Acute intermittent porphyria is a rare disorder causing neurotoxic precursor accumulation and severe neurological complications. We report a case progressing to tetraplegia and respiratory failure with delayed diagnosis. Treatment with hemin and givosiran resulted in prevention of attacks and functional recovery, highlighting the importance of early diagnosis and long-term therapy.

Acute Intermittent porphyria (AIP) is a rare autosomal dominant disorder of heme biosynthesis characterized by severe acute neurovisceral attacks. Despite available therapies many individuals continue to experience chronic residual symptoms that impair quality of life. Complementary and alternative medicines (CAMs) are widely used in other chronic conditions but their use among individuals with AIP is not well understood. Therefore, we explored patients' experiences through a cross-sectional, anonymous online survey assessing the use and perceived effectiveness of CAMs and cannabis among adults with AIP. Participants were recruited through the Longitudinal Study of the Porphyrias Consortium and a patient advocacy group listserv. Eighty-two individuals (87.8% female; mean age 43.9 ± 13.6 years) completed the survey. Most respondents (92.7%) had experienced acute attacks, and 68.3% reported chronic symptoms such as fatigue (71.4%), muscle weakness (60.7%), and nausea (55.4%). Self-help practices were widely adopted, including meditation (53.7%), relaxation techniques (57.3%), massage (50.0%), and yoga (47.6%), and rated helpful by most users. Chiropractors (17.1%) and acupuncturists (14.6%) were the most frequently visited CAM providers and often reported as being beneficial. Cannabis use was reported by 68.3% of respondents, primarily for symptom management, though perceived effects varied. CAM and cannabis use are prevalent in individuals with AIP to manage persistent symptoms. These findings highlight unmet needs in AIP management and emphasize the importance of further research to evaluate the safety, effectiveness, and integration of CAMs into patient-centered care strategies.

In COVID-associated acute neuropathy with abdominal pain, seizures, hyponatremia, hypertension, or hepatic involvement, suspected acute intermittent porphyria should prompt both early PBG/ALA testing and immediate porphyria-safe medication review to avoid worsening neurovisceral attacks before diagnostic confirmation.

Background: Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria, caused by heterozygous mutations in the HMBS gene. Due to its non-specific clinical manifestations and low clinical awareness among clinicians, AIP is frequently misdiagnosed, leading to significant diagnostic delays and potentially fatal complications. Case presentation: We report a 20-year-old female patient who presented with a 9-month history of recurrent abdominal pain, paralytic ileus, unexplained liver injury, and hyponatremia, followed by progressive limb weakness. She was initially misdiagnosed with Guillain-Barré syndrome (GBS) and received intravenous immunoglobulin and systemic glucocorticoids. However, her condition deteriorated, and she developed life-threatening respiratory muscle paralysis requiring invasive mechanical ventilation. The diagnosis of AIP was confirmed by positive urinary porphobilinogen (PBG) testing and identification of the heterozygous HMBS c.517C>T pathogenic variant. The patient was treated with high-dose carbohydrate loading therapy and comprehensive supportive care, resulting in gradual clinical improvement. Discussion and Conclusions: This case exemplifies the substantial diagnostic challenges associated with AIP, especially when it manifests with peripheral neuropathy that closely mimics GBS. The triad of absent albuminocytologic dissociation in cerebrospinal fluid, preceding visceral symptoms, and inadequate response to standard first-line GBS therapy should immediately raise clinical suspicion for AIP. Enhanced clinical awareness of this rare disorder and timely implementation of urinary PBG screening are of paramount importance to prevent irreversible neurological complications and optimize long-term patient outcomes.

Acute intermittent porphyria is a rare metabolic disorder that often presents with recurrent abdominal pain and nonspecific gastrointestinal symptoms, frequently leading to diagnostic delays in emergency settings. We report the case of a 24-year-old woman with glucose-6-phosphate dehydrogenase deficiency diagnosed at birth and pituitary prolactinoma treated with cabergoline 0.5 mg twice weekly, initiated one month before symptom onset, who presented with recurrent severe epigastric pain and vomiting over the course of one year. Repeated laboratory investigations and contrast-enhanced computed tomography of the abdomen and pelvis were unremarkable, and symptoms required opioid analgesia during multiple emergency department visits. A subsequent metabolic evaluation revealed elevated urinary porphyrin precursors, confirming acute intermittent porphyria. Following diagnosis, the cabergoline dose was reduced to 0.25 mg twice weekly with close monitoring of prolactin levels. During two years of follow-up, she experienced two recurrent attacks that were successfully managed with 2 L of 10% dextrose administered intravenously over three hours, along with opioid analgesia. This case highlights the importance of considering acute intermittent porphyria in patients with recurrent unexplained abdominal pain and emphasizes the possible role of medication-related and endocrine factors as indirect triggers, particularly in resource-limited settings where definitive therapy may not be available.

Porphyrias are rare metabolic disorders caused by inherited or acquired enzymatic defects in the heme biosynthesis pathway, resulting in the accumulation of heme precursors or toxic porphyrin intermediates. The cutaneous porphyrias arise from enzymatic defects in later steps of the heme biosynthesis pathway, which lead to the build-up of photoactive porphyrins in the skin and liver, such as coproporphyrins, protoporphyrins, and uroporphyrins. These photoactive porphyrins generate reactive oxygen species that drive the characteristic cutaneous manifestations, including painful photosensitivity, skin fragility, and blistering. The cutaneous porphyrias encompass both blistering and non-blistering subtypes, which include erythropoietic protoporphyria, X-linked protoporphyria, congenital erythropoietic porphyria, porphyria cutanea tarda, and hepatoerythropoietic porphyria, each distinguished by specific biochemical patterns and clinical features. Acute hepatic porphyrias, which include acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and aminolevulinic acid dehydratase deficiency porphyria, result in the accumulation of neurotoxic precursors, such as δ-aminolevulinic acid and porphobilinogen. While acute neurovisceral attacks predominate in acute hepatic porphyrias, certain subtypes, such as variegate porphyria and hereditary coproporphyria, may present with blistering photosensitivity, creating a significant diagnostic overlap between cutaneous porphyrias and other photodermatoses. This overlap underscores the importance of awareness of acute hepatic porphyrias among dermatologists, who may be the first clinicians to encounter patients with these disorders. In addition, recent treatment breakthroughs will likely bring patients with porphyrias to pursue care, changing the likely underestimated disease prevalence rates. This narrative review provides a comprehensive overview of the pathobiology, clinical features, diagnostic strategies, and management approaches for the cutaneous and acute hepatic porphyrias.

Acute intermittent porphyria (AIP) is a condition characterized by the neurotoxic accumulation of δ-aminolevulinic acid and porphobilinogen. However, chronic kidney disease is an under-recognized complication. A 50-year-old woman experienced recurrent abdominal pain with repeated acute kidney injury and hyponatremia, resulting in a rapid decline in renal function. Marked elevations of both metabolites, as well as her genetic mutation, confirmed AIP. The administration of hemin markedly decreased the frequency of porphyria attacks and significantly attenuated the annual estimated glomerular filtration rate decline. Although the patient eventually developed end-stage kidney disease, hemin treatment slowed the progression of renal failure.

A 21-year-old female patient had recurrent visits to the ED with chest pain managed conservatively, then developed recurrent episodes of seizures and became encephalopathic. She eventually landed in the intensive care unit with extensive investigations to confirm or rule out infective and noninfective etiologies for encephalitis. Her cerebrospinal fluid examination was unremarkable, including autoimmune encephalitis screening. The MRI brain had juxtacortical and in places cortical signal change, with a possibility of an encephalitic process going on. Furthermore, influenza type B was detected on blood screening, and the EEG showed generalized slow-wave discharges. She had dilated pupils, raised blood pressure, and low sodium levels, which pointed toward autonomic instability. Keeping in view autonomic instability, new onset seizures, preceded chest pain, and encephalopathic EEG, she was screened for porphyria and diagnosed with the condition.

The heme synthesis pathway consists of eight enzyme-catalyzed steps, and pathogenic variants in the genes encoding these enzymes cause porphyrias. Diagnosis of certain porphyrias is often significantly delayed, due to their episodic and nonspecific symptoms that mimic more common conditions. To improve genetic diagnostics, which are increasingly used as a first-line approach, the ClinGen General Inborn Errors of Metabolism Gene Curation Expert Panel identified the need to perform gene-disease curations for all genes in this pathway. During this process, we found that several genes (HMBS, UROD, CPOX, and PPOX) had multiple disease assertions, primarily differentiated by dominant versus recessive inheritance. For example, deficiency of HMBS is associated with both autosomal dominant acute intermittent porphyria (AIP) and autosomal recessive homozygous dominant AIP (HD-AIP). Yet, both conditions result from loss-of-function of the HMBS protein, and some recessive cases share identical causative variants with dominant cases. Therefore, our expert panel decided to include patients from both disease assertions (AIP and HD-AIP) as part of a single gene-disease curation rather than separating these groups of patients. This approach correctly links the variable affecting severity to allele dosage. This "lumping" process also required novel parent terms that encompass all disease subtypes and have gene-based nomenclature. Parent terms incorporating both monoallelic and biallelic subtypes were assigned a semidominant inheritance pattern, reflecting the overlapping variants and variable phenotypic severity based on residual enzyme activity. These gene-disease curations for the heme synthesis pathway pave the way for improved downstream variant curation which is a critical requirement to improve porphyria diagnostics. A key focus of this undertaking is to clarify and advance more appropriate nomenclature for these gene-disease relationships, enabling molecular laboratories to report variants in the heme synthesis pathway with greater precision.