1,721,208 research outputs found
Extreme lipoprotein(a) levels in hypercholesterolemic patients: Relevance and management in pediatric population
No full textIntroduction: Elevated lipoprotein(a) levels have been considered a
causal risk factor for coronary artery disease (CAD) since many years.
Due to its biochemical structure, lipoprotein(a) may contribute to both
atherosclerosis and thrombosis. Few data are available in hypercholesterolemic
children.
Materials and methods: the aim of this study is to evaluate the prevalence
of extreme lipoprotein(a) levels in hypercholesterolemic children referring to our Lipid Center and to develop a clinical management
strategy. In a 12 months-period, 50 patients were referred to
our Lipid Center for hypercholesterolemia. 14/50 (28%) matched clinical
criteria for suspected familial hypercholesterolemia and underwent
further analysis, included dosage of lipoprotein(a). Extreme
lipoprotein(a) levels were defined as higher than 90th centile in two
different blood samples, considering adult centile as no pediatric
centile are available so far. Patients with extreme lipoprotein(a) levels
underwent a thrombophilic panel screening (thromboplastin partial
time, prothrombin time, mutation of V factor and II factor, dosage of
protein c , protein S and antithrombin III). Haematologic evaluation and
detailed CAD-oriented family history collection were also performed.
Results: 1/14 patients showed lipoprotein(a) levels higher than 90th
centile. 1/14 patient showed lipoprotein(a) level higher than 99th
centile. Among these two patients, 2/2 had positive family history for
hypercholesterolemia, 1/2 had positive family history for CAD and for
thrombosis. Thrombophilic screening showed no abnormalities. Specific
dietetic and lifestyle indications for hypercholesterolemia were
given.
Conclusions: Despite no specific pharmacological treatment is recommended
yet in pediatric patients with extreme lipoprotein(a) levels,
lipoprotein(a) levels determination is advisable in selected hypercholesterolemic
patients. Detecting pediatric patients with extreme lipoprotein(
a) levels is important in order to detect possible other
pro-thrombosis risk factors. Moreover, patients and their families are
educated to avoid the acquisition of other risk factors, such as smoking
and weight excess, and to lead a healthy lifestyle, in order to preserve
their cardiovascular health
Revised Dutch lipid clinic network score criteria adapted for pediatric age: Evaluation of this tool in pediatric patients with hypercholesterolemia
No full textIntroduction: Revised Dutch Clinic Network Score criteria (rDLCNSc)
are worldwide used to detect patients with familial hypercholesterolemia
(FH). Various Pediatric Lipid Centers have experimentally
adapted rDLCN criteria to pediatric age. The criteria included are: LDLcholesterol
levels, presence of tendon xanthoma or corneal arcus, LDLcholesterol
higher than 190 mg/dl in a parent/first degree relative (160
if aged less than 18 years), premature coronary artery disease (pCAD) in
a parent /first degree relative. “Premature” is meant before 55 years if
male and before 65 years if female. Score between 6 and 8 qualify for
probable FH, higher than 8 for definite FH.
Materials and methods: the aim of this study is to evaluate the efficacy
of rDLCNc adapted for pediatric age to select pediatric patients for DNA
mutational analysis for FH in patients referring to our Lipid Center. In a
12 months-period, 50 patients were referred to our Lipid Center for
hypercholesterolemia. rDLCNc adapted for pediatric agewas calculated
for each patient. 14/50 (28%) showed a score of 6 or higher and underwent
genetic analysis for LDL-R mutation. 2 tests are still ongoing.
Results: Among our 12 tested patients, 4/12 (33%) had a mutation of
LDL-R gene. 7/12 (58%) had positive family history for hypercholesterolemia.
0/12 had positive pCAD in parents or first degree relatives, 6/
12 (50%) had pCAD in second degree relatives. Out of the 4 patients
with positive genetic test, 3/4 (75%) had pCAD in second degree
relatives.
Conclusions: rDLCNc adapted for pediatric is a useful tool to detect
patients eligible for FH molecular diagnosis, especially in healthcare
systems with limited genetic testing resources. As children's parents
age is often lower than the threshold proposed for pCAD, they may not
have had a pCAD yet. Considering pCAD also in second degree relatives
(such as grandparents) might even improve this tool for FH detection in
pediatric populatio
THE EARLY GUT COLONIZATION IN NEW- BORNS
No full textAlthough it has been generally assumed that new-
borns are born germ free and that initial gut colonization occurs during birth, more recent studies suggest that fetal colonization begins prior to birth. Besides a possible prenatal transfer of maternal bacteria to fetus, other major determinants for neonatal gut colonization are mode of delivery, mode of feeding and perinatal antibiotic exposure. Several studies have shown effects of delivery mode on the gut micro-
biota composition of newborns. Generally, vaginally born infants are first colonized by bacteria from the maternal vagina, mainly characterized by a prevalence of Prevotella, Sneathia, and Lactobacillus genera, also including bacteria present in the maternal gut, while the gut microbiota of infants born by Cesarean (C)-section more often resembles maternal skin and oral microbiota, with a prevalence of Propionibacterium spp., Corynebacterium spp., and Streptococcus spp. Moreover, infants born by C-section have delayed colonization of Bacteroides spp., and lower microbial diversity throughout the first 2 years of life. In a previous study, we also have evaluated the relation between intestinal ecosystem of the newborn and mode of delivery by means of a molecular biology approach, collecting fecal samples on day 3 of life in 23 infants born vaginally and in 23 infants delivered by C-section. The intestinal microbiota of neonates delivered by C-section actually appeared to be less diverse, in terms of bacteria species, than the microbiota of vaginally delivered infants, being characterized by an absence of Bifidobacteria spp. Conversely, vaginally delivered neonates, although showing individual microbial profiles, were characterized by predominant groups such as B. longum and B. catenulatum. However, the effects on species diversity between different modes of delivery are reported to progressively disappear by the first year of life, when infant microbiome becomes more similar to the maternal one. It has been suggested that the early gut colonization may have long-term medical consequences: indeed, C-section delivered babies seems to display higher incidence of celiac disease, obesity and asthma, with some implications on the maturation of the immune system, in terms of lower blood levels of T-helper cell-related chemokines, possibly due to the reduced gut colonization of Bacteroides genus. Perinatal antibiotic exposure is another major determinant of early gut microbial composition in newborns. Thanks to new molecular techniques currently available, we now have proof of antibiotic-induced intestinal dysbiosis, in turn associated with intestinal and plasma lipid profile alterations. Several studies have also demonstrated that antibiotic exposure in early infancy is associated with increased risk of developing overweight/obesity, as well as asthma, wheezing and inflammatory bowel disease later in life. There has been accumulating evi-
dence that intestinal microbiota play a key role in mod-
ulating the cross-talk between brain and gut (the so called “brain-gut-enteric microbiota axis”), by means of the synthesis of many neuroactive molecules such as serotonin, melatonin, adrenaline, dopamine, ace-
tylcholine and GABA. Finally, mode of feeding also plays an important role in influencing early intestinal microbiota. Breastfeeding is undoubtedly the best way to promote the healthy development of human off-
spring as it is considered to be the optimal source for all the nutritional and functional factors that infants need. Several studies have recently proven that human milk is not sterile and it is the predominant source for establishing a “healthy microbiome” in the newborn. Milk microbial composition changes over the lactation period, being colostrum predominantly colonized by Staphylococci spp., Streptococci spp., and Lactococci spp., whereas milk samples collected later on harbor oral cavity related bacteria, perhaps due to frequent interaction with the infant’s oral microbiota. The milk microbial colonization is likely derived from mother’s gut and the elevation of progesterone levels seems to be a major cause for increasing gut permeability, thus facilitating the bacterial passage to the bloodstream and then to mammary glands. The infant’s early gut colonization is therefore modulated both by human milk microbiome and by other unique nutritional components of human milk, such as oligosaccharides and lactoferrin, also known as prebiotic or bifido-
genic factors. As a consequence, there are significant differences in the gut microbiota composition of breast-fed versus formula-fed infants. Several studies have pointed out that Bifidobacteria are the most abundant organisms in breast-fed infant guts, whereas the gut microbiota of formula-fed infants is domi-
nated by Enterococci spp. and Clostridia spp., with more species diversity. In conclusion, although the complex interaction between host and intestinal microbiota is not fully clarified yet, neonatal early gut microbial colonization seems to be a crucial step at a critical age for modulating infant’s healthy immunological, hormonal and metabolic development
Pediatric Gaucher disease type I and mild growth hormone deficiency: a new feature?
No full textA 5-year-old girl was referred to the Department
of Pediatrics and Neonatology, Guglielmo da Saliceto
Hospital, Italy, because of growth retardation. Clinical and
laboratory investigations showed pallor, hepatosplenomegaly,
anemia and low/normal platelet count. Further investigations
led to the diagnosis of Gaucher disease (GD). We
believe this is the first report of growth hormone deficiency
in a growth-retarded child with GD. After 1 year of
imiglucerase replacement enzyme therapy, her bone age
had normalized, linear growth rate had accelerated, and
insulin growth factor-1 (IGF-1) and, perhaps more interestingly,
growth hormone deficiency, had normalized. While
the pathophysiological mechanisms underlying compromised
growth in GD are poorly understood, the response
to imiglucerase reported in this patient suggests that growth
hormone deficiency is related to the underlying metabolic
disorder in GD, rather than a primary endocrine pathology.
Growth hormone deficiency adds to an already extensive
list of possible clinical manifestations of this heterogeneous
and complex disorder
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