatologic condition associated with fever and frequently confused with an infectious process. In: Mandell GL, et al. Mandell, Douglas, and Bennet's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa.: Churchill Livingstone Elsevier; 2010. http://www.mdconsult.com/book/player/book.do?method=display&type=bookPage&decorator=header&eid=4-u1.0-B978-0-443-06839-3..00052-7--s0060&uniq=193269557&isbn=978-0-443-06839-3&sid=978680989#lpState=open&lpTab=contentsTab&content=4-u1.0-B978-0-443-06839-3..00052-7--s0060%3Bfrom%3Dtoc%3Btype%3DbookPage%3Bisbn%3D978-0-443-06839-3. Accessed April 5, 2010.
Cohen PR. Sweet's syndrome — A comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet Journal of Rare Diseases. 2007;2:34.
Franks AG Jr. Skin manifestations of internal disease. Medical Clinics of North America. 2009;93:1265.
Colchicine: Drugdex Evaluations. Micromedex Healthcare Series. http://www.micromedex.com. Accessed April 5, 2010.
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June 24, 2010
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Total Anomalous Pulmonary Venous Return

Total anomalous pulmonary venous return (TAPVR) is a rare congenital heart defect that causes cyanosis or blueness. The basic problem is that the blood flow coming back from the lungs (which is full of Oxygen) through pulmonary veins is diverted to the right atrium so that there is complete mixing of blood (red and Blue) within the heart. These abnormalities are divided into two major groups - obstructed and unobstructed. Unobstructed is the most common and this frequently involves the common pulmonary vein being connected by an abnormal vertical vein to the superior vena cava and emptying into the right atrium. There can also be a direct connection of the common pulmonary vein to the right atrium. Either way this causes complete mixing of the blood within the right atrium. These babies are usually a little blue at birth, but not necessarily very sick. Many times they will go home from the nursery and be found to be breathing fast by the pediatrician. This is because the mixing of blood causes the heart to work harder than normal. This is usually relatively easy to fix. It does involve open-heart surgery. Once fixed, the heart is for the most part normal.

Obstructive veins are another matter. These babies are usually very ill at birth. In this situation the blood flow leaving the lungs through the pulmonary veins is not only going to the wrong place but is at least partially blocked, this makes it harder for blood to enter the lungs. Most of the time these abnormal connections occur in the liver. They can occur in the upper part of the chest as well. When the veins are obstructed It also makes the pressure in the right ventricle higher than normal. When blood cannot easily enter the lungs the babies are very blue because not enough blood goes to the lungs and there is a lot of mixing of blood (blue blood with red blood) at the level of the PDA and Foramen Ovale (opening in wall between the upper chambers of the heart). Because not enough oxygen is being circulated in the body the baby becomes acidotic and the muscle tissue and kidneys, etc. do not work well. When the oxygen level is low, the arteries in the lungs tend to tighten up, making it harder for blood to be pumped through the lungs and thus the situation even worse. When the lungs are full of blood they become stiff, making it harder to breathe. Very frequently in this condition the actual veins draining back from the lungs are smaller than normal. This is because they never developed normally in the first place. This condition is lethal unless it can be fixed quickly after diagnosis.

Most of the time we are able to diagnose this condition by echocardiogram. One can see the abnormal flow patterns of blood coming from the lungs into the SVC or we can see abnormal patterns in the liver, which is where most of the obstructed veins return. We also look to see if we can see the normal pulmonary veins returning to the left atrium. We can measure oxygen levels in the right atrium with an umbilical catheter and this will be abnormally high.

TAPVR can closely mimic a condition called persistent fetal circulation. In this case the pulmonary veins are normal but very little blood flow is going to the lungs. This can sometimes occur with stressed or infected babies and can be very difficult to treat. The pressures in the lungs can be very high and little blood flow goes through the lungs. As with TAPVR this is a lot of mixing of blood within the heart and the oxygen level can be quite low. This condition can be treated with a ventilator, pulmonary vasodilators, nitric oxide and sometimes ECMO. It can be very difficult to distinguish these two conditions as they have many similar clinical features.

TAPVR is not something that can be treated medically. The longer the delay in surgery, the worse the outcome. This condition is frequently associated with other rare conditions such as dextrocardia, and ambiguous situs. In this situation a baby's internal organs can have either two right sides or two left sides.

The outcome for unobstructive TAPVR is usually quite good. The outcome of obstructive TAPVR can vary and ultimately depends on the overall size of the pulmonary veins. Many attempts have been made to enlarge these surgically and with balloons and stents but the results are seldom satisfactory.

If you have any questions, please ask one of the doctors.

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Excercise-Intuced Anaphylaxis (EIA)

Background
Exercise-induced anaphylaxis (EIA) is a syndrome in which patients experience the symptoms of anaphylaxis, which occur only after increased physical activity. The symptoms include pruritus and urticaria (typically with giant hives), and, without emergency intervention, the patient may develop hypotension and collapse. Now increasingly recognized as more children and teenagers participate in physical activities and sports, exercise-induced anaphylaxis may become more common in the future. Those affected by the syndrome are typically accomplished athletes and have a history of atopy, but anyone can be affected.
The types of physical activities that have triggered episodes of exercise-induced anaphylaxis have included walking, dancing, racquet sports, swimming, jogging, bicycling, skiing, basketball, and sprinting. Hot humid weather and cold weather can precipitate episodes in some patients. If a patient has recurrent exercise-induced anaphylaxis, the episodes tend to be worse in the summer months. The first reported case of exercise-induced anaphylaxis was in 1979 by Maulitz and coworkers and was food-related, occurring in a 31-year-old patient who had ingested shellfish prior to long-distance running.1 Since then, many different allergens have been reported in the literature to have caused exercise-induced anaphylaxis, including shrimp, oyster, celery, cheese sandwiches, pizza, wheat gliadin,2 eggs, peaches, grapes, pomegranites,3 chick peas,4 pears, poppy seeds, soybean,5 and snails (which have been reported to have cross-reactivity with dust mites).
In 1980, Sheffer and Austen provided the first report of patients with exercise-induced anaphylaxis.6 Sixteen patients, aged 12-54 years, experienced exercise-induced anaphylaxis without a specific allergen exposure. Ten of these patients had onset of exercise-induced anaphylaxis in their teenage years, indicating that those who care for pediatric patients should be aware of this syndrome.
Exercise-induced anaphylaxis has been categorized in a few different ways in the literature. Classic exercise-induced anaphylaxis is the most common type. Sheffer and Austen (1980) originally described 4 phases in the sequence of symptomatology of classic exercise-induced anaphylaxis.6 A prodromal phase is characterized by fatigue, warmth, pruritus, and cutaneous erythema. The early phase follows, with the urticarial eruption that progresses from giant hives (about 10-15 mm in diameter) to become confluent and may include angioedema of the face, palms, and soles. Then, the fully established phase occurs, which can include hypotension, syncope, loss of consciousness, choking, stridor, nausea, and vomiting and can last 30 minutes to 4 hours. The final phase is the late or postexertional phase, which is characterized by prolonged urticaria and headache persisting for 24-74 hours.
Another type of exercise-induced anaphylaxis is variant-type exercise-induced anaphylaxis, which is similar to classic exercise-induced anaphylaxis, except the typical giant hives are not observed. In their place are small punctate skin lesions, more typical of cholinergic urticaria, but the syndrome does lead to hypotension and collapse if allowed to progress. The variant type of exercise-induced anaphylaxis accounts for approximately 10% of cases.
Familial exercise-induced anaphylaxis has been described involving patients with a family history of exercise-induced anaphylaxis and atopy. No inheritance pattern has been established.
Two forms of food-dependent exercise-induced anaphylaxis have been described. Inherent in the definition of food-dependent exercise-induced anaphylaxis is that the food or exercise alone does not produce symptoms. First, specific-food exercise-induced anaphylaxis in which a specific food is known to be the offending allergen is recognized. Second, nonspecific-food exercise-induced anaphylaxis in which no specific food is known, but eating any food prior to exercise causes symptoms of exercise-induced anaphylaxis is also recognized.7
The last type of exercise-induced anaphylaxis described is medication-dependent or drug-dependent exercise-induced anaphylaxis. This category includes patients who develop the syndrome only after ingesting a specific medication and then exercising. The offending medications that have been reported include nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, antibiotics, and cold remedies.

Pathophysiology
In exercise-induced anaphylaxis, an exercise-induced lowering of the mast cell degranulation threshold occurs, which causes the release of histamine and other mediators and leads to the progression from pruritus and urticarial rash to the symptoms of anaphylaxis. In the food-dependent subset, this process is influenced by immunoglobulin E (IgE) mast cell sensitization by a known or unknown food. If the offending food is known, the amount of the specific food ingested has an effect on whether the patient has symptoms. The mechanism by which exercise lowers the mast cell degranulation threshold is unknown. Previous observations suggest that increased physical activity has a direct effect on mast cell releasability and does not result in an increased sensitivity to histamine.
Once the histamine and other mast cell mediators, including leukotrienes, are released, they cause the smooth muscle contraction responsible for the wheezing and GI symptoms. The histamine and other mast cell mediators also cause the vascular dilatation that leads to the escape of plasma into the tissues, causing urticaria and angioedema, and results in hypotension and shock.8,9

Frequency
United States
Prevalence is not well established. In one study, 9% of total episodes of childhood anaphylaxis and 20% of episodes in children older than 8 years were triggered by exercise.
International Case reports from Germany, Italy, Japan, United States, and Thailand are provided in the literature.

Mortality/Morbidity
Deaths of children have been reported, but they are rare. Infrequently, patients must alter their lifestyle and physical activity significantly; in some patients, the syndrome causes them to be unable to perform daily activities without the risk of anaphylactic syndrome.

Race
No racial predilection is known.

Sex
One study showed a slight male predominance, but most other studies show no overwhelming difference between sexes.

Age
Exercise-induced anaphylaxis has been reported from as young as 4 years into adulthood. In a study of 16 patients, 10 patients (63%) had onset in their teenage years.

Clinical History
Pediatric patients with exercise-induced anaphylaxis (EIA) typically are athletic or involved in school or otherwise organized sports, and they typically have a history of atopy and/or a family history of atopy or possibly of exercise-induced anaphylaxis.
Typical episodes occur after exercise on a particularly hot, humid, or cold day.
History of ingesting aspirin or other nonsteroidal anti-inflammatory drug (NSAID), a meal, or a specific food prior to exercising may be noted.

In women, the episodes can be more frequent and more severe before and during menstrual cycles.

The history of an episode most likely includes the initial pruritus and giant hives associated with the onset of the symptoms.

As the syndrome progresses, the patient may report nausea, cramping, diarrhea, vomiting, tinnitus, vertigo, pruritus, difficulty breathing, chest tightness, and wheezing; a syncopal episode may occur.

The history may be obtained from a paramedic who responded to the collapse of a child. In this case, the patient's history may include loss of consciousness or variable consciousness.
In several minutes or hours after the episode, the patient may report only a headache that can persist for as long as 3 days.

Physical
The physical examination should start with the airway, breathing, and circulation (ABCs).
The most emergent assessments are those of airway maintenance and level of consciousness. One must rule out laryngeal obstruction.
Simultaneously assess for hypotension.
The rest of the physical examination should include looking for the typical features of exercise-induced anaphylaxis, including urticaria and giant hives, angioedema, wheezing, and stridor.

Causes
Risk factors for exercise-induced anaphylaxis include personal or family history of exercise-induced anaphylaxis or atopy, male sex (in one study), exposure to food allergen, and extremes of weather.

Beta-blocker medications can aggravate anaphylactic episodes.

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I-Cell Disease (Mucolipidosis II)

Summary
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.

Case report
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
refused.

Discussion
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
normal.
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
brain extracts.


References
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,
59, 1097.
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.