Liver transplantation for acute intermittent porphyria:a viable treatment?

BACKGROUND:Acute intermittent porphyria (AIP) is the most common hepatic porphyria.Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms.These symptoms result from the overproduction and accumulation of porphyrin precursors,5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG).The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred.Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks.METHOD:Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database.RESULT:LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks.CONCLUSION:LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.

Novel hydroxymethylbilane synthase gene mutation identified and confirmed in a woman with acute intermittent porphyria:A case report

BACKGROUND Acute intermittent porphyria(AIP)is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase(HMBS)gene.This study aimed to explore the clinical manifestations of a patient with AIP,to identify a novel HMBS gene mutation in the proband and some of her family members,and to confirm the pathogenicity of the variant.CASE SUMMARY A 22-year-old Chinese woman developed severe abdominal pain,lumbago,sinus tachycardia,epileptic seizure,hypertension,and weakness in lower limbs in March,2018.Biochemical examinations indicated hypohepatia and hyponatremia.Her last menstrual period was 45 d prior to admission,and she was unaware of the pregnancy,which was confirmed by a pregnancy test after admission.Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red.Urinary porphyrin test result was positive.Based on these clinical manifestations,AIP was diagnosed.After increasing her daily glucose intake(250–300 g/d),abdominal pain was partially relieved.Three days after hospitalization,spontaneous vaginal bleeding occurred,which was confirmed as spontaneous abortion;thereafter,her clinical symptoms completely resolved.Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10(c.648_651+1delCCAGG)in the proband and four other family members.The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay.CONCLUSION We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.

Diagnosis of acute intermittent porphyria in a renal transplant patient:A case report

BACKGROUND Acute intermittent porphyria(AIP)is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population.AIP is caused by an autosomal dominant-inherited mutation of low penetrance resulting in a deficiency of porphobilinogen deaminase(PBGD)activity.Acute attacks are provoked by stressors such as certain medications,alcohol,and infection.We herein present the first case report of AIP detected in a post-renal transplant patient.CASE SUMMARY The patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephropathy.He subsequently developed diabetes mellitus which required insulin therapy.He had been treated in the recent past with local mesalamine for proctitis.He presented with classic but common symptoms of AIP including intense abdominal pain,hypertension,and anxiety.He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained.His urinary postprandial blood glucose level was 60 mg/24 h(normal,<2 mg/24 h).He was placed on a high carbohydrate diet,and his symptoms slowly improved.CONCLUSION This case report describes a common presentation of an uncommon disease,in which post-transplant complications and medications may have contributed to precipitating the previously undiagnosed AIP.We hypothesize that the lowcarbohydrate diet and insulin with which our patient was treated may have led to the attacks of AIP.Alternatively,our patient’s mesalamine treatment for proctitis may have led to an acute AIP crisis.A high index of suspicion is needed to consider the diagnosis of a heme synthesis disorder,which presents with the common symptoms of abdominal pain,high blood pressure,and anxiety.

Acute Intermittent Porphyria： A Diagnostic Challenge for Endocrinologist

INTRODUCTION Acute intermittent porphyria （AIP） is an autosomal dominant inborn error of metabolism caused by deficiency of porphobilinogen （PBG） deaminase, also known as hydroxymethylbilane synthase （HMBS）, the third enzyme in the heine biosynthetic pathway.