Dimethylsulfidemia

Dimethylsulfidemia is a pathological sign, and can be defined as > 7 nM dimethyl sulfide in peripheral venous blood. There are several known causes, but it is suggested that a newly identified metabolic condition is responsible for the majority of cases. Furthermore, there is evidence that the majority of cases of extra-oral (outside the mouth) blood borne halitosis are caused by dimethylsulfidemia. The mechanism of this relationship is thought to be related to the fact that dimethyl sulfide is subject to pulmonary excretion, and hence is transferred to the exhaled breath via gas exchange.
Physiological concentrations of dimethyl sulfide
In health, dimethyl sulfide is present at low levels. Specifically, < 7nM in blood, < 3 nM in urine and 0.13 - 0.65 nM on expired breath.
Differential diagnosis
Dimethylsulfidemia is a sign, not a diagnosis. There are several known causes, however the most common cause appears to be a new metabolic condition which is currently being researched.
Metabolic
Metabolic causes of dimethylsulfidemia can be classified as disorders of transsulfuration, however the exact pathogenesis of the newly identified metabolic condition awaits further research.
Hypermethioninemia
Hypermethioninemia is an excess of the amino acid methionine. Hypermethioninemia itself has several known causes. Methionine is normally metabolised in a pathway resulting in cysteine. When there is insufficiency of this pathway (usually related to specific enzyme deficiencies), methionine can become elevated. Dimethyl sulfide can be synthesized from methionine and so when there is hypermethioninemia, there will be accompanying dimethylsulfidemia.
Newly identified metabolic condition resulting in dimethylsufidemia
Evidence suggests that dimethyl sulfide is the leading cause of blood borne halitosis, and furthermore that this appears to be due to a previously unknown metabolic condition. This metabolic condition may affect some 0.25-1.5% of the general population, however these estimates are based on a small cohort study.
Systemic
Fetor hepaticus
Fetor hepaticus is the name given to the breath of patients with liver failure. Traditionally this was attributed to ketones and ammonia, however more recent evidence shows that dimethyl sulfide is the main contributor to this odor. Fetor hepaticus is frequently a late feature of liver failure, so patients who have dimethyl sulfide blood borne halitosis (and hence underlying dimethylsulfidemia) will likely be profoundly sick. A secondary form of trimethylaminuria is also associated with liver failure, and it has been suggested that trimethylamine is a lesser contributor to the odor of fetor hepaticus.
Medications
Certain medications have been shown to produce dimethylsulfidemia, and consequent blood borne halitosis as a side effect. These medications share the attribute of having dimethyl sulfide as one of their metabolites.
Dimethylsulfoxide
Dimethylsulfoxide is approved for use in interstitial cystitis in the US. It has been investigated for its use in many other conditions, and it is also used as a vehicle for topical administration of anti-inflammatories. A known side effect is a garlic taste in the mouth following cutaneous topical administration.
Cysteamine
Cysteamine is used in the treatment of nephropathic cystinosis.
Suplatast tosilate
Suplatast tosilate is an antiallergenic drug used in asthma. Halitosis caused by blood borne dimethyl sulfide was reported in a patient receiving this therapy.
Management
Dimethylsulfidemia may be a marker of serious systemic disease and so its cause should be further investigated. Liver function tests or assessment of blood methionine levels may appropriate. The treatment is cause specific, for example treatment of underlying liver failure. Very little is known about the newly identified metabolic condition and so the management of this cause is currently unknown.

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