Cerebral and systemic near infrared spectroscopy patterns in preterm infants treated by caffeine.

AIM: To investigate the effects of caffeine loading/maintenance administration on near-infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. METHODS: We conducted a multicentre case-control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. RESULTS: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. CONCLUSION: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long-term effect of caffeine in preterm infants.

Benefits of a prolonged-release amino acid mixture in four pregnant women with phenylketonuria.

Background: Maternal phenylketonuria (mPKU) is a pathologic condition occurring in the fetus of a mother with PKU that is caused by prolonged elevated intrauterine blood phenylalanine (Phe) levels, which can lead to congenital abnormalities and mental retardation of newborns. Management of PKU during pregnancy can be challenging as protein substitutes may exacerbate nausea, vomiting, and gastrointestinal symptoms. Aim: To report the successful management of four PKU pregnant women. Methods: The patients were administered with prolonged-release amino acid supplementation and were recommended to follow a strict diet. Blood Phe concentration, adherence to diet, and occurrence of adverse events were monitored. Results: All patients achieved safe levels of blood Phe concentration (120-360 µmol/L) since preconception and during pregnancy (mean Phe concentration values of 143.34 ± 137.59, 226.48 ± 194.57, 186.68 ± 133.67, and 187.47 ± 42.59 µmol/L). During the first trimester of pregnancy, all patients manifested gastrointestinal symptoms such as nausea, gastrointestinal reflux, and abdominal bloating, which were managed by either changing protein substitute or extending the time window between different meals and amino acid mixtures administration. The four women continued their pregnancies without experiencing further complications and delivered neonates with normal growth parameters and no malformations. Conclusion: Findings of this case series suggest that the intake of a prolonged-release amino acid mixture in granules is well tolerated by pregnant PKU patients, eventually leading to good metabolic control and fetal growth within normal ranges.

c.376A>G, (p.Ser126Gly) Alpha-Galactosidase A mutation induces ER stress, unfolded protein response and reduced enzyme trafficking to lysosome: Possible relevance in the pathogenesis of late-onset forms of Fabry Disease.

Fabry Disease (FD) (OMIM 301500) is a metabolic X-linked inherited lysosomal storage disorder that results from the deficient activity of Alpha-Galactosidase A (Alpha-Gal), a lysosomal hydrolase that cleaves neutral glycosphingolipids with terminal N-linked galactosyl moieties, mainly globotriaosylceramides (Gb3). The enzyme, encoded by a 12-kb gene mapping on the long arm (Xq22.1 region) of the X chromosome, is constituted by a glycosylated subunit of approximately 55 kD, synthesized as an inactive precursor that undergoes maturation in endoplasmic reticulum (ER) and Golgi apparatus before being delivered to the lysosome to form a functional dimer. The gene is comprised of seven exons and, so far, >1000 different mutations have been described as associated to FD (www.dbfgp.org/dbFgp/fabry/FabryGP.htm). Clinical phenotypes are divided in two main classes, classic or non-classic, based on clinical and biochemical findings. Non-classic FD, usually recognized as late-onset forms with oligosymptomatic phenotype, presents with symptoms restricted solely to cardiocytes, kidneys or brain associated to missense misfolding mutations. In the group of the non-classic FD, special attention should be given to patients carrying the c.376A > G (p.Ser126Gly) mutation. The lack of clear experimental evidences on its pathogenetic role, despite the clinical pictures of the patients with severe ischaemic lesions, renal involvement and acroparesthesias, led many authors to classify this mutation as inconsistent, non-pathogenetic, and consequently not eligible to the current pharmacological treatments for FD. To shed light on the cellular processes affected by this mutation and to assess if the biochemical pathways involved with, could really have a significant pathogenetic impact, we studied the mutation in silico and in COS-7 and HEK 293 cell models. We found p.Ser126Gly, even retaining both high degree of synthesis and residual activity, is mostly stacked into the ER inducing unfolded protein response (UPR) with reduced trafficking to the lysosome. These data strongly suggest that p.Ser126Gly could trigger a pathogenetic mechanism different from the classic and well assessed increased turnover with loss of biological activity described for other missense mutations. This mechanism seems mainly related to a negative gain of function, with ER retention and UPR activation and could lead, via inflammation and/or apoptosis, to irreversible cell damage.

Epilepsy, electroclinical features, and long-term outcomes in Pitt-Hopkins syndrome due to pathogenic variants in the TCF4 gene.

BACKGROUND AND PURPOSE: Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by deletions/variants in the TCF4 gene. Seizures may be present in up to half of the patients, leading to a more severe disease burden. This study aims to analyse the electroclinical phenotype, treatment options, and long-term outcomes of epilepsy in PTHS. METHODS: A multicentre observational cohort study was performed, and the electroclinical data of PTHS individuals affected by epileptic seizures were retrospectively reviewed and analysed. RESULTS: The series includes 21 patients (11 female) with a median age at seizure onset of 2 years (range = 0.5-8). The median time of follow-up was 7.9 years (range = 2-27). Both generalized and focal epilepsies were present at the same prevalence (42.8%), whereas a minority of patients presented developmental and epileptic encephalopathies (14.4%). At the long-term follow-up, 42.8% achieved seizure freedom, whereas 42.8% developed drug-resistant epilepsy (DRE). The age at seizure onset was found to be an independent predictor for seizure outcome; in this regard, patients having seizure onset after the age of 2 years were more prone to achieve seizure freedom (odds ratio = 0.04, 95% confidence interval = 0.003-0.53; p = 0.01). During evolution, seizures tended to settle down, and even in patients with DRE, seizures tended to persist at a lower frequency and appeared to be more easily manageable over time. CONCLUSIONS: This study provides new insight into the natural history of epilepsy in PTHS. Better characterization of epileptic phenotype and prompt tailored treatment improve overall management and quality of life.

Fabry disease and kidney involvement: starting from childhood to understand the future.

The accumulation of globotriaosylceramide (Gb-3) in multiple organs, such as the heart, kidney, and nervous system, due to mutations in the galactosidase alpha (GLA) gene, represents the key point of Fabry disease (FD). The common symptoms appear in childhood or adolescence, including neuropathic pain, angiokeratoma, acroparesthesia, and corneal opacities. A multi-organ involvement induces a significant deterioration in the quality of life with high mortality in adulthood. The accumulation of Gb-3 involves all types of kidney cells beginning at fetal development, many years before clinical manifestations. A decline in the glomerular filtration rate is rare in children, but it can occur during adolescence. Pediatric patients rarely undergo kidney biopsy that could assess the efficacy of enzyme replacement therapy (ERT) behind its diagnostic role. To date, diagnosis is achieved by detecting reduced α-Gal-A activity in leukocytes and plasma, allowing for the early start of ERT. This review focuses on pediatric kidney involvement in FD, analyzing in depth its diagnostic processes and treatment options.

Gelastic seizures not associated with hypothalamic hamartoma: A long-term follow-up study.

OBJECTIVE: The objective of the study was to describe the electroclinical features, seizure semiology, and the long-term evolution of gelastic seizures (GS) not associated with hypothalamic hamartoma (HH). METHODS: We reviewed video-electroencephalogram (video-EEG) recordings from pediatric patients with GS without HH admitted to 14 Italian epilepsy centers from 1994 to 2013. We collected information about age at onset, seizures semiology, EEG and magnetic resonance imaging (MRI) findings, treatment, and clinical outcome in terms of seizure control after a long-term follow-up. RESULTS: A total of 30 pediatric patients were stratified into two groups according to neuroimaging findings: group 1 including 19 children (63.3%) with unremarkable neuroimaging and group 2 including 11 children with structural brain abnormalities (36.7%). At the follow-up, patients of group 1 showed better clinical outcome both in terms of seizure control and use of AED polytherapy. Our patients showed remarkable clinical heterogeneity, including seizure semiology and epilepsy severity. Electroencephalogram recordings showed abnormalities mainly in the frontal, temporal, and frontotemporal regions without relevant differences between the two groups. Overall, carbamazepine showed good efficacy to control GS. CONCLUSIONS: Patients with nonlesional GS have a more favorable outcome with better drug response, less need of polytherapy, and good long-term prognosis, both in terms of seizure control and EEG findings.

A 46,XY Female with a 9p24.3p24.1 Deletion and a 8q24.11q24.3 Duplication: A Case Report and Review of the Literature.

Deletion of distal 9p is associated with a rare clinical condition characterized by dysmorphic features, developmental delay, and ambiguous genitalia. The phenotype shows variable expressivity and is related to the size of the deletion. 8q24 duplication has been reported in only few cases to date, all showing dysmorphic features and mild psychomotor developmental delay. A case of chromosomal aberration involving a 9p terminal deletion with an 8q duplication has never been reported. Here, we describe a child with a female phenotype, male karyotype, dysmorphic features, ambiguous genitalia, and developmental delay. In order to assess the cause of the patient's phenotype, conventional karyotyping, FISH, and a chromosomal microarray analysis were performed on the patient and her parents. The cytogenetic and molecular analysis revealed an unbalanced chromosomal aberration with a duplication in the long arm of chromosome 8 at 8q24.11q24.3 associated with a distal deletion in the short arm of chromosome 9 at 9p24.3p24.1, derived from a maternal balanced translocation. We compared the clinical picture of our patient with other similar cases reported in the literature and found that some clinical findings, such as strabismus, symphalangism of the first finger, and cubitus valgus, have never been previously associated with 9p deletion or 8q duplication expanding the phenotypic range of this condition. This study is aimed to better define the clinical history and prognosis of patients with this rare chromosomal aberration.

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study.

Mucopolysaccharidoses (MPS) are a subgroup of 11 monogenic lysosomal storage disorders due to the deficit of activity of the lysosomal hydrolases deputed to the degradation of mucopolysaccharides. Although individually rare, all together they account for at least 1:25,000 live births. In this study, we present the genetic analysis of a population of 71 MPS patients enrolled in a multicenter Italian study. We re-annotated all variants, according to the latest recommendations, and re-classified them as suggested by the American College of Medical Genetics and Genomics. Variant distribution per type was mainly represented by missense mutations. Overall, 10 patients had received no molecular diagnosis, although 6 of them had undergone either HSCT or ERT, based on clinical and enzymatic evaluations. Moreover, nine novel variants are reported.Conclusions: Our analysis underlines the need to complete the molecular diagnosis in patients previously diagnosed only on a biochemical basis, suggests a periodical re-annotation of the variants and solicits their deposition in public databases freely available to clinicians and researchers. We strongly recommend a molecular diagnosis based on the analysis of the "trio" instead of the sole proband. These recommendations will help to obtain a complete and correct diagnosis of mucopolysaccharidosis, rendering also possible genetic counseling. What is known • MPS are a group of 11 metabolic genetic disorders due to deficits of enzymes involved in the mucopolysaccharides degradation. • Molecular analysis is commonly performed to confirm enzymatic assays. What is new • Eighty-six percent of the 71 patients we collected received a molecular diagnosis; among them, 9 novel variants were reported. • We stress the importance of molecular diagnosis in biochemically diagnosed patients, encourage a periodical re-annotation of variants according to the recent nomenclature and their publication in open databases.

Composition and structure of glycosaminoglycans in DBS from 2-3-day-old newborns for the diagnosis of mucopolysaccharidosis.

Dried blood spot (DBS) technology is a cheap and easy method largely applied in newborn screening. Mucopolysaccharidoses (MPS) are characterized by the deficit of enzymes that degrade glycosaminoglycans (GAGs) characterized by progressive worsening of the conditions. For a possible early diagnosis of MPS, we developed a method of uronic acid (UA)-GAGs determination in DBS of 600 healthy newborns and from a small group of MPS subjects matched for age. Spotted blood UA-GAGs of the normal newborns are composed of 67.2% chondroitin sulfate (CS), 28.6% heparan sulfate (HS) and 4.4% hyaluronic acid with a CS/HS ratio of 2.35 and a total GAGs content of 0.43 µg/DBS. A chemical evaluation of CS and HS structure was performed by measuring their disaccharide composition, sulfation and the overall charge density. The DBS of four different MPS types presented an increase of total or single UA-GAGs content and/or modifications of the CS and HS disaccharide composition as well as chemical signature also related to the MPS enzymatic defect. The modifications of the UA-GAGs composition, parameters and structure of healthy newborns determined in DBS would be useful for a possible early diagnosis of various MPS types.

Parapelvic cysts, a distinguishing feature of renal Fabry disease.

Background: Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear. Methods: The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1). Results: In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P < 0.001). The presence of other renal abnormalities did not differ between the groups, nor differences exist in the main demographic and laboratory parameters between the groups. In Study 2, the greater accuracy of ultrasound increased PC prevalence from 29.8% to 43.3% in the same subjects (P < 0.05). In both studies, no correlation was detected between PC and the main demographic, clinical and biochemical parameters, including use of enzyme replacement therapy (P < 0.1, minimum value). Finally, no difference existed between FD patients with and without PC. Conclusions: The present study suggests that the presence of PC in renal patients should alert physicians to consider the diagnosis of FD, primarily in subjects with an unclear family history of renal disease and in the presence of other stigmata of the disease.

Norrbottnian clinical variant of Gaucher disease in Southern Italy.

The Norrbottnian type of Gaucher disease (GD), as described many years ago, is due to a unique neuronopathic variant (c.1448T>G; L444P) that may have appeared during or before the sixteenth century in northern Sweden. It is a well-defined nosological entity with a characteristic course of clinical manifestations. In particular, Norrbottnian patients described in Sweden and Poland seem to share identical clinical histories characterized by the early onset of significant hepatosplenomegaly, often requiring splenectomy at an early age. Neurological involvement generally appears during the first or second decade of life, and includes horizontal gaze palsy, epilepsy, myoclonic movements, ataxia, dementia and cognitive impairment. Osteopenia occurs primarily in the spine, causing a severe and progressive thoracic kyphosis, although the involvement of other skeletal sites cannot be excluded. Here, we report on four Gaucher type 3 patients with Southern Italian ancestry presenting with clinical features and disease progression comparable to those of the 'Norrbottnian' Swedish phenotype, particularly regarding skeletal involvement with poor responsiveness to any therapeutical approach. Although a common ancestry among Southern Italian and Swedish Norrbottnian GD patients could not be investigated, the genotype [L444P]+[L444P] is the most frequently encountered in Southern Italy.

Corpus callosum involvement: a useful clue for differentiating Fabry Disease from Multiple Sclerosis.

PURPOSE: Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. METHODS: In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. RESULTS: WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. CONCLUSION: FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options.

Clinical heterogeneity of dominant chronic mucocutaneous candidiasis disease: presenting as treatment-resistant candidiasis and chronic lung disease.

In gain-of-function STAT1 mutations, chronic mucocutaneous candidiasis disease (CMCD) represents the phenotypic manifestation of a complex immunodeficiency characterized by clinical and immunological heterogeneity. We aimed to study clinical manifestations, long-term complications, molecular basis, and immune profile of patients with dominant CMCD. We identified nine patients with heterozygous mutations in STAT1, including novel amino acid substitutions (L283M, L351F, L400V). High risk of azole-resistance was observed, particularly when intermittent regimens of antifungal treatment or use of suboptimal dosage occurs. We report a case of Cryptococcosis and various bacterial and viral infections. Risk of developing bronchiectasis in early childhood or gradually evolving to chronic lung disease in adolescent or adult ages emerges. Lymphopenia is variable, likely progressing by adulthood. We conclude that continuous antifungal prophylaxis associated to drug monitoring might prevent resistance to treatment; prompt diagnosis and therapy of lung disease might control long-term progression; careful monitoring of lymphopenia-related infections might improve prognosis.

Optimizing the molecular diagnosis of GALNS: novel methods to define and characterize Morquio-A syndrome-associated mutations.

Morquio A syndrome (MPS IVA) is a systemic lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), encoded by the GALNS gene. We studied 37 MPS IV A patients and defined genotype-phenotype correlations based on clinical data, biochemical assays, molecular analyses, and in silico structural analyses of associated mutations. We found that standard sequencing procedures, albeit identifying 14 novel small GALNS genetic lesions, failed to characterize the second disease-causing mutation in the 16% of the patients' cohort. To address this drawback and uncover potential gross GALNS rearrangements, we developed molecular procedures (CNV [copy-number variation] assays, QF-PCRs [quantitative fluorescent-PCRs]), endorsed by CGH-arrays. Using this approach, we characterized two new large deletions and their corresponding breakpoints. Both deletions were heterozygous and included the first exon of the PIEZO1 gene, which is associated with dehydrated hereditary stomatocitosis, an autosomal-dominant syndrome. In addition, we characterized the new GALNS intronic lesion c.245-11C>G causing m-RNA defects, although identified outside the GT/AG splice pair. We estimated the occurrence of the disease in the Italian population to be approximately 1:300,000 live births and defined a molecular testing algorithm designed to help diagnosing MPS IVA and foreseeing disease progression.

Postinfectious functional gastrointestinal disorders in children: a multicenter prospective study.

OBJECTIVES: To prospectively investigate the occurrence of postinfectious functional gastrointestinal disorders (FGIDs), diagnosed according to the Rome III criteria, in children with acute diarrhea of different infectious etiology. STUDY DESIGN: This was a prospective cohort multicenter study. Children 4-17 years of age presenting with acute diarrhea who tested positive for an enteric infection were recruited within 1 month from the episode and matched with control subjects of similar age and sex. Symptoms were evaluated with a validated questionnaire for FGIDs at the time of enrollment in the study and after 3 and 6 months. RESULTS: A total of 64 patients (36 boys; median age 5.3 years; age range 4.1-14.1 years) were recruited, 32 subjects in each arm. Infections included rotavirus (56.8%), salmonella (30%), adenovirus (6.6%), norovirus (3.3%), and Giardia lamblia (3.3%). FGIDs were significantly more common in exposed patients compared with controls within 1 month from acute diarrhea (40.6% vs 12.5% [P = .02, relative risk (RR) = 1.9]), 3 months (53% vs 15.6% [P = .003, RR = 2.2]), and 6 months (46.8% vs 15.6% [P = .01, RR = 1.9]) later. No correlation was found between different etiologies, age, or sex, and any type of FGIDs. Among exposed children, abdominal pain-related FGIDs were significantly more frequent compared with controls after 6 months from infection (P = .04, RR = 1.7). CONCLUSION: This prospective cohort multicenter study supports postinfectious FGIDs as a true entity in children. There seems to be a significant increase in abdominal pain-related FGIDs after acute diarrhea in children within 1 month and 3 and 6 months later.

Long term effects of enzyme replacement therapy in an Italian cohort of type 3 Gaucher patients.

BACKGROUND: The chronic neuropathic form of Gaucher disease (GD3) is characterised by hepatosplenomegaly, anaemia, thrombocytopenia, bone alterations and central neurological involvement. Enzyme replacement therapy (ERT) has been demonstrated to be effective in non neuropathic Gaucher disease, but long term results in patients with GD3 are still limited and contrasting. A possible role of genotype in determining the response to ERT has been hypothesised. PATIENTS AND METHODS: All patients affected by GD3, treated with ERT, and followed-up in 4 different Italian centres (Udine, Catanzaro, Sassari and Florence) were included. Data on clinical conditions, laboratory values, neurological and neuropsychological examinations, radiological and electrophysiological features were collected retrospectively from clinical records. RESULTS: Ten patients (6 females, 4 males) with four different genotypes (L444P/L444P, L444P/F231I, P159T/unknown, C.115+1G>A/N188S) were identified. They received ERT infusions from 3 to 21years. Haematological parameters and organomegaly improved/normalised in all patients. Three patients showed severe progressive skeletal deformities. 6/10 patients were neurologically asymptomatic when they started ERT for systemic symptoms. During the follow-up, 2/6 developed an important central nervous system disease; 2/6 developed mild central symptoms; and 2/6 did not show any neurological symptom after 5, and 20years of treatment respectively, despite the presence of epileptiform abnormalities at the electroencephalogram. Overall, neurological involvement worsened over time in 6/10 patients, 3 of whom developed progressive myoclonic encephalopathy and died. CONCLUSIONS: ERT improved the systemic manifestations in patients with GD3, but was not able to counteract the progression of neurological symptoms in the long term.

Myoglobinuria as first clinical sign of a primary alpha-sarcoglycanopathy.

UNLABELLED: Myoglobinuria is a frequent complication of metabolic myopathies and may also occur in Duchenne and Becker dystrophies but is not a typical sign of limb-girdle muscular dystrophy. We describe an unusual presentation of alpha-sarcoglycanopathy with myoglobinuria at the onset of the disease. The boy presented an episode of dark urine, identified as presence of blood by a urine dipstick, occurred 10 days after an episode of fever and sore throat treated with antibiotics. He was admitted to the hospital and investigated for post-infectious nephritis, but further analysis revealed the presence of myoglobinuria. Immunohistochemistry on muscle tissue revealed absent expression of α-sarcoglycan confirmed by detection of a homozygous mutation in the alpha-sarcoglycan gene. Myoglobinuria has been previously reported four times in sarcoglycanopathies but only once in alpha-sarcoglycanopathy. CONCLUSION: The present observation reinforces the idea that the myoglobinuria should be considered a manifestation of a primary sarcoglycanopathy even as the only recognizable sign at the debut of the disease.

Successful management of neonatal renal venous thrombosis.

Renal vein thrombosis is the most common vascular condition involving the newborn kidney and it can result in severe renal damage. We report a newborn with renal vein thrombosis treated with continuous infusion of unfractionated heparin who had normal total renal function after 3 years of follow up, despite reduction of the functional contribution of the affected kidney.

Point of care lung ultrasound in preschool children with cystic fibrosis: a case-controlled, prospective, pilot study.

AIMS: Respiratory complications in Cystic Fibrosis (CF) are still the leading cause of death nowadays in these patients. High-Resolution Computed Tomography is the gold standard method for staging lung disease in CF. In this study we assessed lung ultrasound findings in asymptomatic preschool patients affected by CF. METHODS: This is a case-control study with a total of 70 enrolled patients (20 patients affected by CF, 50 healthy controls) aged from 31 to 6 years. All included patients were without intercurrent lung problems and without antibiotic therapy in the last 30 days. For each patient a lung Point of Care Ultrasound (POCUS) of lung was performed. RESULTS: B lines < 3 and sub-pleural consolidations < 1 cm were statistically more frequent in CF patients, both in terms of number of affected patients (p 0.02 and p 0.0001 respectively) and frequency (p 0.0181 and p 0.0001 respectively); the prevalence of B lines < 3 in control group was high (47.73%) however the prevalence of sub-pleural consolidations was very low (2.27%). In both groups coalescent B lines affected a greater number of infants and were in higher number of findings than patients aged between 2 and 6 years. CONCLUSIONS: The presence of multiple subpleural pulmonary consolidations < 1 cm in asymptomatic preschool children could be a ultrasound markers of subclinical pulmonary disease such as CF. POCUS of lung is confirmed as a useful tool for the clinician as confirmation of a clinical suspicion, help reduce the use of ionizing radiation.