Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy

Background: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. Objectives: To provide epidemiological data of EPP in Italy. Materials and Methods: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017). Results: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed 6410 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67\u2009+\u20095G\u2009>\u2009A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one \u3b1-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed. Conclusions: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy

INSIDIOUS RECURRENT ABDOMINAL PAIN

Porphyrias are a group of inherited metabolic disorders of heme biosynthesis leading to excessive accumulation and excretion of porphyrins.The variable clinical manifestations may determine a delay in the diagnosis, followed by a possible negative clinical outcome. We describe a case of a 14-year-old girl with ShwachmanDiamond syndrome (SDS) and epilepsy admitted with severe cyclic abdominal pain not responsive to antalgic therapy, localized in the epigastric area, irradiating to the whole abdomen and the back, associated to aspecific symptoms (diarrhea, fever,vomiting). During hospitalization, the girl was asymptomatic. We excluded infectious, autoimmune, endocrinological causes, a relapse of SDS and performed a screening for porphyria that resulted negative. After each attack, she referred presenting urinary retention followed by hyperchromic urines, anxiety and paresthesias. Past clinical data showed hyponatremia, tachycardia and hypertension. Eventually, increased values of ALA (8.21 mg/l) and PBG (3.96 mg/l) were found; exposure of fresh urines to sunlight caused a change of their color. Finally, genetic analysis was negative. These findings allowed the diagnosis of porphyria, therefore we prescribed a normocalorichyperglucidic diet andpreventive glucose solutions in stressing situations, with regression of symptoms. Acute porphyrias present with life-threatening crisis secondary to the injury of central, peripheral and autonomic nervous system. They can be triggered by drugs, alcohol, infections, reduced caloric intake, endogenous hormone cycles and stressing situations. The characteristic manifestations are severe cyclic abdominal pain, neurological or psychiatric symptoms and/or hyponatremia. Diagnostic is the assessment of plasmatic PBG/ALA, always increased during an attack, normal during remission. Treatment is human haemin although, in mild attacks, a diet with high carbohydrates and/or preventive glucose infusions is effective; a negative genetic evaluation should never exclude the diagnosis. It is important considering acute porphyria in the differential diagnosis of severe cyclic abdominal pain, particularly in subjects affected by different and/or rare clinical disorders

Cerebral Hypoperfusion in Hereditary Coproporphyria (HCP): a Single Photon Emission Computed Tomography (SPECT) study

Hereditary Coproporphyria (HCP) is characterized by abdominal pain, neurologic symptoms and psychiatric disorders, even if it might remain asymptomatic. The pathophysiology of both neurologic and psychiatric symptoms is not fully understood. Therefore, aiming to evaluate a possible role of brain blood flow disorders, we have retrospectively investigated cerebral perfusion patterns in Single Photon Emission Computed Tomography (SPECT) studies in HCP patients

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

BACKGROUND: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. METHODS: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). RESULTS: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. CONCLUSIONS: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

A challenging diagnosis for potential fatal diseases: Recommendations for diagnosing acute porphyrias

Acute porphyrias are a heterogeneous group of metabolic disorders resulting from a variable catalytic defect of four enzymes out of the eight involved in the haembiosynthesis pathway; they are rare andmostly inherited diseases, but in some circumstances, the metabolic disturbance may be acquired. Many different environmental factors or pathological conditions (such as drugs, calorie restriction, hormones, infections, or alcohol abuse) often play a key role in triggering the clinical exacerbation (acute porphyric attack) of these diseases that may often mimic many other more common acute medical and neuropsychiatric conditions and whose delayed diagnosis and treatment may be fatal. In order to obtain an accurate diagnosis of acute porphyria, the knowledge and the use of appropriate diagnostic tools are mandatory, even in order to provide as soon as possible themore effective treatment and to prevent the use of potentially unsafe drugs, which can severely precipitate these diseases, especially in the presence of life-threatening symptoms. In this paper, we provide some recommendations for the diagnostic steps of acute porphyrias by reviewing literature and referring to clinical experience of the board members of the Gruppo Italiano Porfiria (GrIP)