Porphyria attacks in prepubertal children and adolescents.

CONTEXT: The clinical and laboratory features of dominant acute hepatic porphyrias (AHPs) in prepubertal children and adolescents have not been well established. OBJECTIVE: To evaluate clinical and laboratory features of AHPs in prepubertal children and adolescents compared to adults. DATA SOURCES: OVID (Embase Classic+Embase and MEDLINE), Scopus, and Google Scholar. STUDY SELECTION: Studies describing symptomatic children or adolescents (<18 years old) with increased urinary porphobilinogen were included. DATA EXTRACTION: Two reviewers independently extracted the data, with a third reviewer arbitrating discrepancies. RESULTS: 100 studies were included describing 112 patients (26 prepubertal children and 86 adolescents). Differences were found between prepubertal children and adolescents regarding sex distribution (female-to-male ratio: 1:2 vs. 4:1), clinical manifestations, and concomitant clinical manifestations. LIMITATIONS: There was variation in the methods used to diagnose porphyria attacks across studies, and some elements of the quality of individual studies were unclear. CONCLUSIONS: Prepubertal children with AHPs and porphyria attacks presented with distinct demographic and clinical characteristics from adolescents and adults. Nearly two-thirds of the affected children were males, and about half had a concomitant medical condition that can constitutively upregulate hepatic δ-aminolevulinic acid synthase-1. Adolescents were comparable to adults in almost all respects.

Comparison of health behaviours between cancer survivors and the general population: a cross-sectional analysis of the Lifelines cohort.

PURPOSE: To compare the differences in lifestyle behaviours between cancer survivors (CSs) and cancer-free participants in a large and representative population-based cohort. METHODS: We included 115,257 adults from the Lifelines cohort. Cancer status was self-reported, and health behaviours were measured (e.g. body mass index [BMI]) or assessed by questionnaire (e.g. physical activity, smoking, alcohol consumption, sedentary behaviour and diet). The data were then categorised for logistic regression analysis, stratified and adjusted by sex and age (< 55 vs ≥ 55 years). RESULTS: CSs (5473; 4.7%) were diagnosed 9 ± 8.5 years before data collection, were older (mean age 55.4 vs 44.4 years) and more often female (66.6% vs 33.4%) than the cancer-free participants. They were also more likely to be physically active and to have a better diet, and also less likely to be alcohol drinkers; but, were more likely to have a higher BMI, be former smokers and to be sedentary. After adjustment for sex and age, however, BMI was more likely to be normal, physical activity was more likely to be higher and smoking to be prevalent in CSs. Current smoking was also significantly higher among females and those aged < 55 years who were CSs than for those with no history of cancer. CONCLUSIONS: In this population-based cohort, CSs have health behaviour comparable to those without a cancer diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Smoking cessation strategies should target all CSs, but efforts could yield greatest benefit if they target females and those younger than 55 years.

Porphyria-induced posterior reversible encephalopathy syndrome and central nervous system dysfunction.

BACKGROUND AND AIM: An association between neuropsychiatric manifestations and neuroimaging suggestive of posterior reversible encephalopathy syndrome (PRES) during porphyric attacks has been described in numerous case reports. We aimed to systematically review clinical-radiological features and likely pathogenic mechanisms of PRES in patients with acute hepatic porphyrias (AHP) and porphyric attacks. METHODS: PubMed, Scopus, Ovid MEDLINE, and Google Scholar were searched (July 30, 2019). We included articles describing patients with convincing evidence of an AHP, confirmed porphyric attacks, and PRES in neuroimaging. RESULTS: Forty-three out of 269 articles were included, which reported on 46 patients. Thirty-nine (84.8%) patients were women. The median age was 24 ±â€¯13.8 years. 52.2% had unspecified AHP, 41.3% acute intermittent porphyria, 4.3% hereditary coproporphyria, and 2.2% variegate porphyria. 70.2% had systemic arterial hypertension. Seizures, mental changes, arterial hypertension, and hyponatremia occurred more frequently than expected for porphyric attacks (p < .001). Seizures and hyponatremia were also more frequent than expected for PRES. The most common distributions of brain lesions were occipital (81.4%), parietal (65.1%), frontal (60.5%), subcortical (40%), and cortical (32.5%). Cerebral vasoconstriction was demonstrated in 41.7% of the patients who underwent angiography. 19.6% of the patients had ischemic lesions, and 4.3% developed long-term sequelae (cognitive decline and focal neurological deficits). CONCLUSIONS: Brain edema, vasoconstriction, and ischemia in the context of PRES likely account for central nervous symptoms in some porphyric attacks.

Acute Hepatic Porphyrias in Colombia: An Analysis of 101 Patients.

BACKGROUND: There is minimal information available about acute hepatic porphyrias (AHPs) in developing countries. The aim of this study was to describe the demographics, clinical features, and mortality of AHPs in Colombia. PATIENTS AND METHODS: 121 patients with presumed diagnosis of AHPs were reported in Colombia between 1944 and 2018. A pooled analysis of 53 patients with confirmed diagnosis was performed to evaluate the demographics, clinical features, and mortality of AHPs in the country. Selected variables were compared by periods (1952-2000 and 2001-2018). RESULTS: Most attacks occurred in women (66%), with a women-to-man ratio of 39/14. 96% of the patients were diagnosed with AHPs between 15 and 40 years of age. Precipitants were identified in 71% of attacks and more than one precipitant in 41% of them. Drugs (85%) and infections (44%) were the most common precipitants. 11% of women had premenstrual attacks. Abdominal pain was the most common symptom (96%). Cortical blindness, posterior reversible encephalopathy syndrome, and rhabdomyolysis were described. 70% of attacks were confirmed by qualitative test only. 67% of attacks were treated with intravenous heme. The use of heme increased from 4 to 85% in the last two decades. Mortality decreased about twofold in relation to the increase in the use of heme. Severe motor neuropathy was associated with increased mortality. Gonadorelin analogues, heme prophylaxis, and orthotopic liver transplantation have been used to prevent recurrent attacks. CONCLUSIONS: Diagnosis and treatment of AHPs in Colombia have improved in recent decades. However, there are still important shortcomings to address.

El grupo hemo y la ácido aminolevulínico sintasa 1 en la fisiopatología de los ataques agudos de porfiria / The haem group and aminolaevulinic acid synthase-1 in the pathophysiology of acute porphyria attacks

Las porfirias hepáticas agudas son 4 enfermedades raras causadas por deficiencias enzimáticas en la vía biosintética del grupo hemo. Se caracterizan por presentar síntomas neuroviscerales agudos potencialmente letales ante la presencia de factores inductores de la ALAS1. Estos factores pueden ser endógenos o exógenos tales como hormonas sexuales, ayuno, medicamentos, alcohol y tabaco, entre otros. La fisiopatología de los ataques involucra el incremento en la función de la ALAS1, la producción excesiva de precursores de porfirina y la alteración en la síntesis de hemoproteínas por la deficiencia relativa de hemo. En este artículo se revisa la interacción de esos mecanismos con algunos factores inductores, su papel en el origen de los síntomas neurológicos y cómo los tratamientos disponibles bloquean estos procesos (AU)

The acute hepatic porphyrias are a group of 4 rare diseases caused by enzymatic deficiencies in the haem biosynthetic pathway. They are characterized by presenting acute attacks of neurovisceral symptoms in presence of factors that increase the ALAS1 activity. Those factors could be endogenous or exogenous, such as sexual hormones, fasting, drugs, alcohol, tobacco, among other. The physiopathology of the attacks involves an increasing in ALAS1 function, excessive production of porphyrin precursors, and disturbances in hemoproteins synthesis due to the relative haem deficiency. The present paper is a review of the interaction of those mechanisms with some factors that induce ALAS1, their role in the origin of neurovisceral symptoms, and how the available treatments interfere with those processes (AU)