The fish odor syndrome

The fish odor syndrome

Also known as:

The fish malodor syndrome

Stale fish syndrome

Trimethylaminuria (TMAU)

The fish odor syndrome is a metabolic disorder characterized by the presence of abnormal amounts of the dietary-derived tertiary amine, trimethylamine, in the urine, sweat, expired air, and other bodily secretions. It affects men, women and children, from newborns to seniors, all races and ethnicities, in most countries around the world. Trimethylamine itself has the powerful aroma of rotting fish, and this confers upon an individual a very unpleasant body odor resembling that of rotting fish.

These “greater-than-normal” amounts of trimethylamine are present due to a failure in removing it via the usual oxidation route to the non-odorous metabolite, trimethylamineN-oxide, owing to a mismatch in the enzymes capacity to undertake this reaction and the substrate load it has to process.

Earlier thinking had associated fish malodor syndrome with Turner's and Noonan's syndromes but subsequent experience showed that this was incorrect.

Incidence of Fish Odor Syndrome:

In terms of frequency of occurrence, it appears that it should no longer be regarded as a “rare” disorder but more appropriately as an “uncommon” one. As of the present, it would seem that well over 200 cases of the condition have been described on a world-wide basis, and this figure is almost certainly underestimated.

The information available to date shows that the metabolic syndrome has been found in several countries, and the bias at the moment seems to be in favor of those areas that have populations derived from British/Scottish/Irish descent, but this leaning is probably more apparent than real. The condition has been observed in both males and females, although overall there appears to have been a preponderance of females reported with this condition.

Types of Fish Odor Syndrome:

 It appears that there are two major subtypes of fish malodor syndrome: first, those forms that are related to a dysfunction of the normal enzyme activity due to genetic, hormonal, or inhibitory-chemical influences; second, those forms arising from substrate overload of the enzyme activity (normal or depressed) such as an excess of dietary precursors of trimethylamine or variations in the gut microflora resulting in enhanced liberation of trimethylamine.

Proposed classification of various types of fish malodor syndrome

1. Primary Genetic Form.

In recent years, it believed that the flavin monooxygenase (FMO¹) family is responsible for this reaction. The unraveling of the isoenzymic nature of the human flavin monooxygenase system has been achieved over the past decade as well as details of their individual molecular characterization. Briefly, this has shown that there are five distinct members of the human flavin monooxygenase family [FMO1, FMO2, FMO3, FMO4, FMO5, FMO6], which can vary in terms of their functional activities and tissue expression. The form that is most abundant in human liver and appears to be most closely involved in the N-oxidation of trimethylamine is flavin monooxygenase 3 (FMO3), and for this reason the molecular identification of candidate mutant forms has centered on this isozyme and with considerable success.

Point mutations of human FMO3 associated with fish malodor syndrome

2. Acquired Form.

There are more than three cases known of acquired types of fish odor syndrome. There was no previous history in childhood and there was no familial background to the disorder. What appeared common to the three cases was evidence of hepatitis, possibly viral, in adult life and this may have been responsible for precipitation of the condition possibly by insertion of viral DNA into the genome thereby affecting normal expression of the human FMO3 gene.

3. Transient Childhood Forms.

A preterm infant (29-weeks old) who developed a fish odor while being fed a choline-containing food supplement has been described. When the choline supplement was withdrawn the odor disappeared, and it failed to reappear at 8 months of age when the supplement was reinstituted. When the supplement was given to three other preterm infants of similar weights and ages, one of these developed a fish odor. The authors attributed the fish odor associated with the choline-containing supplement to the immaturity of the N-oxidase enzyme. Since then, other cases of pediatric fish malodor syndrome have been described. During early childhood a transient or mild form of trimethylaminuria may occur. Molecular analyses in some cases can reveal compound heterozygosity for several mutations. Recent studies suggest that both severe and variant mild trimethylaminuria is much more common than hitherto recognized.

4. Transient Form Associated with Menstruation.

Several of our female patients told us anecdotally of how their fishy odor seemed to intensify with the onset of menstruation. A subsequent study of a single female fish malodor patient showed that her trimethylaminuric condition deepened just before the onset of menstruation and that this biochemical feature related closely to her own subjective description. A systematic study has confirmed that in normal healthy women of menstruating age there occurs a short episode of trimethylaminuria just at the onset of and during menstruation that then disappears.

5. Precursor Overload.

A few cases of a transient form of the fish malodor syndrome have been attributed to precursor overload thereby saturating the existing levels of flavin monooxygenase. Trimethylamine is mostly derived from dietary precursors such as choline, carnitine, and trimethylamineN-oxide through enterobacterial metabolism. Exposure to unusually high levels of such precursors may hasten a fish malodor syndrome especially if the individual is a haplotype for certain mutations. Large oral therapeutic doses of choline (8–20 g/day) have been used to treat Huntington's chorea, and although there was some improvement in the clinical picture, patients complained of a striking fish-like odor, which was attributable to the generation of excessive amounts of trimethylamine that exceeded their enzyme's capacity to oxidize it to the non-offensive N-oxide. It is noteworthy that the precursors of trimethylamine, choline and lecithin, sometimes recommended in quite high doses in health foods, food supplements, and alternative diets could lead to the problems outlined above.

Diagnosis

The diagnosis was made on the basis of clinical symptoms and biochemical assays of urine samples for either trimethylamine alone or in combination with its N-oxide metabolite. An oral challenge test involving the administration of 600 mg of trimethylamine has also been found useful for investigating family pedigrees and identifying carriers of the metabolic disorder. However, there could remain difficulties in identifying some of the other forms particularly those arising from various haplotype combinations or nongenetic causation. Basically, one has to recognize that trimethylaminuria/fish malodor syndrome can arise from the interaction of two entities, namely a dysfunctionalN-oxidation capacity (owing to genetic or nongenetic reasons)

And the burden of trimethylamine available to be oxidized.

Treatment

There has been no systematic evaluation of the various treatments for the fish malodor syndrome. Many of the reports are anecdotal in nature or involve just small groups of patients. Attempts to reduce the intake of precursors of trimethylamine such as carnitine and choline, through dietary management, appear to have been successful in some patients but not in all. It appears likely that dietary management might be most effective in mild to moderate forms of fish odor syndrome arising from particular mutations or haplotypes. Occasionally, a short course of neomycin and metronidazole to reduce the activity of the gut microflora and suppress the generation of trimethylamine may be effective in some cases.

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Sweet's syndrome

Also known as acute febrile neutrophilic dermatosis, or Gomm-Button disease.

Sweet's Syndrome which happened in 1 on 9 million is characterized by a constellation of clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis.

The syndrome was first described in 1964 by Dr Robert Douglas Sweet. It was also known as Gomm-Button disease in honour of the first two patients Dr Sweet diagnosed with the condition.

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.

Signs and symptoms of Sweet's syndrome may include:

·                                 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.

·                                 Moderate to high fever preceding the skin lesions

·                                 Pink eye (conjunctivitis) or sore eyes

·                                 Tiredness

·                                 Aching joints and headache

·                                 Mouth ulcers.

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:

1-     Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately one-third of patients with CSS experience recurrence of the dermatosis.

2-      The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer. Hence, MASS can be the cutaneous harbinger of either an undiagnosed visceral malignancy in a previously cancer-free individual or an unsuspected cancer recurrence in an oncology patient.

3-      Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, Other medications associated with DISS  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 factots:

-          Being a woman

-          Age between 30 – 50, 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 URTI, 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

-          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.

The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Clinical and laboratory evidence suggests that cytokines have an etiologic role. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. After initiation of treatment with systemic corticosteroids, there is a prompt response consisting of dramatic improvement of both the dermatosis-related symptoms and skin lesions. Topical application of high potency corticosteroids or intralesional corticosteroids may be efficacious for treating localized lesions. Other first-line oral systemic agents are potassium iodide and colchicine. Second-line oral systemic agents include indomethacin, clofazimine, cyclosporine, and dapsone. The symptoms and lesions of Sweet's syndrome may resolved spontaneously, without any therapeutic intervention; however, recurrence may follow either spontaneous remission or therapy-induced clinical resolution

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

Did you ever had sweet's syndrome before ?? please leave comment to let other patients know that they are not alone.

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Broken heart syndrome

Broken heart Syndrome is also known as:

· neurogenic myocardial stunning,

· stress cardiomyopathy

· stress-induced cardiomyopathy,

· transient left ventricular apical ballooning,

· "ampulla" cardiomyopathy

· Tako-tsubo syndrome

Broken heart Syndrome is an increasingly reported syndrome characteriz

ed by transient apical or midventricular left ventricular dysfunction that mimics myocardial infarction (MI), but in the absence of significant coronary artery disease.

CLINICAL PRESENTATION — The clinical presentation of stress-induced cardiomyopathy is similar to that of an acute MI, usually with ST elevation . The most common presenting symptom is acute substernal chest pain, but some patients present with dyspnea, shock, or electrocardiographic abnormalities.

The range of findings from these reports is illustrated by the following:

Electrocardiographic abnormalities are the most common finding. ST segment elevation was present in 82 percent of patients (208 of 255) in the systematic review. Among these patients, ST elevations were most common in the anterior precordial leads (82 percent or 172 of 205 patients). Additional ECG abnormalities have also been described, including ST segment depression, T wave inversion, QT interval prolongation, and abnormal Q waves are also seen in some patients.

Cardiac biomarkers are frequently elevated. However, the enzyme elevations are typically mild, which is inconsistent with the often severe hemodynamic compromise. In the systematic review, among studies that measured cardiac troponins or creatine kinase MB, these levels were elevated in 86 and 74 percent of patients, respectively.

Left ventriculography or echocardiography usually show the characteristic apical ballooning with akinesis or dyskinesis of the apical one-half to two-thirds of the LV . Overall systolic function is reduced, and the reported average LVEF has ranged from 20 to 49 percent. In separate reports of ten other cases, ballooning has involved the middle or basal portions of the left ventricle but not the apical segment . No obvious mechanism for this difference in location has been identified.

In the systematic review, transient LVOT obstruction was reported in 16 percent of the patients (21 of 133) who underwent left ventriculography. In some cases, this is accompanied by systolic anterior motion of the mitral valve, similar to that seen in hypertrophic cardiomyopathy.

Reversible perfusion abnormalities in the left ventricular apex have been documented, while

magnetic resonance imaging typically shows mid and apical LV segmental wall motion abnormalities, often in multiple coronary territories without delayed hyperenhancement of involved regions.

Diagnosis — The diagnosis of stress-induced cardiomyopathy should be suspected in postmenopausal women who present with an acute coronary syndrome after intense psychologic stress in whom the clinical manifestations and ECG abnormalities are out of proportion to the degree of elevation in cardiac enzymes.

ECG1

ECG2

ECG3

Left ventricular apical ballooning or midventricular hypokinesis is usually seen on left ventriculography or echocardiography. In a minority of cases (40 percent in one report), transient left ventricular hypokinesis is midventricular ("atypical") rather than apical ("typical) .

Coronary angiography, by definition, reveals no critical coronary lesions. However, in addition to stress-induced cardiomyopathy, a number of other syndromes have been associated with ST segment changes in the absence of significant coronary artery disease, including cardiac syndrome X, variant (Prinzmetal's) angina, and cocaine abuse.

The systematic review cited above proposed the following four diagnostic criteria, all of which must be met :
1- Transient akinesis or dyskinesis of the apical and midventricular segments in association with regional wall motion abnormalities that extend beyond the distribution of a single epicardial vessel
2- Absence on angiography of obstructive coronary artery disease or evidence of acute plaque rupture
3- New ST segment elevation or T wave inversion on the ECG
4- Absence of recent significant head trauma, intracranial bleeding, pheochromocytoma , myocarditis, or hypertrophic cardiomyopathy .

There are no standard treatment guidelines for treating broken heart syndrome. Treatment is similar to treatment for a heart attack until the diagnosis is clear. Most people stay in the hospital while they recover.

Once it's clear that broken heart syndrome is the cause of your symptoms, your doctor will likely prescribe heart medications for you to take while you're in the hospital, such as angiotensin-converting enzyme (ACE) inhibitors, beta blockers or diuretics. These medications help reduce the workload on your heart while you recover and may help prevent further attacks. Many patients make a full recovery within one to two months.

Procedures that are often used to treat a heart attack, such as balloon angioplasty and stent placement, or even surgery, are not helpful in treating broken heart syndrome. These procedures treat blocked arteries, which are not the cause of broken heart syndrome. However, coronary angiography is often used to diagnose exactly what's the cause of the chest pain.

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