RESUMEN
We describe a 17-year-old girl with haemolytic anaemia as presentation of Wilson disease. The diagnosis was based on the findings of < 20 mg/dl ceruloplasmin serum level, Kayser-Fleischer ring and Coombs-negative haemolytic anaemia. Genetic testing revealed the presence of the H1069Q heterozygous mutation. The patient was treated with Zinc acetate monotherapy, with good response, maintened after 22 months. This case emphasizes the importance of recognizing atypical clinical presentation of Wilson disease, which must always be considered in patients with Coombs-negative haemolytic anaemia. The good clinical response to treatment with zinc acetate monotherapy in our case might lend to consider the use of zinc monotherapy as initial therapy also in symptomatic patients with Wilson disease under close clinical observation. Clinical trials are needed to provide evidence for use of zinc monotherapy as first-line therapy in symptomatic patients with Wilson disease.
Asunto(s)
Degeneración Hepatolenticular/tratamiento farmacológico , Acetato de Zinc/uso terapéutico , Adolescente , Femenino , Humanos , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
We evaluated the rates of gastroenteritis admissions to the emergency department and of rotavirus-related hospitalisations in children ≤5 years of age in 2006 at an Italian paediatric hospital. We calculated the number of rotavirus cases avoidable through the universal vaccination of children. Epidemiological data were extracted from the Data Elaboration Centre. To calculate the hospitalisation rate due to rotavirus, the virus was sought in the faeces of children hospitalised for acute gastroenteritis by means of rapid immunochromatographic assay. Emergency department admissions due to gastroenteritis numbered 2,396 (11.58% of the total admissions). Of these, 276 children (11.52%) were examined and then sent home, 1,286 (53.67%) were kept in short observation and 776 (32.38%) were hospitalised. In 27.83% of hospitalised cases, the rotavirus test proved positive. The rotavirus hospitalisation rate was 55 per 10,000 children ≤5 years of age in Genoa in 2006. In 85.6% of hospitalised patients with community-acquired rotavirus infection, the disease was severe. The number of avoidable cases confirmed that the vaccination of children ≤1 year of age could reduce the burden of rotavirus infection, especially with regard to hospitalisation (45 per 10,000 children ≤5 years of age) and admissions to short observation (85 per 10,000), generating benefits for the Italian healthcare system.
Asunto(s)
Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Rotavirus/aislamiento & purificación , Vacunación/estadística & datos numéricos , Técnicas de Laboratorio Clínico/métodos , Heces/virología , Hospitalización/estadística & datos numéricos , Humanos , Italia/epidemiología , Virología/métodosRESUMEN
Rotavirus is acknowledged to be a major cause of acute gastroenteritis in infants and young children. As gastroenteritis due to rotavirus is a public health problem and two new vaccines are currently available, we investigated the rotavirus burden and developed a cost-effectiveness analysis, using data collected in the Province of Genoa (Italy), to evaluate the benefits of new borns vaccination. The cost-effectiveness of a rotavirus vaccination programme in the Province of Genoa was performed, in comparison with no vaccination, for both the regional healthcare system (RHS) and society (S). In 2006, admissions to the paediatric emergency department for gastroenteritis numbered 2338 (about 11% of total admissions); of these 33% were hospitalised. In 28% of cases, the children tested positive for rotavirus. During epidemics, paediatricians receive from 3 to 5 calls per day for gastroenteritis, carry out 1 or 2 ambulatory examinations and for children with a severe case history, make house visits. A rotavirus immunisation programme would have a great impact on disease burden, in that 90% coverage would reduce the number of severe cases by more than 85%. From the perspective of both the RHS and S, vaccination proved to be highly cost-effective.
Asunto(s)
Costo de Enfermedad , Programas de Inmunización , Infecciones por Rotavirus/economía , Adolescente , Adulto , Niño , Preescolar , Análisis Costo-Beneficio , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Modelos Económicos , VacunaciónRESUMEN
Reactivation of HBV is a well known complication in patients undergoing HSCT. Lamivudine treatment appears to prevent hepatitis B virus reactivation and to decrease the mortality in at risk HSCT patients. We describe HBV reactivation occurred in three allogeneic HSCT pediatric patients coming from Eastern Europe, one of whom was successfully treated with lamivudine. Our experience confirms that HBV-DNA may persist as intra-hepatic infection or in extra-hepatic sites and that HBV reactivation may appear during immunodepression. Careful and complete screening for HBV markers is mandatory before HSCT, especially in children coming from countries at risk for HBV. Furthermore, a treatment with lamivudine could also represent an efficacious prophylaxis in pediatric patients to avoid HBV reactivation and to decrease the development of severe hepatic disease.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hepatitis B/etiología , Hepatitis B/terapia , Hepatopatías/complicaciones , Hepatopatías/terapia , Trasplante Homólogo/efectos adversos , Adolescente , Antivirales/uso terapéutico , Niño , Antígenos de Superficie de la Hepatitis B/metabolismo , Vacunas contra Hepatitis B , Virus de la Hepatitis B/metabolismo , Humanos , Inmunosupresores/efectos adversos , Lamivudine/uso terapéutico , Masculino , Resultado del Tratamiento , Activación ViralRESUMEN
Varicella may be a severe infection in children with malignancy. Varicella vaccination is either not recommended for immunocompromised children or it requires temporary discontinuation of immunosuppression. We prospectively evaluated the feasibility of a varicella vaccination programme of household contacts of varicella-negative children receiving antineoplastic chemotherapy. From April 2004 to April 2005, 207 children were evaluated; in 49 (24 percent) the attending physicians collected no history about previous varicella and performed no serological evaluation before any transfusion. Among the 158 patients with complete history and/or a screening test, 51 (32 percent) were negative, with a total of 110 household contacts eligible for the study. Of these, 13 (12 percent) subjects resulted negative for varicella. In three of them vaccination was not performed due to parental refusal. This study demonstrates the difficulties in implementing a varicella vaccination programme targeting negative household contacts of immunocompromised children. The attitude of paediatric oncologists and parental refusal currently represent the main challenges against the complete success of this strategy in countries where VZV vaccination is not inserted in the general vaccination programme.
Asunto(s)
Antineoplásicos/efectos adversos , Cuidadores , Vacuna contra la Varicela/administración & dosificación , Varicela/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Familia , Herpes Zóster/prevención & control , Neoplasias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antineoplásicos/uso terapéutico , Cuidadores/psicología , Niño , Preescolar , Susceptibilidad a Enfermedades , Familia/psicología , Femenino , Humanos , Huésped Inmunocomprometido , Lactante , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Proyectos Piloto , Estudios Prospectivos , Negativa del Paciente al Tratamiento , Vacunación/psicologíaRESUMEN
Tuberculosis (TB) in children is an important warning sign in a community, as it could signal recent infection of a cavitary form in an adult. Thus, while early diagnosis is crucial for effective treatment in children, it is also imperative for the control of tuberculosis at the public health level since it allows rapid identification of contagious adult cases. Here we report four cases of difficult and delayed diagnosis of TB in children. From this experience we highlight the need for an extensive medical history of the patient during diagnostic work-up. This includes: the positive history for contact with infected adults, especially for immigrant children; exclusion of TB diagnosis for persistent respiratory symptoms (2-3 weeks) after antibiotic therapy; and the need for high-definition CT scan when the radiological picture is not specific, especially for children under 5 years of age.
Asunto(s)
Errores Diagnósticos , Tuberculosis/diagnóstico , Factores de Edad , Preescolar , Diagnóstico Diferencial , Transmisión de Enfermedad Infecciosa , Ecuador/etnología , Salud de la Familia , Femenino , Humanos , Lactante , Italia/epidemiología , Liberia/etnología , Masculino , Neoplasias del Mediastino/diagnóstico , Meningitis/complicaciones , Neuroblastoma/diagnóstico , Perú/etnología , Tuberculosis/epidemiología , Tuberculosis/transmisión , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Miliar/complicaciones , Tuberculosis Miliar/diagnóstico , Tuberculosis Pulmonar/diagnósticoRESUMEN
BACKGROUND AND AIMS: Little is known of hepatitis C virus (HCV) genotypes in HCV infected children. This retrospective, multicentre study investigated genotype distribution and correlation with clinical features and outcome in a large series of Italian children. METHODS: Between 1990 and 2002, 373 HCV RNA positive children, consecutively recruited in 15 centres, were assayed for genotypes by a commercial line probe assay. RESULTS: The following genotype distribution pattern was recorded: genotype 1b = 41%; 1a = 20%; 2 = 17%; 3 = 14.5%; 4 = 5%; other = 2.5%. The prevalence of genotypes 1b and 2 decreased significantly (p<0.001) among children born from 1990 onwards compared with older children (46% v 70%) while the rate of genotypes 3 and 4 increased significantly (from 8% to 30%). Children infected with genotype 3 had the highest alanine aminotransferase levels and the highest rate of spontaneous viraemia clearance within the first three years of life (32% v 3% in children with genotype 1; p<0.001). Of 96 children enrolled in interferon trials during the survey, 22% definitely lost HCV RNA, including 57% of those with genotypes 2 and 3. CONCLUSION: HCV genotypes 1 and 2 are still prevalent among infected adolescents and young adults in Italy but rates of infection with genotypes 3 and 4 are rapidly increasing among children. These changes could modify the clinical pattern of hepatitis C in forthcoming years as children infected with genotype 3 have the best chance of spontaneous viraemia clearance early in life, and respond to interferon in a high proportion of cases.
Asunto(s)
Hepacivirus/genética , Hepatitis C Crónica/genética , Adolescente , Alanina Transaminasa/metabolismo , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Genotipo , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/transmisión , Humanos , Lactante , Italia/epidemiología , Masculino , Pronóstico , ARN Viral/análisis , Estudios RetrospectivosRESUMEN
BACKGROUND AND AIM: Large interferon-based therapeutic trials are still lacking in children with hepatitis C and the long-term safety and efficacy of interferon is unknown. This study describes the outcome of hepatitis C in 43 children enrolled in an open-label interferon trial, and were followed up to 66 months after stopping treatment. PATIENTS AND METHODS: All patients received interferon alfa2a (5MU/m(2)) thrice weekly for 6 months; children with genotype 1b received 3MU/m(2) thrice weekly for 6 additional months. RESULTS: Nine children discontinued interferon for adverse events and three were not compliant to treatment. Eight (19%, intention to treat analysis), including 2/20 (10%) with genotype 1b and 6/12 (50%) with genotypes 2 or 3, were sustained responders 12 months after stopping therapy. During further follow-up (mean+/-S.D.: 44.7+/-14.6 months), response was maintained; two non-responders cleared viremia, while a young boy progressed to cirrhosis. CONCLUSIONS: Small sample size and therapy withdrawal are the major limitations in the interpretation of our results. Nevertheless, our data, suggesting that response to interferon in children with hepatitis C is genotype-related and stable, agree with the results of large studies in adults. The outcome in non-responders was variable, including persistence of viremia and mild-moderate cytolysis (most cases), progression to cirrhosis, or eventual sustained viremia clearance.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Adolescente , Antivirales/administración & dosificación , Antivirales/efectos adversos , Progresión de la Enfermedad , Femenino , Hepacivirus/genética , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , ARN Viral/análisis , Proteínas Recombinantes , Inducción de RemisiónRESUMEN
Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.
Asunto(s)
Varicela/complicaciones , Hospitalización/estadística & datos numéricos , Ataxia Cerebelosa/virología , Varicela/diagnóstico , Preescolar , Encefalitis/virología , Femenino , Hospitalización/economía , Humanos , Lactante , Clasificación Internacional de Enfermedades , Italia , Masculino , Estudios Retrospectivos , Vasculitis del Sistema Nervioso Central/virologíaRESUMEN
Twenty children with a variety of metabolic liver diseases were given two doses of hepatitis A vaccine. Adverse reactions were mild. All subjects responded to vaccine with seroconversion to hepatitis A virus antibodies after the first dose, regardless of transaminase values, and had a booster effect from the second doses.
Asunto(s)
Vacunas contra la Hepatitis A/efectos adversos , Vacunas contra la Hepatitis A/inmunología , Hepatitis A/prevención & control , Hepatopatías/inmunología , Adolescente , Niño , Preescolar , Femenino , Anticuerpos de Hepatitis A , Vacunas contra la Hepatitis A/administración & dosificación , Virus de la Hepatitis A/inmunología , Anticuerpos Antihepatitis/sangre , Humanos , Lactante , Masculino , VacunaciónRESUMEN
BACKGROUND: Compulsory vaccination of children against hepatitis B virus (HBV) infection was introduced in Italy in 1991. PATIENTS AND METHODS: To evaluate the current importance of pediatric HBV infection, we studied 359 HBsAg-positive children admitted to 16 centers in Italy from 1991 to 1998. 185 patients were natives of Italy and 174 (39 immigrants and 135 adopted) came from highly endemic countries (eastern Europe: 60.9%, Asia: 16.7%, Africa: 14.9% and Central and South America: 5.7%). RESULTS: Transaminase Levels were moderately altered in both Italian (mean 134 UI/L) and foreign children (mean 168 UI/L). In total, 77% of ItaLian children and 88% of foreign children tested HBeAg positive. High transaminase levels and HBeAg positivity were more frequent in adopted children. Follow-up of 317 patients showed that the incidence of HBeAg/anti-HBe serum conversion was similar in all cohorts, but in adopted children it occurred at an earlier age and was associated with HBsAg clearance in 5%. CONCLUSION: HBV is not frequent in Italian children today, but it is common among children coming from highly endemic areas. The vaccination of nonimmune native populations must be strongly recommended.
Asunto(s)
Vacunas contra Hepatitis B/uso terapéutico , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Adolescente , Adopción , Niño , Preescolar , Emigración e Inmigración/estadística & datos numéricos , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Programas de Inmunización , Lactante , Italia/epidemiología , MasculinoAsunto(s)
Infecciones por Virus ADN/diagnóstico , Flaviviridae , Hepatitis C/diagnóstico , Hepatitis Viral Humana/diagnóstico , Neoplasias/diagnóstico , Neoplasias/virología , Torque teno virus , Adolescente , Niño , Preescolar , Infecciones por Virus ADN/etiología , ADN Viral/sangre , Femenino , Hepatitis C/etiología , Hepatitis Viral Humana/etiología , Humanos , Masculino , Neoplasias/terapia , Estudios Prospectivos , ARN Viral/sangre , Reacción a la TransfusiónRESUMEN
In the period 1989-1999, Bacillus sphaericus was demonstrated to cause 12 out of 469 (2%) episodes of bacteraemia in children with cancer or receiving bone marrow transplant at G. Gaslini Children's Hospital, Genoa, Italy. Neutropenia was present in five episodes, six episodes, (all without neutropenia) were related to the presence of a central venous catheter, and one episode occurred in a patient with intestinal graft vs. host disease and gut colonization. All patients survived. Ciprofloxacin was the only drug active against all the isolated strains.Bacillus sphaericus represents a new cause of infection in the immunocompromised host, with low aggressiveness, but a peculiar pattern of antibiotic susceptibility.
Asunto(s)
Infecciones por Bacillaceae/etiología , Bacillus , Bacteriemia/etiología , Huésped Inmunocomprometido , Neoplasias/microbiología , Infecciones por Bacillaceae/tratamiento farmacológico , Infecciones por Bacillaceae/mortalidad , Bacillus/efectos de los fármacos , Bacteriemia/tratamiento farmacológico , Bacteriemia/mortalidad , Niño , Farmacorresistencia Microbiana , Humanos , Italia/epidemiología , Neoplasias/inmunología , Neoplasias/terapia , Factores de RiesgoRESUMEN
BACKGROUND: A retrospective-prospective survey of Italian children with hepatitis C virus (HCV) infection was planned in 1998 to explore the epidemiologic features of infection during the past decade. METHODS: Anti-HCV-positive patients (or HCV RNA-positive infants) aged 1 month to 16 years, consecutively observed in 20 pediatric Institutions, were considered. An anonymous epidemiologic questionnaire based on clinical records was used. RESULTS: From 1990 through March 1999, 606 patients were observed (296 boys, average age 5.8 years). Maternal infection (46% of cases) and blood transfusions (34%) were the most frequent risk factors. Of 279 infected mothers, 61% did not recall a putative source of infection (by history, many could possibly have had exposure through routes such as therapeutic injections with nondisposable material), whereas 94 (34%) admitted drug abuse, including 49 (17%) coinfected with human immunodeficiency virus (HIV). Only 157 (26%) children were born after 1991: 90% of their mothers were infected (11% were HIV coinfected vs. 25% mothers of older children, P < 0.01). CONCLUSIONS: Maternal infection is a prominent source of pediatric HCV infection in Italy. The fact that most mothers had a history of covert exposure to HCV, probably through percutaneous routes that are no longer operating, and that the number of those with HIV coinfection has decreased suggests that the frequency of pediatric infection could decrease in the future.
Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C/epidemiología , Adolescente , Transfusión Sanguínea , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Encuestas Epidemiológicas , Hepatitis C/etiología , Hepatitis C/transmisión , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa , Italia/epidemiología , Masculino , Prevalencia , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Abuso de Sustancias por Vía Intravenosa/complicaciones , Encuestas y CuestionariosAsunto(s)
Antivirales/uso terapéutico , Trasplante de Médula Ósea , Infecciones por Citomegalovirus/tratamiento farmacológico , Citosina/uso terapéutico , Organofosfonatos , Compuestos Organofosforados/uso terapéutico , Adenoviridae/efectos de los fármacos , Niño , Cidofovir , Citosina/análogos & derivados , Evaluación de Medicamentos , Foscarnet/efectos adversos , Ganciclovir/efectos adversos , Humanos , Huésped Inmunocomprometido , Masculino , Resultado del TratamientoRESUMEN
To value feasibility of early discharge in febrile granulocytopenic patients, 27 original paper published in the last 11 years were analyzed concerning these clinical and therapeutic approaches. A Medline search of English language literature published in the last 11 years (1988-1999) used the key words neutropenia, fever, cancer, home-antibiotic therapy, short course of antibiotic therapy, and early discharge. Twenty-seven original papers fulfilling the study criteria were identified. In these studies, 5208 episodes were evaluated: there were 538 failures with 87 deaths. Features of low-risk patients who developed life-threatening infectious disease were related to general clinical condition, cancer control, bone marrow function, presence of clinical signs of infection, and social features. Careful risk assessment can allow safe recognition of low-risk patients with febrile neutropenia who can be discharged early and can be used to follow outpatient treatment programs to improve patients' quality of life as well as the use of economic resources.
Asunto(s)
Infecciones/fisiopatología , Neoplasias/complicaciones , Neoplasias/terapia , Neutropenia/terapia , Adulto , Antibacterianos/uso terapéutico , Niño , Fiebre , Granulocitos , Humanos , Infecciones/tratamiento farmacológico , Tiempo de Internación , MEDLINE , Neoplasias/fisiopatología , Neutropenia/etiología , Alta del Paciente , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Several studies have demonstrated that hepatitis C virus (HCV) may be transmitted from mother to offspring. To date, however, little is known about the risk of vertical transmission during subsequent pregnancies. The purpose of this study was to evaluate the risk of vertical HCV transmission in offspring in subsequent pregnancies of HCV infected women. METHODS: In a multicenter study, two groups of index cases were selected. Group 1 included 75 children investigated for HCV infection during prospective studies of vertical transmission. Group 2 included children born to HCV-infected mothers and found to be HCV infected, independent of studies on vertical transmission. All children in the index cases had one or more siblings. Anti-HCV, HCV-RNA (determined by polymerase chain reaction), and HCV genotype were evaluated in all the infected children, their mothers, and siblings. RESULTS: The results indicate that a mother who has already delivered an HCV-infected baby is not at greater risk of infecting her second child. Duration of maternal infection does not seem to be a risk factor in offspring infection, because HCV infection is equally distributed among first-born infants and infants of subsequent births. Because clustering of HCV infection among siblings appeared to be rare in this study, data also indirectly confirm that the risk of horizontal transmission of HCV among siblings is low. CONCLUSION: For practical purposes, the current observations indicate that mothers who have already delivered an HCV-infected child can be advised that this event does not increase the probability of infecting the second child.
Asunto(s)
Hepatitis C/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Femenino , Genotipo , Hepacivirus/genética , Anticuerpos contra la Hepatitis C/sangre , Humanos , Lactante , Embarazo , Estudios Prospectivos , ARN Viral/análisis , Factores de RiesgoAsunto(s)
Infecciones por Virus ADN/epidemiología , Infecciones por Virus ADN/virología , Hepatitis C Crónica/complicaciones , Torque teno virus/aislamiento & purificación , Adolescente , Niño , Preescolar , Estudios Transversales , Infecciones por Virus ADN/complicaciones , Femenino , Humanos , Lactante , Italia/epidemiología , Masculino , PrevalenciaRESUMEN
X-linked lymphoproliferative disease (XLP) is a rare inherited immunodeficiency to Epstein-Barr virus (EBV). The gene responsible for XLP has recently been identified as the four-exon SH2D1A gene encoding a 128-amino-acid protein that contains an SH2-domain. Functional studies indicate the SH2D1A protein acts as a regulator of at least two signal transduction pathways initiated by the cell surface molecules SLAM and 2B4, respectively, and possibly related to the host immune response to EBV infection. We have carried out a systematic mutation study of the SH2D1A gene in our series of 19 typical and 8 atypical XLP patients by polymerase chain reaction (PCR), reverse transcription/PCR, and sequencing, and have reconstructed the haplotypes of the patients. Four out of the 13 mutations detected are previously unreported. The identification of SH2D1A mutations in carriers from all three XLP families screened and the detection of mutations in two out of eight atypical patients indicates the usefulness of a DNA-based diagnosis for XLP disease.
Asunto(s)
Proteínas Portadoras/genética , Ligamiento Genético , Péptidos y Proteínas de Señalización Intracelular , Trastornos Linfoproliferativos/genética , Mutación , Cromosoma X/genética , Análisis Mutacional de ADN , Repeticiones de Dinucleótido , Exones , Femenino , Haplotipos , Humanos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Masculino , Linaje , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genética , Proteína Asociada a la Molécula de Señalización de la Activación Linfocitaria , Dominios Homologos src/genéticaRESUMEN
In this study, we report further results of mutation analysis of the ATP7B gene in Wilson disease (WD) patients of Mediterranean origin. A total of 136 WD chromosomes, 73 of which were of Italian, 43 of Turkish, 18 of Sardinian, and two of Spanish origin, were analysed and the mutation characterised in 84.5% of them. We found 50 different mutations of which 19 are novel, including three nonsense, one frameshift, and 15 missense mutations. The mutations detected were rare and mostly found in the compound heterozygous state together with other mutations and only rarely in homozygosity. Most of these mutations lie in the transmembrane and ATP binding loop regions. These data expand our knowledge of both the structure-function relationships of the WD protein and the molecular pathology of WD, thus improving our capability of prevention and genetic counselling.