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Dissociated Taste Disorder
Auris' Nasus' Larynx (Tokyo) 13 (Suppl. I), S 17-S 23, 1986
DISSOCIATED TASTE DISORDER Hiroshi TOMITA, M. D. and Yukari HORIKAWA, M. D. Department of Otorhinolaryngology, Nihon University School of Medicine, Tokyo 173, Japan
Primary taste qualities seem to have individual receptor sites. It is theoretically possible for the receptor site of one taste quality to be separately affected. Hypogeusia and ageusia are the most common complaints of patients consulting our clinic for taste disorders. Pantogeusia, heterogeusia and dissociated taste disorders are also often encountered. The purpose of this presentation is to analyze 46 cases of subjective dissociated taste disorders. More than half of the main complaints in such disorders were the loss of sweet taste. We used our filter-paper disc method invented for clinical qualitative and quantitative gustometry by taste examination. We found 12 cases that showed a reduced or absent ability to taste sweet, however, dissociated disorders of other taste qualities could not be found. This result stimulated interest in the hypothesis that the sweet-taste receptor is not a phospholipid but a protein, unlike other taste receptors. We have established a special outpatient clinic designed for the diagnosis and treatment of patients suffering from taste disorders. During the period between 1976 and 1980, we studied 500 patients whose main complaints are shown in Table 1. Spontaneous dysgeusia is experienced by patients who sense a constant bitter taste or other tastes in their mouths even when they are not eating. Dissociated taste disorder is a special symptom occurring when only one or two taste qualities of the four primary tastes are disturbed. The description "disPresented before 8th International Symposium on Olfaction and Taste, Melbourne, Australia, August, 1983 Received for Publication November 10, 1985 Request reprints to: Dr. H. Tomita, Department of Otorhinolaryngology, Nihon University School of Medicine, 30-1 Oyaguchi, Itabashi-ku, Tokyo 173, Japan
sociated taste disorder" is diagnostically applied to denote the main complaint of a patient coming for the first consultation, when it is of great interest to establish whether this phenomenon actually exists as alleged or not. Materials and Methods This report is an attempt to analyze the symptoms of this condition, the main complaint of which is a subjective dissociated disorder of taste. We have studied the patients using our quantitative and qualitative gustometry, using the filter-paper disc (FPD) method (TOMITA, 1982). As shown in the center of the picture in Fig. 1, our filter-paper disc technique is carried out by dividing the four primary tastes into five concentration groups, using a plastic drop bottle for application. As shown in the righthand portion of the picture, each of the primary tastes were dripped onto a filter-paper disc, 5 mm in diameter, and the soaked discs were then placed with tweezers onto the "test points" on the tongue or the soft palate. The patients responded to the exposure by pointing to the appropriate entry on the Taste quality chart to indicate their individual sensation of the taste quality experienced with their mouths open, as shown in the left-hand portion of the picture. As shown in Fig. 2, the test points are located in the anterior and posterior parts of the tongue and the soft palate. Six points were thus tested, according to the different positions of the taste nerves, and differentiated between left and right. For patients with taste disorders, we have adopted the general examination procedures
H. TOMITA and Y. HORIKAWA
S 18
Table 1. Types of taste disorders. * Hypogeusia or ageusia Pantogeusia (spontaneous dysgeusia) Dissociated taste disorder Heterogeusia or parageusia
*
412 (82.4%) 64 (12.8%) 57 (11.4%) 27 ( 5.4%)
There are some overlapping cases.
Fig. 1. The FPD method measuring kit: Disc-Sanwa."
"Taste
)N.gIOSSOPharyng.
----Chorda tympani
Fig. 2. Selecting the location for the measurement of each taste nerve.
indicated in Table 2. 1) Careful questioning: It is of particular importance to inquire with great care into what complaints the patient suffers from at present and into the nature of the remedial measures taken. 2) Extensive examinations of the oral cavity and inspection of the tongue to detect xerostomia, i.e., dryness of the tongue, a furry coat on the tongue, atrophy and keratosis of
Table 2. Routine examination of patients with taste disturbance. 1) Careful questioning: circumstances of onset, appetite, bowel movements, liquor, tobacco, favorite foods, medical history, diseases affected by at present and contents a/the therapy. 2) Inspection of oral cavity and tongue: xerostomia, inflammation, keratosis, atrophy, number of fungiform papillae. 3) Biomicroscopy of the fungiform papillae: form, number, capillary condition. 4) Saliva: pH, electrolytes, minerals, urea nitrogen, uric acid, creatinine. 5) Usual examination of blood and urine: anemia, syphillis, function of liver and kidney, arteriosclerosis, diabetes, albuminuria, hypothyroidism and adrenal cortical insufficiency. 6) Quantitative measurement of trace elements (Zn, Fe, Cu) in serum, hair and urine. 7) Psychoanalysis: CMf, Yatabe-Guilford test, etc. 8) Taste examination: electrogustometry, filter-paper disc method. 9) Biopsy of vallate papillae.
the papillae of the tongue, and other visible abnormalities are carried out. 3) Observation of the fungiform papillae in the anterior part of the tongue under a microscope provides much valuable information about their condition, their number and any abnormalities affecting the capillary vessels. Such findings cannot be obtained by more visual inspection with the naked eye. 4) The pH value, electrolytes, urea nitrogen, creatinine and uric acid of the saliva are measured. 5) Establish abnormalities such as anemia, syphillis, liver and renal injury, arteriosclerosis, hypothyroidism and adrenal cortical insufficiency by examining the patient's blood and urine. 6) Measure the amounts of essential trace metals present in the blood serum, the hair and the urine. These include in particular zinc, iron and copper. 7) For patients in whom psychologicalpsychosomatic factors may be suspected on account of their family environment and from the nature of the onset, CMI and the YatabeGuilford test are used, and a questionnaire
DISSOCIATED TASTE DISORDER
form is completed detailing particulars about masked depression. 8) Gustometry is performed by the electrogustometry and filter-paper disc method that we have already mentioned. 9) On patients who have not responded favorably to the treatment administered, a biopsy is performed on the vallate papillae, and the number of taste buds and morphological changes are studied. The subjects of this investigation were 46 patients due to be examined. By sex, the patients broke down into 20 males and 26 females. Results The results of the investigations can be summed up as illustrated in Table 3. The term "true dissociated taste disorder" has been used when the patient's statement about his own condition is in full agreement with the results of the taste examination, while the term "false dissociated taste disorder" denotes a condition in which the taste dissociation is not borne out by the experimental findings. True dissociated taste disorder was confirmed in 12 patients only with respect to sweetness. No dissociated taste disorder was found for the other types of taste. We will now present some of the most typical cases (Fig. 3). Case I. K.I., age: 76, sex: male. The patient noted the complete absence of sweet taste sensation for about 2 weeks prior to the examination. No particular change was felt in the sensation of the other tastes. No habitual medication was being taken. As can be seen in Fig. 3, Case I, a filter-paper disc test was performed at the patient's first consultation. The results of this test revealed that, in all three nerve regions, there had been a deterioration of the taste threshold sensitivity for sweetness only. It was realized that the taste threshold sensitivity in the areas of the greater petrosal nerves was extremely good with respect to tastes other than sweetness. Examination showed that the zinc level in the
S 19
Table 3. Analysis of subjective dissociated taste disorders (46 cases). 1)
2) 3) 4) 5)
6)
7)
8)
Hypo- or ageusia of sweet taste only True dissociated taste disorders False dissociated taste disorders Hypo- or ageusia of salty taste only True D T.D. Hypo- or ageusia sour taste only True D.T.D. Hypo- or ageusia of bitter taste only True D.T.D. Hypo- or ageusia of sweet and salty taste True D.T.D. Hypo- or ageusia of salty and sour taste True D.T.D. Hypo- or ageusia of salty and bitter taste True D.T.D. Hypo- or ageusia except sweet taste True D.T.D.
26 cases 12 14 10 0 4 0 2 0
0 1 0
0 1 0
blood serum was low and that the serum iron had risen. It was assumed that the zinc deficiency had led to the taste disorder, and thus zinc sulfate treatment by oral administration was prescribed. The patient was almost completely cured of the taste disturbance after about 2 weeks. Case 2. C.H., age: 67, sex: female. A month and a half before the examination, the patient became aware of a lack of sweet taste sensation when eating sweets and stated that no change had occurred in her ability to taste sour foods, for example, lemons. A filter-paper disc test was performed. The results are as shown in Fig. 3, Case 2. During the first consultation, the patient was examined when it became clear that the threshold sensitivity to sweetness in the areas of the chorda tympani and the greater petrosal nerve had greatly deteriorated as compared with their threshold sensitivity to the other three tastes. Examination of the patient's blood serum revealed only two positive pieces of evidence: zinc deficiency and increased copper levels. It was concluded that the zinc deficiency had led to the taste disorder. Thus, zinc sulfate was prescribed for internal administration.
H. TOMITA and Y. HORIKAWA
S 20
Case 1. K.1. 76y M idiopathic hypozincemia
g
(1977.8 .30) c 0
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2
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~ 3
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(1977 . 11.18)
N Zn
67> 96 167t
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.
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c. F.
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9' 107
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Case 2. C.H. 67y F idiopathic hypozincemia (1977 . 5 . 23)
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67",
Cu
US, 114
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.
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-'
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5
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70 111 107
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~
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5
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o
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(1979 . 3.22)
~ 3
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'.
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Case 3. S.Y. 48y F inducement by drug c
91
~ N.D.
S
.g 2
(1977 . 12 . 19) Zn
T : tartaric acid
of chorda tymp.
Fig. 3.
N
T
Q
1
(1979 . 3 .29)
~9
3 5
N.D.
N
T
Q
(a-mercaptopropionyl glycine)
2 4
S
t "",/
' ......
'x___ ... ___
5
N T
Q : quinine HCI
~
Q
N.D :not detective
~·~ : Sllo..oph.ryg.N.
. ··«: gr. petro N.
Typical cases of true DTD with respect to sweetness.
Two months later, the patient had recovered her sweet sensation by an average of two ranks or even more, and, after 7 months of treatment, the patient was completely cured. Case 3. S.Y. , age: 48, sex: female. Two weeks prior to the examination, the patient realized that, although she was eating sweet beans, she had no sensation of sweetness. She had undergone treatment for liver spots and, thus, had taken alpha-mercaptopropionyl glycine and vitamin C. A filterpaper disc test was performed on the patient, and the results and observations are as shown in Fig. 3, Case 3. During her first consultation, dissociated taste disorder was detected
in the areas of the chorda tympani and the glossopharyngeal nerves only with respect to sweet taste. It was concluded that, prior to the onset, the patient had developed a druginduced taste disturbance associated with the ingestion of alpha-mercaptopropionyl glycine. This drug has a strong zinc chelating action. Therefore, medication was stopped immediately. The zinc level in the patient's blood serum was in the lower range of normal values, but zinc administration was not prescribed, and the treatment attempted was limited to the discontinuation of alphamercaptopropionyl glycine medication. The filter-paper disc test performed a week later
DISSOCIATED TASTE DISORDER
showed a rapid recovery of the patient's threshold sensitivity to sweetness. The 12 patients found to suffer from true dissociated taste disturbance were tested for clinical characteristics. Most patients were in their 40s at the time of onset and fourfifths of them were females. These two facts were prominent in the pattern of taste disorder as a whole. Differentiation between the sexes showed that female patients outnumbered males by a factor of two. Seen on a general scale, there is a predominance of female patients with taste disorders, with a male-tofemale ratio of 2 to 3. In terms of the cause of the disturbance, idiopathic genesis of the disorder was by far more widespread, affecting eight patients. Of these, seven showed zinc deficiency in the serum. The next causal factors were induceTable 4. Causes of true dissociated taste disorder: Comparison with total cases of taste disturbance. Causes Idiopathic Drugs Influenza-like disease Systemic disease Cerebral disease Local disturbance Mental Others
True dissociated taste disorder
Total cases of taste disturbance*
8 (67%) 3 (25%) 1(8%)
186(37 %) 143 (29%)** 60 (12 %) 44 ( 36 ( 32 ( 8( 20 (
0 0 0 0 0
9 %) 7%) 6 %) 2%) 4 %)
* 500 cases in the period from 1976 to 1980. ** There are some overlapping causes.
S 21
ment by drugs, affecting three patients, and influenza-like diseases, affecting one. The right-hand part of Table 4 gives a breakdown of the frequency of the causal factors in the genesis of taste disorders as a whole. Comparison between the causal factors indicated makes it quite clear that none of the patients with true dissociated taste disorder had acquired this condition as a result of systemic diseases, cerebral lesions, local disorders or mental-psychological problems. The incidence of idiopathic genesis in true dissociated taste disorders is very high compared with taste disturbances in general, and there is a significant difference between both disorders, with a level of significance of 5 %. Table 5 shows the levels of trace elements and electrolytes in the blood serum and relates these to the incidence of true dissociated taste disorder. The right-hand portion of the table gives the incidence of abnormal cases among the total number of cases with taste disorder, but there is no significant difference between the two. We have studied whether or not the development of true dissociated taste disorder is typically related to the occurrence of certain inorganic and/or organic substances in the saliva. On the right-hand side of Table 6, we have chosen a random sample of 100 patients from general cases of taste disorders and investigated the incidence of abnormal cases among this sample. As can be seen, no significant difference has been found.
Table 5. Trace metals and electrolytes in serum of true dissociated taste disorder: Comparison with total cases of taste disturbance. True dissociated taste disorder
Zinc Copper Iron Calcium Magnesium Phosphorus
*
Increase
Reduction
0 1/12 (8 %) 1/12 (8 %) 0 0 0
8/12 (67 %) 0 1/12 (8 %) 0 0 0
Cases of abnormal level/total cases.
Total cases of taste disturbance Increase
Reduction
o
216/415*( 52 %) 3/413 (0.7 %) 143/433 ( 33 %) 27/416 ( 6%) 28/401 ( 7 %) 10/399 ( 3 %)
120/413 ( 29 %) 12/433 ( 3 %) 2/416 (0.5%) 4/401 ( 1 %)
o
S 22
H. TOMITA and Y. HORIKAWA
Table 6. Salivary components of true dissociated taste disorder: Comparison with total cases of taste disturbance. True dissociated taste disorder Increase Reduction Sodium Potassium Calcium Magnesium Phosphorus Urea nitrogen Creatinine Uric acid
100 cases with taste disturbance'" Increase
( %)
(%)
(%)
10
30 20 0 10 10 50 80 10
12 17 62 21 23 34 0
30 70 40 20 10 0 0
Reduction (%)
32 38 9 19 7 34 68 31
'" Chosen at random from total cases.
Discussion Primary taste qualities seem to have individual receptor sites. It is theoretically possible for the receptor site of one taste quality to be separately affected. HENKIN and SHALLENBERGER (1970) reported on two patients suffering from congenital idiopathic hypoparathyroidism. Neither could recognize the taste of any sweet substances; however, they indicated normal recognition of other taste qualities. HASEGAWA et al. (1979) also reported on two patients with idiopathic dissociated taste disorder only with respect to sweetness. The question is why dissociated taste disorder affecting only the sensation of sweetness occurs? Sweetness differs from the other three primary tastes in that it is brought about by a protein acting as a receptor. This implies that the sensation of sweetness is perceived as a result of the sweet-tasting substance combining with the sweet-sensitive protein. HIJI (1975) has found that, when applying a proteolytic enzyme to the tongue surface of a human and a rat, only the responsiveness to sweetness is selectively suppressed, without affecting those to other kinds of taste stimuli. This phenomenon is interpreted in terms of the structural changes produced in the makeup of the sweet-sensitive receptor protein as a
Table 7. Hypothesis on occurrence of the dissociated taste disorder of sweetness only. Taste receptor site (microvilli of taste cell)
i
I
Existence of zinc and zinc enzymes
->
Sweet-tasting receptor II . Protem Protein
s~nthesis i
.
Main role of zmc
Synthesis of the receptor protein may be depressed by zinc deficiency.
result of the action of pronase. In patients suffering from true dissociated taste disorders, the predominant cause of the condition is zinc deficiency. When zinc is not available in adequate quantities, the synthesis of the protein at the sweet-sensitive receptor site can no longer be achieved smoothly, and this may lead to the development of the complaint (Table 7). Summary Dissociated taste disorder is a special symptom occurring when only one or two taste qualities of the four primary taste are disturbed. Eleven % of all cases of taste disorders complain of this symptom. The subjects of this investigation were 46 patients due to be examined. We used our filter-paper disc method invented for clinical qualitative and quantitative gustometry by taste examination. True dissociated taste disorder was confirmed in 12 patients only with respect to sweetness. No dissociated taste disorder was found for the other types of taste. Sweetness differs from the other three primary tastes in that it is brought about by a protein acting as a receptor. In patients suffering from true dissociated taste disorders, the predominant cause of the condition is zinc deficiency. When zinc is not available in adequate quantities, the synthesis of the protein at the sweet-sensitive receptor site can no longer be achieved smoothly, and this may lead to the development of the complaint.
DISSOCIATED TASTE DISORDER
References HASEGAWA, A., OHIRA, H., and NISHIMURA, K.: Two cases of ageusia of sweetness. lpn. l. Stomatol. Soc. 28: 42-47, 1979. HENKIN, R. I., and SHALLENBERGER, R. S.: Aglycogeusia: The inability to recognize sweetness and its possible molecular basis. Nature 227: 965966, 1970.
S 23
HIJI, Y.: Selective elimination of taste responses to sugars by proteolytic enzymes. Nature 256: 427429, 1975. TOMITA, H.: Methods in taste examination. In Proc. XIIth ORL World Congr., Budapest, Hungary 1981 (Surjan, L., and Bodo, Gy., eds.), p. 627, Excerpta Medica, Amsterdam-Oxford-Princeton, 1982.
DISSOCIATED TASTE DISORDER Hiroshi TOMITA, M. D. and Yukari HORIKAWA, M. D. Department of Otorhinolaryngology, Nihon University School of Medicine, Tokyo 173, Japan
Primary taste qualities seem to have individual receptor sites. It is theoretically possible for the receptor site of one taste quality to be separately affected. Hypogeusia and ageusia are the most common complaints of patients consulting our clinic for taste disorders. Pantogeusia, heterogeusia and dissociated taste disorders are also often encountered. The purpose of this presentation is to analyze 46 cases of subjective dissociated taste disorders. More than half of the main complaints in such disorders were the loss of sweet taste. We used our filter-paper disc method invented for clinical qualitative and quantitative gustometry by taste examination. We found 12 cases that showed a reduced or absent ability to taste sweet, however, dissociated disorders of other taste qualities could not be found. This result stimulated interest in the hypothesis that the sweet-taste receptor is not a phospholipid but a protein, unlike other taste receptors. We have established a special outpatient clinic designed for the diagnosis and treatment of patients suffering from taste disorders. During the period between 1976 and 1980, we studied 500 patients whose main complaints are shown in Table 1. Spontaneous dysgeusia is experienced by patients who sense a constant bitter taste or other tastes in their mouths even when they are not eating. Dissociated taste disorder is a special symptom occurring when only one or two taste qualities of the four primary tastes are disturbed. The description "disPresented before 8th International Symposium on Olfaction and Taste, Melbourne, Australia, August, 1983 Received for Publication November 10, 1985 Request reprints to: Dr. H. Tomita, Department of Otorhinolaryngology, Nihon University School of Medicine, 30-1 Oyaguchi, Itabashi-ku, Tokyo 173, Japan
sociated taste disorder" is diagnostically applied to denote the main complaint of a patient coming for the first consultation, when it is of great interest to establish whether this phenomenon actually exists as alleged or not. Materials and Methods This report is an attempt to analyze the symptoms of this condition, the main complaint of which is a subjective dissociated disorder of taste. We have studied the patients using our quantitative and qualitative gustometry, using the filter-paper disc (FPD) method (TOMITA, 1982). As shown in the center of the picture in Fig. 1, our filter-paper disc technique is carried out by dividing the four primary tastes into five concentration groups, using a plastic drop bottle for application. As shown in the righthand portion of the picture, each of the primary tastes were dripped onto a filter-paper disc, 5 mm in diameter, and the soaked discs were then placed with tweezers onto the "test points" on the tongue or the soft palate. The patients responded to the exposure by pointing to the appropriate entry on the Taste quality chart to indicate their individual sensation of the taste quality experienced with their mouths open, as shown in the left-hand portion of the picture. As shown in Fig. 2, the test points are located in the anterior and posterior parts of the tongue and the soft palate. Six points were thus tested, according to the different positions of the taste nerves, and differentiated between left and right. For patients with taste disorders, we have adopted the general examination procedures
H. TOMITA and Y. HORIKAWA
S 18
Table 1. Types of taste disorders. * Hypogeusia or ageusia Pantogeusia (spontaneous dysgeusia) Dissociated taste disorder Heterogeusia or parageusia
*
412 (82.4%) 64 (12.8%) 57 (11.4%) 27 ( 5.4%)
There are some overlapping cases.
Fig. 1. The FPD method measuring kit: Disc-Sanwa."
"Taste
)N.gIOSSOPharyng.
----Chorda tympani
Fig. 2. Selecting the location for the measurement of each taste nerve.
indicated in Table 2. 1) Careful questioning: It is of particular importance to inquire with great care into what complaints the patient suffers from at present and into the nature of the remedial measures taken. 2) Extensive examinations of the oral cavity and inspection of the tongue to detect xerostomia, i.e., dryness of the tongue, a furry coat on the tongue, atrophy and keratosis of
Table 2. Routine examination of patients with taste disturbance. 1) Careful questioning: circumstances of onset, appetite, bowel movements, liquor, tobacco, favorite foods, medical history, diseases affected by at present and contents a/the therapy. 2) Inspection of oral cavity and tongue: xerostomia, inflammation, keratosis, atrophy, number of fungiform papillae. 3) Biomicroscopy of the fungiform papillae: form, number, capillary condition. 4) Saliva: pH, electrolytes, minerals, urea nitrogen, uric acid, creatinine. 5) Usual examination of blood and urine: anemia, syphillis, function of liver and kidney, arteriosclerosis, diabetes, albuminuria, hypothyroidism and adrenal cortical insufficiency. 6) Quantitative measurement of trace elements (Zn, Fe, Cu) in serum, hair and urine. 7) Psychoanalysis: CMf, Yatabe-Guilford test, etc. 8) Taste examination: electrogustometry, filter-paper disc method. 9) Biopsy of vallate papillae.
the papillae of the tongue, and other visible abnormalities are carried out. 3) Observation of the fungiform papillae in the anterior part of the tongue under a microscope provides much valuable information about their condition, their number and any abnormalities affecting the capillary vessels. Such findings cannot be obtained by more visual inspection with the naked eye. 4) The pH value, electrolytes, urea nitrogen, creatinine and uric acid of the saliva are measured. 5) Establish abnormalities such as anemia, syphillis, liver and renal injury, arteriosclerosis, hypothyroidism and adrenal cortical insufficiency by examining the patient's blood and urine. 6) Measure the amounts of essential trace metals present in the blood serum, the hair and the urine. These include in particular zinc, iron and copper. 7) For patients in whom psychologicalpsychosomatic factors may be suspected on account of their family environment and from the nature of the onset, CMI and the YatabeGuilford test are used, and a questionnaire
DISSOCIATED TASTE DISORDER
form is completed detailing particulars about masked depression. 8) Gustometry is performed by the electrogustometry and filter-paper disc method that we have already mentioned. 9) On patients who have not responded favorably to the treatment administered, a biopsy is performed on the vallate papillae, and the number of taste buds and morphological changes are studied. The subjects of this investigation were 46 patients due to be examined. By sex, the patients broke down into 20 males and 26 females. Results The results of the investigations can be summed up as illustrated in Table 3. The term "true dissociated taste disorder" has been used when the patient's statement about his own condition is in full agreement with the results of the taste examination, while the term "false dissociated taste disorder" denotes a condition in which the taste dissociation is not borne out by the experimental findings. True dissociated taste disorder was confirmed in 12 patients only with respect to sweetness. No dissociated taste disorder was found for the other types of taste. We will now present some of the most typical cases (Fig. 3). Case I. K.I., age: 76, sex: male. The patient noted the complete absence of sweet taste sensation for about 2 weeks prior to the examination. No particular change was felt in the sensation of the other tastes. No habitual medication was being taken. As can be seen in Fig. 3, Case I, a filter-paper disc test was performed at the patient's first consultation. The results of this test revealed that, in all three nerve regions, there had been a deterioration of the taste threshold sensitivity for sweetness only. It was realized that the taste threshold sensitivity in the areas of the greater petrosal nerves was extremely good with respect to tastes other than sweetness. Examination showed that the zinc level in the
S 19
Table 3. Analysis of subjective dissociated taste disorders (46 cases). 1)
2) 3) 4) 5)
6)
7)
8)
Hypo- or ageusia of sweet taste only True dissociated taste disorders False dissociated taste disorders Hypo- or ageusia of salty taste only True D T.D. Hypo- or ageusia sour taste only True D.T.D. Hypo- or ageusia of bitter taste only True D.T.D. Hypo- or ageusia of sweet and salty taste True D.T.D. Hypo- or ageusia of salty and sour taste True D.T.D. Hypo- or ageusia of salty and bitter taste True D.T.D. Hypo- or ageusia except sweet taste True D.T.D.
26 cases 12 14 10 0 4 0 2 0
0 1 0
0 1 0
blood serum was low and that the serum iron had risen. It was assumed that the zinc deficiency had led to the taste disorder, and thus zinc sulfate treatment by oral administration was prescribed. The patient was almost completely cured of the taste disturbance after about 2 weeks. Case 2. C.H., age: 67, sex: female. A month and a half before the examination, the patient became aware of a lack of sweet taste sensation when eating sweets and stated that no change had occurred in her ability to taste sour foods, for example, lemons. A filter-paper disc test was performed. The results are as shown in Fig. 3, Case 2. During the first consultation, the patient was examined when it became clear that the threshold sensitivity to sweetness in the areas of the chorda tympani and the greater petrosal nerve had greatly deteriorated as compared with their threshold sensitivity to the other three tastes. Examination of the patient's blood serum revealed only two positive pieces of evidence: zinc deficiency and increased copper levels. It was concluded that the zinc deficiency had led to the taste disorder. Thus, zinc sulfate was prescribed for internal administration.
H. TOMITA and Y. HORIKAWA
S 20
Case 1. K.1. 76y M idiopathic hypozincemia
g
(1977.8 .30) c 0
';
2
c.
~ 3
F.
•"c
(1977 . 11.18)
N Zn
67> 96 167t
"0
2 ~/'
.g
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• ,,-
1E
0
0
4
5
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N.D.
~
S
T
N
" ...--.,./ .- '"
>,' /- .... .. '
t
N T
S
Q
.
Zn
c. F.
,.
9' 107
Q
Case 2. C.H. 67y F idiopathic hypozincemia (1977 . 5 . 23)
c
i:r~ '/~/ 8
~ Zn
67",
Cu
US, 114
Fe
1
.
"02 c
.g
3 "4 ]- 5
5 • /
N.D.
(1977 . 8.5 )
A t .
-'
N T
·•
g4
.3
5
N.D.
'
'
\
{::' 'l_~ _~_.« S
N T
S :auger
S
Zn Cu
Fe
70 111 107
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~
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~0
Q
N: Nit
~:ar..
~
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5
t
o
Q
(1979 . 3.22)
~ 3
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'.
"! N.D.
Case 3. S.Y. 48y F inducement by drug c
91
~ N.D.
S
.g 2
(1977 . 12 . 19) Zn
T : tartaric acid
of chorda tymp.
Fig. 3.
N
T
Q
1
(1979 . 3 .29)
~9
3 5
N.D.
N
T
Q
(a-mercaptopropionyl glycine)
2 4
S
t "",/
' ......
'x___ ... ___
5
N T
Q : quinine HCI
~
Q
N.D :not detective
~·~ : Sllo..oph.ryg.N.
. ··«: gr. petro N.
Typical cases of true DTD with respect to sweetness.
Two months later, the patient had recovered her sweet sensation by an average of two ranks or even more, and, after 7 months of treatment, the patient was completely cured. Case 3. S.Y. , age: 48, sex: female. Two weeks prior to the examination, the patient realized that, although she was eating sweet beans, she had no sensation of sweetness. She had undergone treatment for liver spots and, thus, had taken alpha-mercaptopropionyl glycine and vitamin C. A filterpaper disc test was performed on the patient, and the results and observations are as shown in Fig. 3, Case 3. During her first consultation, dissociated taste disorder was detected
in the areas of the chorda tympani and the glossopharyngeal nerves only with respect to sweet taste. It was concluded that, prior to the onset, the patient had developed a druginduced taste disturbance associated with the ingestion of alpha-mercaptopropionyl glycine. This drug has a strong zinc chelating action. Therefore, medication was stopped immediately. The zinc level in the patient's blood serum was in the lower range of normal values, but zinc administration was not prescribed, and the treatment attempted was limited to the discontinuation of alphamercaptopropionyl glycine medication. The filter-paper disc test performed a week later
DISSOCIATED TASTE DISORDER
showed a rapid recovery of the patient's threshold sensitivity to sweetness. The 12 patients found to suffer from true dissociated taste disturbance were tested for clinical characteristics. Most patients were in their 40s at the time of onset and fourfifths of them were females. These two facts were prominent in the pattern of taste disorder as a whole. Differentiation between the sexes showed that female patients outnumbered males by a factor of two. Seen on a general scale, there is a predominance of female patients with taste disorders, with a male-tofemale ratio of 2 to 3. In terms of the cause of the disturbance, idiopathic genesis of the disorder was by far more widespread, affecting eight patients. Of these, seven showed zinc deficiency in the serum. The next causal factors were induceTable 4. Causes of true dissociated taste disorder: Comparison with total cases of taste disturbance. Causes Idiopathic Drugs Influenza-like disease Systemic disease Cerebral disease Local disturbance Mental Others
True dissociated taste disorder
Total cases of taste disturbance*
8 (67%) 3 (25%) 1(8%)
186(37 %) 143 (29%)** 60 (12 %) 44 ( 36 ( 32 ( 8( 20 (
0 0 0 0 0
9 %) 7%) 6 %) 2%) 4 %)
* 500 cases in the period from 1976 to 1980. ** There are some overlapping causes.
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ment by drugs, affecting three patients, and influenza-like diseases, affecting one. The right-hand part of Table 4 gives a breakdown of the frequency of the causal factors in the genesis of taste disorders as a whole. Comparison between the causal factors indicated makes it quite clear that none of the patients with true dissociated taste disorder had acquired this condition as a result of systemic diseases, cerebral lesions, local disorders or mental-psychological problems. The incidence of idiopathic genesis in true dissociated taste disorders is very high compared with taste disturbances in general, and there is a significant difference between both disorders, with a level of significance of 5 %. Table 5 shows the levels of trace elements and electrolytes in the blood serum and relates these to the incidence of true dissociated taste disorder. The right-hand portion of the table gives the incidence of abnormal cases among the total number of cases with taste disorder, but there is no significant difference between the two. We have studied whether or not the development of true dissociated taste disorder is typically related to the occurrence of certain inorganic and/or organic substances in the saliva. On the right-hand side of Table 6, we have chosen a random sample of 100 patients from general cases of taste disorders and investigated the incidence of abnormal cases among this sample. As can be seen, no significant difference has been found.
Table 5. Trace metals and electrolytes in serum of true dissociated taste disorder: Comparison with total cases of taste disturbance. True dissociated taste disorder
Zinc Copper Iron Calcium Magnesium Phosphorus
*
Increase
Reduction
0 1/12 (8 %) 1/12 (8 %) 0 0 0
8/12 (67 %) 0 1/12 (8 %) 0 0 0
Cases of abnormal level/total cases.
Total cases of taste disturbance Increase
Reduction
o
216/415*( 52 %) 3/413 (0.7 %) 143/433 ( 33 %) 27/416 ( 6%) 28/401 ( 7 %) 10/399 ( 3 %)
120/413 ( 29 %) 12/433 ( 3 %) 2/416 (0.5%) 4/401 ( 1 %)
o
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H. TOMITA and Y. HORIKAWA
Table 6. Salivary components of true dissociated taste disorder: Comparison with total cases of taste disturbance. True dissociated taste disorder Increase Reduction Sodium Potassium Calcium Magnesium Phosphorus Urea nitrogen Creatinine Uric acid
100 cases with taste disturbance'" Increase
( %)
(%)
(%)
10
30 20 0 10 10 50 80 10
12 17 62 21 23 34 0
30 70 40 20 10 0 0
Reduction (%)
32 38 9 19 7 34 68 31
'" Chosen at random from total cases.
Discussion Primary taste qualities seem to have individual receptor sites. It is theoretically possible for the receptor site of one taste quality to be separately affected. HENKIN and SHALLENBERGER (1970) reported on two patients suffering from congenital idiopathic hypoparathyroidism. Neither could recognize the taste of any sweet substances; however, they indicated normal recognition of other taste qualities. HASEGAWA et al. (1979) also reported on two patients with idiopathic dissociated taste disorder only with respect to sweetness. The question is why dissociated taste disorder affecting only the sensation of sweetness occurs? Sweetness differs from the other three primary tastes in that it is brought about by a protein acting as a receptor. This implies that the sensation of sweetness is perceived as a result of the sweet-tasting substance combining with the sweet-sensitive protein. HIJI (1975) has found that, when applying a proteolytic enzyme to the tongue surface of a human and a rat, only the responsiveness to sweetness is selectively suppressed, without affecting those to other kinds of taste stimuli. This phenomenon is interpreted in terms of the structural changes produced in the makeup of the sweet-sensitive receptor protein as a
Table 7. Hypothesis on occurrence of the dissociated taste disorder of sweetness only. Taste receptor site (microvilli of taste cell)
i
I
Existence of zinc and zinc enzymes
->
Sweet-tasting receptor II . Protem Protein
s~nthesis i
.
Main role of zmc
Synthesis of the receptor protein may be depressed by zinc deficiency.
result of the action of pronase. In patients suffering from true dissociated taste disorders, the predominant cause of the condition is zinc deficiency. When zinc is not available in adequate quantities, the synthesis of the protein at the sweet-sensitive receptor site can no longer be achieved smoothly, and this may lead to the development of the complaint (Table 7). Summary Dissociated taste disorder is a special symptom occurring when only one or two taste qualities of the four primary taste are disturbed. Eleven % of all cases of taste disorders complain of this symptom. The subjects of this investigation were 46 patients due to be examined. We used our filter-paper disc method invented for clinical qualitative and quantitative gustometry by taste examination. True dissociated taste disorder was confirmed in 12 patients only with respect to sweetness. No dissociated taste disorder was found for the other types of taste. Sweetness differs from the other three primary tastes in that it is brought about by a protein acting as a receptor. In patients suffering from true dissociated taste disorders, the predominant cause of the condition is zinc deficiency. When zinc is not available in adequate quantities, the synthesis of the protein at the sweet-sensitive receptor site can no longer be achieved smoothly, and this may lead to the development of the complaint.
DISSOCIATED TASTE DISORDER
References HASEGAWA, A., OHIRA, H., and NISHIMURA, K.: Two cases of ageusia of sweetness. lpn. l. Stomatol. Soc. 28: 42-47, 1979. HENKIN, R. I., and SHALLENBERGER, R. S.: Aglycogeusia: The inability to recognize sweetness and its possible molecular basis. Nature 227: 965966, 1970.
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HIJI, Y.: Selective elimination of taste responses to sugars by proteolytic enzymes. Nature 256: 427429, 1975. TOMITA, H.: Methods in taste examination. In Proc. XIIth ORL World Congr., Budapest, Hungary 1981 (Surjan, L., and Bodo, Gy., eds.), p. 627, Excerpta Medica, Amsterdam-Oxford-Princeton, 1982.