ПЕДИАТРИЯ
102
Rixsiyev U.Sh., Rakhmankulova S.A.
The problem of vitiligo is currently one of the
most important and difficult to cure in dermatology,
especially in our region, where there is still inadequate
attitude of others to these patients. Along with the
successes achieved in the study of this disease there are
many controversial and unresolved issues concerning
its etiology, pathogenesis and treatment.
Vitiligo is currently considered as a
multifactorial disease of the organism [2-10]. When
studying the etiology and pathogenesis of vitiligo, much
attention is paid to the study of metabolic processes in
the div. Many have found in this dermatosis changes
in mineral, carbohydrate, lipid, vitamin and other types
of metabolism [2-10]. According to literature sources,
amino acid metabolism in vitiligo patients is disturbed,
but these data are controversial, in addition, they are
obtained with the help of low-informative laboratory
methods of research [3,5,9]. In this regard, the study of
amino acids metabolism, which are the main structural
elements of protein molecule, including melanocytes,
melanin, is of certain interest. The biochemical essence
of this phenomenon is still unclear. But about the
reasons of melanogenesis disturbance in vitiligo there
are controversial judgments of researchers [1,8]. If we
take into account that the ancestor of melanin is
tyrosine, and such amino acids as phenylalanine,
arginine, histidine, methionine are directly related to
melanin metabolism, then the study of amino acid
spectrum of blood in vitiligo patients is of certain
interest.
Materials and methods of the study
The amino acid spectrum of blood was studied
using high-performance liquid chromatography
(HPLC) according to the Kochen method. Free amino
acids were isolated from biological fluids by
precipitation with a 20% solution of TCUK. During
precipitation of proteins with TCUK, acidic peptides
remained in solution and were the last to leave the
column during amino acid analysis. Therefore, they did
not screen for the identification of free amino acids.
To solve the set goal, we analyzed 18 amino
acids in serum of 36 children with vitiligo patients. Of
them, 7 had limited, 14 - disseminated, 6 - generalized
forms of vitiligo, and 5 had Seton's disease. The control
group consisted of 12 healthy children of similar age.
Results
Analysis of the obtained data showed statistically
reliable increase in concentration of all studied amino
acids, except phenylalanine (Table 1). From the studied
18 amino acids, the biggest discrepancy was stated in
the indices of cysteine, where its concentration in blood
serum was 7.4 times more in comparison with the
control group (in the control group 29.32±1.78; in the
examined patients 218.0±11.27). Concentration of
histidine, glutamic and asparagic acids was almost 3
times higher (318,41±18,53-922,5±14,48; 79,75±3,68
233,31±5,63; 76,56±4,08-223,295±9,43 in patients and
healthy subjects, respectively, at P<0,001). Significant
increase was registered in the indices of isoleucine,
valine, threonine, argenine, proline, lysine, where their
quantity exceeded the corresponding indices of the
control group in 2,1-2,5 times (P<0,001). In the same
reliability (P<0,001), serine, leucine, tyrosine and
tryptophan concentrations were increased in blood
serum. The amounts of methionine and alanine in the
examined patients were also statistically significantly
(P<0.05) different from those of the control group
(87.98± 3.21-97.5± 4.05; 110.4±5.58137.76±4.06,
respectively). Among the 18 amino acids studied, only
phenylalanine
concentration
was
statistically
significantly (P<0.05) lower than in healthy children
(53.45±2.78; 45.51±2.85 in sick and healthy children,
respectively).
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THE STATE OF BLOOD AMINO ACID SPECTRUM IN CHILDREN WITH VITILIGO
Tashkent pediatric medical institute
103
Table 1
Amino acid spectrum of blood in children with vitiligo before treatment
Along with hyperaminoacidemia, the change of
ratios between separate amino acids was revealed:
phenylalanine/tyrosine coefficients were reduced (in
healthy people - 0,4; in vitiligo patients - 0,18),
histidine/glutamic acid (in healthy people - 4,2; in
vitiligo patients - 4,0) and serine/glycine (in healthy
people - 1,6; in vitiligo patients - 1,2). Violation of
coefficients asparagic acid/alanine (in healthy people -
0,7; in vitiligo patients - 1,7), glutamic acid/proline (in
healthy people - 0,3; in vitiligo patients - 0,48) was
established, that indicates the expressed violation of
amino acids metabolism.
When comparing the percentage ratio of amino
acids in vitiligo patients compared to healthy children,
a certain pattern of changes in the amino acid spectrum
was found: against the background of a decrease in
phenylalanine, a sharp increase in cysteine, histidine,
asparagine acid, glycine, less - methionine, lysine,
tyrosine, tryptophan and serine. It should be noted that
this pattern of changes in children with vitiligo does not
differ from those in secondary metabolic disorders
caused by chronic diseases of the digestive system.
Taking into account the above-mentioned, we
analyzed the obtained data of amino acid spectrum
depending on the clinical forms of the disease (Table 2).
As can be seen from the table, the greatest discrepancies
in amino acids indices were found in patients with
generalized form of the disease,
Aminoacids
Control group (p-12) Patients with vitiligo
(п-36)
Р
How many times
increased or
decreased
Methionine
87,98± 3,21
97,5± 4,05
Р <0,001
<1,11
Glutamic acid
76,56±4,08
223,295±9,43
Р <0,001
<2,92
Isoleucine
63,45±4,45
139,119±7,71
Р <0,001
<2,2
Threonine
71,65±5,76
182,2211±4,55
Р <0,001
<2,5
Serine
93,14±4,8
181,03±3,69
Р <0,001
<1,9
Glycine
59,85±2,32
152,5±5,32
Р <0,001
<2,6
Phenylalanine
53,45±2,78
45,51±2,85
Р < 0,05
>0,85
Leucine
77,91±3,35
146,65±3,81
Р <0,001
<1,88
Valine
103,76±6,08
229,08±4,97
Р <0,001
<2,2
Alanine
110,4±5,58
137,76±4,06
Р <0,05
<1,3
Argenine
303,32±12,45
781,39±11,87
Р <0,001
<2,6
Proline
222,78±13,67
468,3±9,58
Р <0,001
<2,1
Cysteine
29,32±1,78
218,0±11,27
Р <0,001
<7,4
Asparg. acid
79,75±3,68
233,31±5,63
Р <0,001
<2,9
Histidine
318,41±18,53
922,5±14,48
Р <0,001
<2,9
Lysine
43,62±2,61
92,502±2,88
Р <0,001
<2,1
Tyrosine
129,36±14,58
245,69±9,94
Р <0,001
<1,9
Tryptophan
66,95±3,45
112,767±4,59
Р <0,001
<1,7
Note: P- reliability in comparison with the data of the control group.
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ПЕДИАТРИЯ
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especially in tyrosine indices, which in comparison with
the control group were increased almost 2 times
(129,36±14,58; 245,9±10,75), in contrast to patients
with limited form - 1,4 times (at P < 0,001). Indices of
cysteine in patients with generalized form of vitiligo in
comparison with the control group were 7,5 times
higher, and in patients with localized form - 2,3 times
higher. As can be seen from the data in Table 2, the
same trend was observed in the indicators of argenin,
histidine, tryptophan, glutamic acid, threonine, to a
lesser extent methionine.
Note: * marked reliability of the difference and indicators equal to P< 0.05; ** P< 0.001 when comparing with the control group.
Table 2
Amino acid spectrum of blood in children with vitiligo depending on the clinical form of the disease of the
clinical form of the disease
№ Aminoacids
Control group
(п-12)
Clinical forms of vitiligo
Limited (п-7)
Disseminated (п-
14)
Generalized
(п-6)
Disease
Sutton's (п-5)
1
Methionine
87,98± 3,21 91,69±3,97
93,54±2,95
97,5±3,17*
89,20±2,44
2
Glutamic acid
76,56±4,08
102,7±5,42** 198,44±7,47**
223,3±5,74**
85,67±3,18
3
Isoleucine
63,45±4,45
84,48±3,71*
112,92±4,21**
139,2±8,15**
71,14±4,36
4
Threonine
71,65±5,76
94,42±5,24*
137,65±6,55**
182,2±7,36**
91,9±4,42*
5
Serine
93,14±4,8
116,02±6,68** 146,81±6,08**
181,1±7,44** 106,72±5,39*
6
Glycine
59,85±2,32
78,68±2,84*
129,04±3,67**
152,5±5,87**
63,54±3,27
7
Phenylalanine
53,45±2,78
51,05±1,89
47,7±2,88*
45,5±3,17*
52,06±2,88
8
Leucine
77,91±3,35
94,37±4,06*
123,26±6,24**
146,7±11,08**
88,36±2,16*
9
Valine
103,76±6,08 141,83±5,87** 188,43±6,13**
229,1±8,37** 122,87±4,48*
10 Alanine
110,4±5,58
114,85±6,47
124,07±5,38*
137,76±6,79**
115,05±5,11
11 Argenine
303,32±12,45 450,6±15,49** 579,51±12,6**
781,39±14,8** 378,45±13,58*
12 Proline
222,78±13,67 278,07±11,8** 336,89±11,29** 468,3±12,83** 244,62±8,39*
13 Cysteine
29,32±1,78
94,58±4,29** 168,77±6,53**
218±7,16**
58,09±3,37**
14 Asparg. acid
79,75±3,68
122,36±4,15** 183,49±7,74**
233,3±13,22** 106,38±5,22**
15 Histidine
318,41±18,53 448,71±15,4** 604,78±14,21** 922,5±17,06** 426,75±15,54**
16 Lysine
43,62±2,61
53,38±3,70*
74,22±2,06**
92,5±3,45**
48,8±1,96
17 Tyrosine
129,36±14,58 157,9±10,84* 214,43±8,89**
245,9±10,75** 142,07±12,41*
18 Tryptophan
66,95±3,45
78, 89±3,22*
96,68±3,93**
112,77±5,83**
71,62±4,85
105
Apparently, due to impaired melanogenesis, the formed
above amino acids are not used and accumulate in the
div.
In patients with the Setton form of the disease, the
indicators of such amino acids as methionine, glutamic
acid, isoleucine, glycine, phenylalanine, alanine, lysine,
tryptophan differed little from those of the control
group. The concentration of cysteine and histidine
differed statistically more reliably (P<0.001),
threonine, serine, leucine, valine, argenine, aspartic
acid, and tyrosine differed less reliably. The revealed
difference in the amino acid spectrum of blood in
patients with Seton's disease in comparison with other
forms of vitiligo once again confirms the data on the
versatility of etiology and pathogenesis of these clinical
forms of the disease.
When analyzing the indicators of amino acids in blood
serum depending on the activity of vitiliginous process
with the same clinical form of the disease, there was a
large discrepancy between them.
In this connection, the state of amino acid spectrum of
blood in vitiligo patients depending on the activity of
skin pathologic process is of certain interest (Table 3).
Aminoacids
Control group (п-
12) (I)
Activity of the skin pathologic process
Р (between II
and III group)
Stationary (п-11)
(II)
Progressive (п-21)
(III)
Methionine
87,98± 3,21
90,34±5,48*
99,08±6,05*
P< 0,001
Glutamic acid
76,56±4,08
92,44±6,12*
214,65±14,26**
P< 0,001
Isoleucine
63,45±4,45
71,89±3,29
126,04±6,63**
P< 0,001
Threonine
71,65±5,76
81,12±4,38*
188,25±9,31**
P< 0,001
Serine
93,14±4,8
111,32±12,36*
169,49±13,79**
P< 0,001
Glycine
59,85±2,32
66,87±3,75
162,06±8,83**
P< 0,001
Phenylalanine
53,45±2,78
48,9±2,14*
44,52±3,18*
Р< 0,05
Leucine
77,91±3,35
87,47±4,26*
151,33±7,33**
P< 0,001
Valine
103,76±6,08
122,8±6,89**
230,41±12,51**
P< 0,001
Alanine
110,4±5,58
113,31±6,38
126,55±9,82**
P< 0,001
Argenine
303,32±12,45
371,32±16,19*
792,82±21,64**
P< 0,001
Proline
222,78±13,67
255,4±13,44*
471,06±18,47**
P< 0,001
Cysteine
29,32±1,78
44,76±2,51**
213,8±14,53**
P< 0,001
Asparg. acid
79,75±3,68
96,48±4,82*
212,32±6,85**
P< 0,001
Histidine
318,41±18,53
429,92±14,33**
884,7±24,77**
P< 0,001
Lysine
43,62±2,61
64,38±3,28**
83,81±3,91**
P< 0,001
Tyrosine
129,36±14,58
148,69±9,12*
256,39±13,48**
P< 0,001
Tryptophan
66,95±3,45
87,04±3,78**
123,58±5,12**
P< 0,001
Table 3
Amino acid spectrum of blood depending on the activity of skin pathologic process
Note: * marked reliability of the difference and indicators, even P< 0.05; ** P< 0.001 when comparing with the control group.
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As can be seen from the data of Table 3, the
highest values of amino acids in blood serum of the
examined patients were found in the progressive stage
of vitiligo, especially cysteine, glutamic acid, threonine,
glycine, argenine, proline, tyrosine, aspartic acid,
histidine. The amount of phenylalanine was reduced
(P<0.05) in both groups of patients regardless of the
stage of the disease. In children with vitiligo in the
progressive stage of the disease, the indicators of 17
amino acids out of 18 studied, statistically significantly
(P<0,001) differed not only from the data of healthy
children, but also from the indicators of
vitiligo patients, the activity of the skin process which
was in the stationary stage.
The obtained data once again confirmed the
pathognomics of the revealed disaminoacidemia in
vitiligo patients, as the highest concentrations of these
amino acids and violation of their ratio were found in
the progressive stage of vitiligo regardless of the
clinical form of the disease. In patients in stationary
stage the observed hyperaminoacidemia is less reliable
than in patients in progressive stage.
Discussion
Thus, in children with vitiligo patients the
metabolism of the studied amino acids is disturbed,
ПЕДИАТРИЯ
106
more often it is manifested by increased concentration in
blood serum of cysteine - 7.4 times, histidine, glutamic
and asparagic acids - almost 3 times, isoleucine, valine,
threonine, argenine, proline, lysine - 2.1-2.5 times, the
concentration of serine, leucine, tyrosine and tryptophan
was increased in the same reliability (P<0.001). The
concentration of phenylalanine was found to be
decreased (P<0.05). Increased serum levels of cysteine,
tryptophan, tyrosine and decreased phenylalanine in
children with vitiligo are pathogenetically, in all
likelihood, associated with the underlying process, since,
as indicated above, melanogenesis and the course of
vitiligo are interrelated with the metabolism of these
amino acids. The increase of alanine, glutamic acid and
glycine in blood is probably secondary, as a consequence
of disturbance of aromatic amino acid metabolism.
The revealed changes in the ratio between
individual amino acids in vitiligo patients indicate a
pronounced disorder of amino acid metabolism,
increased ammonia formation in tissues and decreased
functional activity of hepatocytes. Increase of1.
leucine/isoleucine coefficient indicates a violation of
synthesis of plasma proteins providing homeostasis of
the organism. It should be noted that this character of
changes in children with vitiligo does not differ from2.
those in secondary metabolic disorders caused by
chronic diseases of digestive organs.
The revealed regularity, i.e. increase in blood
serum concentration of cysteine, histidine, tyrosine,
tryptophan and to a lesser extent methionine (these
amino acids participate in the process of melanogenesis
and are part of melanin) with increasing prevalence of
skin pathological process, indicates a violation of amino
acid metabolism in children with vitiligo. Apparently,
due to impaired melanogenesis, the above amino acids
formed are not utilized and accumulate in the div.
The observed highest hyperaminoacidemia in the
progressive stage of the disease is probably associated
with increased breakdown of melanocytes and melanin,
and the release of amino acids (cystine, argenine,
tyrosine, tryptophan, methionine, histidine).
Hyperaminoacidemia and violation of the ratio
between individual amino acids in the organism of
children with vitiligo, especially in its widespread forms,
indicates the importance of violation of this type of
metabolism in the pathogenesis of vitiligo and opens
new opportunities for research work in this direction.
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