Portuguese Consensus on Acute Porphyrias: Diagnosis, Treatment, Monitoring and Patient Referral.

Acute porphyrias are a group of rare genetic metabolic disorders, caused by a defect in one of the enzymes involved in the heme biosynthesis, which results in an abnormally high accumulation of toxic intermediates. Acute porphyrias are characterized by potentially life-threatening attacks and, for some patients, by chronic manifestations that negatively impact daily functioning and quality of life. Clinical manifestations include a nonspecific set of gastrointestinal, neuropsychiatric, and/or cutaneous symptoms. Effective diagnostic methods are widely available, but due to their clinical heterogeneity and non-specificity, many years often elapse from symptom onset to diagnosis of acute porphyrias, delaying the treatment and increasing morbidity. Therefore, increased awareness of acute porphyrias among healthcare professionals is paramount to reducing disease burden. Treatment of acute porphyrias is centered on eliminating the potential precipitants, symptomatic treatment, and suppressing the hepatic heme pathway, through the administration of hemin or givosiran. Moreover, properly monitoring patients with acute porphyrias and their relatives is fundamental to preventing acute attacks, hospitalization, and long-term complications. Considering this, a multidisciplinary panel elaborated a consensus paper, aiming to provide guidance for an efficient and timely diagnosis of acute porphyrias, and evidence-based recommendations for treating and monitoring patients and their families in Portugal. To this end, all authors exhaustively reviewed and discussed the current scientific evidence on acute porphyrias available in the literature, between November 2022 and May 2023.

[Diagnosis recommendations for late-onset Pompe disease]. / Recomendações para o diagnóstico da forma tardia da doença de Pompe.

INTRODUCTION: Pompe disease is a progressive and debilitating autossomal recessive myopathy due to mutations in lysossomal acid-α-glucosidase. Its late-onset form has a heterogeneous presentation mimicking other neuromuscular diseases, leading to diagnostic challenge. OBJECTIVE: To develop consensus based recommendations for the diagnosis of late-onset Pompe Disease. MATERIAL AND METHODS: Bibliographic review and analysis of an opinion questionnaire applied to a group of specialists with expertise in the diagnosis of several myopathies and lysossomal storage disorders. Discussed in consensus meeting. RECOMMENDATIONS: Patients with a progressive limb-girdle weakness, fatigue, cramps and muscle pain should be evaluated with CK levels, electromyography, dynamic spirometry and muscle biopsy in inconclusive cases. Suspected cases and those in which muscle biopsy could not allow other diagnosis should be screened for lysossomal acid-α-glucosidase deficiency with DBS (dried blood spot). The diagnosis should be confirmed by determination of lysossomal acid-α-glucosidase activity in a second sample and lysossomal acid-α-glucosidase gene sequencing.

Introdução: A Doença de Pompe é uma miopatia autossómica recessiva progressiva e incapacitante, devida ao défice da enzima lisossómica a-glicosidade-ácida. A sua forma tardia tem uma apresentação heterogénea que mimetiza outras doenças neuromusculares, o que dificulta o diagnóstico. Objectivo: Desenvolver recomendações baseadas em consenso para o diagnóstico da forma tardia da doença de Pompe. Material e Métodos: Revisão bibliográfica e análise de um questionário de opinião aplicado a um grupo de especialistas com experiência no diagnóstico de várias miopatias e doenças de sobrecarga lisossomal. Discussão em reunião de consenso. Recomendações: Doentes com miopatia proximal progressiva, fadiga, cãibras e mialgias devem ser submetidos a uma avaliação complementar com determinação de níveis de creatinina fosfoquinase, electromiograma, espirometria dinâmica e, em casos inconclusivos, biópsia muscular. Nos casos suspeitos ou naqueles em que a biópsia muscular não permita outro diagnóstico deve ser determinada a atividade da enzima lisossómica a-glicosidade-ácida através de teste de gota seca (DBS ­ dried blood spot). A redução da atividade da enzima lisossómica a-glicosidade-ácida requer a confirmação numa segunda amostra e a sequenciação do gene da enzima lisossómica a-glicosidade-ácida.

Extended remission of metastatic epithelioid angiosarcoma of the heart with liposomal doxorubicin.

Angiosarcoma is the most common primary malignant tumour of the heart. It is a rare and aggressive neoplasm that almost always has a short and fatal evolution. By the time it produces symptoms it has usually progressed to a mass causing haemodynamic compromise. Initial presentation with metastatic disease is unusual. We report the case of a 72-year-old man who presented with painful skin lesions on both hands. The skin biopsy was diagnosed as intravascular metastasis of epithelioid angiosarcoma. Body computed tomography scan disclosed a solid mass in the left atrium. The tumour was judged unresectable and the patient was treated with systemic chemotherapy, consisting of liposomal doxorubicin, which resulted in a complete clinical response. The patient remains free of disease after 48 months of follow-up. The excellent clinical evolution of our patient verifies that liposomal doxorubicin may be effective in the treatment of these tumours and significantly prolong patients' lifespan.