0000000000502179
AUTHOR
Lorenzo Iughetti
Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia
: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause …
Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)
Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Dat…
Combined therapy with insulin and growth hormone in 17 patients with type-1 diabetes and growth disorders.
<b><i>Background/Aim:</i></b> Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). <b><i>Methods:</i></b> A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. <b><i>Results:</i></b> Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1…
Combined therapy with insulin and rGH in thirteen Italian patients with type 1 diabetes (T1DM) and growth disorders.
Background: Combined GH and insulin therapy are rarely prescribed in pediatric pts because the association of GHD and T1DM is rare and maybe for the difficulties in managing a double therapy with opposite effects on glucose metabolism. Objective and hypotheses: To investigate on the attitude of pediatric endo-diabetologists in treating these pts. Methods: Data were collected from over 50 centres belonging to the ISPED. The inclusion criterion was based on the double therapy for at least 6 months with insulin due to T1DM, and rGH, due to growth impairment. Results: Most centres stated that the use of combined therapy was considered uncomfortable and frequently avoided, whereas 10 centres rep…
Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study
Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major…
Impaired GH secretion in patients with SHOX deficiency and efficacy of recombinant human GH therapy.
<b><i>Background/Aims:</i></b> Mutations of the short stature homeobox-containing <i>(SHOX)</i> gene on the pseudoautosomal region of the sex chromosomes cause short stature. GH treatment has been recently proposed to improve height in short patients with SHOX deficiency. The aim of this study was to evaluate GH secretion and analyze growth and safety of recombinant human GH (rhGH) therapy in short children and adolescents with SHOX deficiency. <b><i>Patients and Design:</i></b> We studied 16 patients (10 females; 9.7 ± 2.9 years old; height –2.46 ± 0.82 standard deviation score, SDS) with SHOX deficiency. All subjects underwent au…
Isolated childhood growth hormone deficiency: a 30-year experience on final height and a new prediction model
Purpose We aimed to evaluate the near-final height (nFHt) in a large cohort of pediatricpatients with growth hormone deficiency (GHD) and to elaborate a new predictive method of nFHt. Methods We recruited GHD patients diagnosed between 1987 and 2014 and followed-up until nFHt. To predict the values of nFHt, each predictor was run in a univariable spline. Results We enrolled 1051 patients. Pre-treatment height was -2.43 SDS, lower than parental height (THt) (-1.09 SDS, p < 0.001). The dose of recombinant human GH (rhGH) was 0.21mg/kg/week at start of treatment. nFHt was -1.08 SDS (height gain 1.27 SDS), higher than pre-treatment height (p < 0.001) and comparable to THt. 1.6% of the pat…
Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)
Background and aims: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). Methods: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationw…
MODELLO DI PREVISIONE DELLA STATURA FINALE IN PAZIENTI PEDIATRICI ITALIANI AFFETTI DA DEFICIT DI GH TRATTATI CON SOMATROPINA
Obiettivi: elaborare un modello di previsione della statura finale in pazienti pediatrici con deficit di GH trattati con somatropina ricombinante, valutando quali siano le variabili più importanti nel determinismo della statura finale. Metodi: 1043 pazienti trattati per deficit di GH (picco di GH <10 ng/dl a 2 test di stimolo) giunti ad altezza finale. Mediana età a inizio trattamento 11 (IQR 8.7/12.8) anni; mediana altezza a inizio trattamento -2.43 (IQR -2.80/-2.01) SDS; mediana altezza bersaglio -1.09 (IQR -1.63/-0.48) SDS; dose iniziale di somatropina mediana altezza finale -1.08 SDS (IQR -1.64/-0.50 SDS, vs altezza a inizio trattamento p <0.001, vs altezza bersaglio p=ns). Analis…