Diagnosing and identifying the type of porphyria in a patient requires specialist analysis of porphyrins and/or precursors in blood, urine and faeces. Correct sample storage and handling prior to analysis is essential to minimise preanalytical error.We evaluated the impact of light exposure, time and temperature on erythrocyte and plasma porphyrins in samples from patients with erythropoietic protoporphyria (EPP) and porphyria cutanea tarda (PCT) stored as whole blood for up to 96 hours, and in addition, the effect of freeze-thaw on plasma porphyrins in EPP, PCT and hereditary coproporphyria patient samples.Plasma porphyrins in the EPP patient samples decreased on average by 19% after 6 hours despite light protection and fridge storage, 36% by 24 hours stored light protected at room temperature, 67% within 1 hour when light exposed and 33% after one freeze-thaw cycle. In contrast, plasma porphyrin in PCT samples demonstrated greater stability compared to the EPP samples when stored light protected or exposed at room temperature and during freeze-thaw. Erythrocyte porphyrins in EPP samples were stable for 96 hours under all three storage conditions examined.Erythrocyte protoporphyrin analysis should be undertaken as an additional first-line investigation alongside plasma porphyrin analysis whenever protoporphyria needs to be excluded, due to the significant instability of plasma protoporphyrin.

Acute hepatic porphyria (AHP) constitutes a class of rare diseases caused by reduced function in enzymes of the heme-biosynthetic pathway. AHP includes acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP) and the extremely rare δ-aminolevulinic-dehydrase deficiency porphyria (ADP). This retrospective study describes characteristics of the Danish AHP patient population. Department of Endocrinology at Odense University Hospital serves as national AHP center. We performed a 5-year retrospective description of our AHP cohort using electronic patient journals. We included general symptoms, number of acute attacks, hospitalization rates, long-term sequelae and symptoms, and grouped patients according to creatinine-adjusted urinary baseline excretion (i.e., outside attacks) of the porphyrin precursor porphobilinogen (PBG) in normal-, moderate- and high-excretion and unknown. The cohort contained 129 AHP patients, hereof 100 AIP, 12 HCP and 17 VP. Median age was 46.3 (32.1-62.0) years, and 85 (65.9%) were female. During the 5-years, 38 (29.5%) patients experienced symptoms. Hereof, 20 patients were hospitalized with acute attacks or chronic symptoms and treated with human hemin (n = 14). Most frequently reported symptoms were abdominal pain, nausea, vomiting, and neurological disturbances. Symptoms were more common in patients with high PBG baseline excretion (n = 39) as compared to those with moderate (n = 31) or normal (n = 40) PBG excretion (p = 0.002). Furthermore, females dominated the symptomatic group (68.4%). As reported internationally, AHP is more commonly diagnosed and symptomatic in women, and AIP was the most frequent AHP subtype. Those with an elevated urinary baseline PBG secretion were more likely to report AHP-related symptoms.

Porphyrias constitute a collection of hereditary metabolic disorders arising from disturbances in the enzymatic activities inherent to the heme biosynthetic pathway. Eight subtypes of porphyria, each associated with enzymes in the heme biosynthesis pathway, have been identified. Hereditary coproporphyria is one of the porphyria subtypes characterized by neuropsychiatric clinical features. It develops as a result of a deficiency in coproporphyrinogen oxidase enzyme activity. Consequently, an accumulation of coproporphyrin and its precursor metabolites is observed. Hereditary coproporphyria exhibits autosomal dominant inheritance. Following clinical suspicion, a diagnosis is made with biochemical and genetic tests. The presence of nonspecific symptoms and the lack of consideration for porphyria in differential diagnosis complicate the diagnosis. An 18-year-old male patient was referred to our psychiatry clinic only with psychiatric complaints. The mental status examination revealed affective signs, along with visual hallucinations and delusions. Blood tests and cranial scans at admission showed no abnormalities. After initiating treatment with valproic acid and olanzapine for a presumptive diagnosis of bipolar I disorder, a manic episode with psychotic features, the patient's general medical condition worsened. During clinical observation, the appearance of neurological and gastrointestinal system findings led to a reconsideration of the diagnosis, and porphyria was considered. Urine tests revealed elevated levels of porphyrin intermediates. The diagnosis of hereditary coproporphyria was confirmed by genetic testing, which identified the c.734 C>T mutation in the coproporphyrinogen oxidase gene. Symptomatic relief was observed following a carbohydrate-rich diet without the need for psychotropic treatment. Although their subtypes exhibit distinct clinical features, porphyrias typically present with involvement of multiple systems. Cases that initially present with symptoms specific to a single system can pose diagnostic challenges. In our case report, we aimed to present the psychiatric onset of hereditary coproporphyria, a rare subtype of porphyria known for its potentially fatal attacks when untreated.

Porphyrias are rare genetic disorders caused by heme biosynthesis pathway enzyme mutations, leading to porphyrin precursors build up in various tissues and diverse symptoms. This review centers on acute hepatic porphyrias (AHP). A MEDLINE through PubMed database literature review was conducted. Systematic reviews, clinical trials, cohort studies, case-control studies, expert reviews, and guidelines were preferred for analysis. There are 4 types of AHP: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase deficiency porphyria. These conditions primarily present as neurovisceral attacks, characterized by severe abdominal pain, neuropsychiatric symptoms, or skin lesions, predominantly affecting women aged 15 to 50 years. The diagnostic methods include biochemical tests that assess urinary levels of aminolevulinic acid and porphobilinogen. In addition, measuring porphyrin levels in urine or feces can provide more insights into the type of AHP; however, a definitive diagnosis of the specific type is made through genetic testing. Treatment involves high-glucose diets, intravenous hemin for acute attacks, and givosiran for the prophylaxis of frequent attacks. Liver transplantation remains the only curative option. It is crucial to monitor chronic complications associated with hepatic porphyrias, particularly hepatocellular carcinoma, kidney disease, and arterial hypertension. AHP continues to be an underrecognized condition, warranting consideration in individuals experiencing unexplained abdominal pain, neuropathy, psychiatric symptoms, or skin lesions. There is a need for improved diagnostic techniques and treatment options.

The acute hepatic porphyrias (AHPs) include three autosomal dominant disorders, acute intermittent porphyria, variegate porphyria  and hereditary coproporphyria, and the ultra-rare autosomal recessive 5-aminolevulinic acid dehydratase-deficient porphyria. All four are characterized by episodic acute neurovisceral attacks that can be life-threatening if left untreated. The attacks are precipitated by factors that induce hepatic 5-aminolevulinic acid synthase 1 (ALAS1), resulting in accumulation of the porphyrin precursors, 5-aminolevulinic acid and porphobilinogen, which are believed to cause neurotoxicity. Diagnosis of these rare disorders is often delayed because the symptoms are non-specific with many common aetiologies. However, once clinical suspicion of an AHP is raised, diagnosis can be made by specialized biochemical testing, particularly during attacks. Moderate or severe attacks are treated with intravenous hemin infusions, together with supportive care to relieve pain and other symptoms. Prophylactic treatments are recommended in patients with confirmed recurrent attacks (≥4 attacks in a maximum period of 12 months), the most effective being givosiran, an RNAi therapeutic targeting hepatocyte ALAS1 mRNA. AHP patients with clinically and/or biochemically active disease are at elevated risk for developing long-term complications, including chronic kidney disease, chronic hypertension and hepatocellular carcinoma, thus, surveillance is recommended. Here, using a case-based format, we provide an update on the pathogenesis, diagnosis and treatment of the AHPs based on literature review and clinical experiences.