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J Urol Ren Dis, an open access journal
ISSN: 2575-7903
1Volume 4; Issue 01
Journal of Urology and Renal Diseases
Mini-Review
Fontes LBC, et al. J Urol Ren Dis 4: 1136.
Urinary Recurrent Infection in Children with Autism Spectrum Disorder
Luciana de Barros Correia Fontes*, Maria da Conceição de Barros Correia, Cláudia Wanderley de Barros Correia, Valter
Romão de Souza Júnior, Virgínia Paula Batista de Brito
Federal University of Pernambuco, Moraes Rego,Brazil
*Corresponding author: Luciana de Barros Correia Fontes, Rua Ester Foigel, 110, ap. 1102, Iputinga, 50721440. Recife, Pernam-
buco, Brazil. Email: lu.bc.f@hotmail.com
Citation: Fontes LBC, Correia MCB, Correia CWB, Júnior VRS, Brito VPB (2019) Urinary Recurrent Infection in Children with
Autism Spectrum Disorder. J Urol Ren Dis 4: 1136. DOI: 10.29011/2575-7903.001136
Received Date: 28 January, 2018; Accepted Date: 18 February, 2019; Published Date: 22 February, 2019
DOI: 10.29011/2575-7903.001136
With the increase estimate in the prevalence of Autism
Spectrum Disorders (ASD) in the world, much research has been
directed to this emerging public health problem. However, despite
evidence in the literature, yet there is little discussion about the
possibility and treatment of recurrent urinary tract infections in
children with this specicity.
Autism Spectrum Disorder (ASD) is a
neuropsychiatric disorder with onset during early childhood
and life-long consequences in most cases. It is characterized by
impairment in social interaction and communication, as well as
by restricted patterns of interest and stereotyped behaviors. The
etiology of autism is highly heterogeneous, encompassing a
large range of genetic and environmental factors. Several lines of
evidence suggest that, in addition to broader diagnostic criteria and
increased awareness, also a real increase in incidence primarily due
to greater gene-environment interactions may also be occurring
[1,2].
There is a higher prevalence of prenatal, perinatal and
postnatal factors in children with ASD in comparison with
unaffected sibilings, particularly male gender, acute fetal distress,
difcult labor, respiratory infection and prenatal urinary tract
infection. Perinatal complications of pregnancies and medical
conditions of the mother were found to be highly signicant,
including depression, high temperatures and urinary infection [3].
Among specic diagnoses, upper respiratory infections
were signicantly less frequently diagnosed and genitourinary
infections more frequently diagnosed in children with autism. In
the rst 30 days of life, the frequency of having an infection was
slightly higher among children with autism [4].
Autism disorder has associated metabolic
abnormalities. Autistic children showing higher levels
of urinary taurine and a lower level of urinary glutamate,
indicating perturbation in sulfur and amino acid metabolism in
these children. Additionally, metabolic phenotype (metabotype)
differences were observed between autistic and others children,
which were associated with perturbations in the relative patterns
of urinary mammalian-microbial cometabolites including
dimethylamine, hippurate, and phenyacetylglutamine. These
biochemical changes are consistent with some of the known
abnormalities of gut microbiota found in autistic individuals and
the associated gastrointestinal dysfunction and may be of value in
monitoring the success of therapeutic interventions [5].
Clinical chemistry tests for ASD are currently unavailable,
but proteotoxic biomarkers in plasma and urine have been
investigated for the clinical diagnosis of autism. Children with
ASD had increased Advanced Glycation Endproducts (AGEs), Nε-
Carboxymethyl-Lysine (CML) and N
ω-Carboxymethylarginine
(CMA), and increased oxidation damage marker, Dityrosine (DT),
in plasma protein, with respect to healthy controls. And they also
had increased CMA free adduct in plasma ultraltrate and increased
urinary excretion of oxidation free adducts, alpha-aminoadipic
semialdehyde and glutamic semialdehyde. From study of renal
handling of amino acids, children with ASD had decreased renal
clearance of arginine and CMA with respect to healthy controls
[6,7].
Many individuals on the autism spectrum have signicantly
higher CAT activity and concomitant lower TAC and TTM
concentration in comparison withouth this characteristics and
specicities. There is an increased vulnerability to oxidative
damage, which may contribute to the development and clinical
manifestation of symptoms of autism [6]. Studies have been
explored the diagnostic utility of proteotoxic biomarkers in
plasma and urine, plasma protein gycation, oxidation, and nitration
adducts, and related glycated , oxidized, and nitrated amino acids
(free adducts), for the clinical diagnosis of ASD [8].
It was described in autistic patients an overgrowth of unusual
gut bacterial strains, able to push the fermentation of tyrosine up
to the formation of p-cresol. Urinary p-cresol was signicantly
elevated in autistic children smaller than 8 years of age, typically
Citation: Fontes LBC, Correia MCB, Correia CWB, Júnior VRS, Brito VPB (2019) Urinary Recurrent Infection in Children with Autism Spectrum Disorder. J Urol Ren
Dis 4: 1136. DOI: 10.29011/2575-7903.001136
2Volume 4; Issue 01
J Urol Ren Dis, an open access journal
ISSN: 2575-7903
females, and more severely affected regardless of sex. Urinary
cotinine measurements excluded smoking-related hydrocarbon
contaminations as contributors to these differences. Hence, elevated
urinary p-cresol may serve as a biomarker of autismliability in
small children, especially females and more severely affected
males [9]. Environmental exposure to the organic aromatic
compound p-cresol (4-methylphenol) is relatively common
and occurs through the skin, as well as the gastrointestinal and
respiratory systems. However, the largest and most widespread
source of this compound is represented by some gut bacteria
which express p-cresol synthesizing enzymes not found in human
cells. Urinary p-cresol and its conjugated derivative p-cresylsulfate
have been found elevated in an initial sample and recently in a
replica sample of autistic children below 8 years of age, where it is
associated with female sex, greater clinical severity regardless of
sex, and history of behavioral regression [10].
Elevated p-cresol amounts have been
previously found in the urines of Italian and
French autism spectrum disorder(ASD) children up until 8 years
of age, and may be associated with autism severity or with the
intensity of abnormal behaviors. urinary p-cresol levels are
elevated in young ASD children with increased intestinal transit
time and chronic constipation . Bladder and Bowel Dysfunction
(BBD) describes a spectrum of Lower Urinary Symptoms (LUTS)
accompanied by fecal elimination issues that manifest primarily
by constipation and/or encopresis. This increasingly common
entity is a potential cause of signicant physical and psychosocial
burden for children and families. BBD is commonly associated
with Vesicoureteral Reux (VUR) and recurrent Urinary Tract
Infections (UTIs), which at its extreme may lead to renal scarring
and kidney failure. Additionally, BBD is frequently seen in children
diagnosed with behavioural and neuropsychiatric disorders such
as Attention-Decit/Hyperactivity Disorder (ADHD) and ASD.
Patients with concomitant BBD and neuropsychiatric disorders
have less favourable treatment outcomes. Early diagnosis and
treatment of BBD are critical to avoid secondary comorbidities
that can adversely impact children’s kidney and bladder function,
and psychosocial well-being [9,10].
A compound identied as 3-(3-hydroxyphenyl)-
3-hydroxypropionic acid (HPHPA) was found in higher
concentrations in urine samples of children with autism compared
to age and sex appropriate controls and in an adult with recurrent
diarrhea due to Clostridium difcile infections. The highest value
measured in urine samples was 7500 mmol/mol creatinine, a value
300 times the median normal adult value, in a patient with acute
schizophrenia during an acute psychotic episode. The signicance
of this compound is that it is a probable metabolite of m-tyrosine
(3-hydroxyphenylalanine), a tyrosine analog which depletes brain
catecholamines and causes symptoms of autism (stereotypical
behavior, hyperactivity, and hyper-reactivity) in experimental
animals [11]. Urinary levels of p-cresol and p-cresylsulfate were
associated with stereotypic, compulsive/repetitive behaviors,
although not with overall autism severity. The elevation of
urinary p-cresol in a sizable set of small autistic children and
spur interest into biomarker roles for p-cresol and p-cresylsulfate
in autism.
It is necessary to deepen the possible recurrent urinary
infections in autistic children, especially before neurological
maturation, in order to contribute effectively to the development
and quality of life of this target group.
References
Persico AM, Napolioni V (2013) Urinary p-cresol in autism spectrum 1.
disorder. Neurotoxicol Teratol 36: 82-90.
Gabriele S, Sacco R, Altieri L, Neri C, Urbani A, et al. (2016) Slow 2.
intestinal transit contributes to elevate urinary p-cresol level in italian
autistic children. Autism Res 9: 752-759.
Hadjakacem I, Ayadi H, Turki M, Yaichi S, Khemekhem K, et al. (2016) 3.
Prenatal, perinatal and postnatal factors associated with autism spec-
trum disorder. Pediatr 92: 595-596.
Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, et al. (2010) 4.
Urinary metabolic plhnotyping differentiates children with autismo from
their unaffected siblings and age-mached controls. J Proteome Res 9:
2996-3004.
Omura Y, Lu D, Jones MK, Nihrane A, Duvvi H, et al. (2015) Early 5.
detection of autismo (ASD) by a non-invasive quick measurement
of markedly reduced acetylcholine & DEA and increased ß-Amyloid
(1-42), Asbestos (Chrysotile), Titanium Dioxide, Al, Hg & often coexist-
ing vírus infections (CMV, HPV 16 and 18). Bacterial intentions etc. in
the brain and corresponding safe individualized effective treatment.
Acupnc Electrother Res 40: 157-87.
Attia A, Provvidenza MA, Sabah P, Kashif R, Alessandra B, et al. (2018) 6.
Advanced glycation endproducts, dityrosine and arginine transporter
dysfunction in autismo - a source of biomarkers for clinical diagnosis.
Molecular Autism 9 :3.
Ranjbar A, Rashedi V, Rezaei M (2014) Comparison of urinary oxida-7.
tive biomarkers in Iranian children with autism. Rev Dev Disabil 35:
2751-2755.
Altieri L, Nery C, Sacco R, Curatolo P, Benvenuto A, et al. (2011) Uri-8.
nary p-cresol is elevated in small children with severe autism spectrum
disorders. Biomarkers 16: 252-260.
Santos JD, Lopes,RI, Koyle MA (2017) Bladder and bowel dysfunction 9.
in children: an update on the diagnosis and treatment of a common, but
underdiagnosed pediatric problem. Can Urol Assoc J 11: S64-S72.
Shaw W (2010) Increased urinary excretion of a 3-(3-hydroxyphenyl)-10.
3-hydroxyproprionic acid (HPHPA), na abnormal phenylanine metabo-
lite of Clostridia spp. In the gastrointestinal tract, in urine samples from
patients with autismo and schizophrenia. Nutr Neurosci 13: 135-143.
Gabriele R, Sacco R, Cerullo S, Neri C, Urbani A, et al. (2014) Urinary 11.
p-cresol is elevated in young French children with autism spectrum
disorder: a replication study. Biomarkers 19: 463-470.
