A case of hereditary coproporphyria with posterior reversible encephalopathy and novel coproporphyrinogen oxidase gene mutation c.863T>G (p.Leu288Trp).

A 21-year-old female had recurrent presentations to the emergency department with myalgia, vomiting, abdominal pain and subsequently developed generalized seizures. She was volume depleted with a plasma sodium of 125 mmol/L (reference interval: 135-145) and she had fluctuating hypertension. Acute porphyria was suspected and confirmed with raised urine porphobilinogen/creatinine ratio of 12:4 µmol/mmoL (reference interval < 1:5) and she was treated with intravenous haem arginate. Urinary porphyrin/creatinine ratio was 673 nmol/mmoL (reference interval <35) and faecal porphyrins 2430 µmol/kg dry weight (reference interval: <200) were markedly elevated, with raised faecal CIII:CI ratio, consistent with acute coproporphyria. Diagnosis was confirmed by the demonstration of a novel missense variant in the coproporphyrinogen oxidase gene c.863T > G (p.Leu288Trp) predicted to be deleterious and which segregated with three other affected family members. Although CT head was normal, magnetic resonance imaging scan revealed symmetrical signal abnormalities and swelling in the parietal and occipital lobes consistent with posterior reversible encephalopathy. Over several days, her seizures ceased and sodium and blood pressure normalized. The aetiology of the acute porphyric attack was likely multifactorial with contributions from a recent viral illness and caloric deprivation. No drug precipitant was identified. We postulate that untreated hypertension played a key role in the development of posterior reversible encephalopathy. Early clinical suspicion and urine porphobilinogen testing are the key components in preventing morbidity and mortality in acute porphyrias.

Liver failure after Hydroxycut™ use in a patient with undiagnosed hereditary coproporphyria.

We report the case of a young male presenting with cholestatic liver failure. After an extensive workup, the etiology of the liver failure was determined to be due to hereditary coprophorphyria (HCP). The inciting event was the use of Hydroxycut™, an over-the-counter supplement to promote weight loss that has been reported to cause oxidative liver injury in vulnerable populations. Although HCP is a rare cause of cholestatic liver failure, it is treatable if diagnosed correctly and in a timely manner. In this clinical vignette, we discuss a case that highlights the genetic susceptibility to disease that can be unmasked by environmental exposures. We also review the relevant literature on Hydroxycut™ and how it can affect hepatic function.

A challenging diagnosis for potential fatal diseases: recommendations for diagnosing acute porphyrias.

Acute porphyrias are a heterogeneous group of metabolic disorders resulting from a variable catalytic defect of four enzymes out of the eight involved in the haem biosynthesis pathway; they are rare and mostly inherited diseases, but in some circumstances, the metabolic disturbance may be acquired. Many different environmental factors or pathological conditions (such as drugs, calorie restriction, hormones, infections, or alcohol abuse) often play a key role in triggering the clinical exacerbation (acute porphyric attack) of these diseases that may often mimic many other more common acute medical and neuropsychiatric conditions and whose delayed diagnosis and treatment may be fatal. In order to obtain an accurate diagnosis of acute porphyria, the knowledge and the use of appropriate diagnostic tools are mandatory, even in order to provide as soon as possible the more effective treatment and to prevent the use of potentially unsafe drugs, which can severely precipitate these diseases, especially in the presence of life-threatening symptoms. In this paper, we provide some recommendations for the diagnostic steps of acute porphyrias by reviewing literature and referring to clinical experience of the board members of the Gruppo Italiano Porfiria (GrIP).

Lamotrigine in the treatment of psychotic depression associated with hereditary coproporphyria -- case report and a brief review of the literature.

OBJECTIVE: We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. CASE REPORT: M.F., a 38-year-old, single woman was admitted to an acute psychiatric ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was diagnosed 9 years before the current admission. While on treatment with olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view of her significant mood fluctuations predominantly with depressed phases, lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow-up, while still on lamotrigine, her porphyria was asymptomatic. CONCLUSION: To the best of our knowledge, this is the first report about the safe administration of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute porphyric attack as confirmed by clinical and laboratory findings.

Kidney transplantation in hereditary coproporphyria using tacrolimus and mycophenolate mofetil: a case report.

BACKGROUND: The porphyrias are a group of disorders of the heme biosynthesis pathway that may present with acute life-threatening attacks, commonly exacerbated by a wide variety of medications. Many newer immunosuppressive medications, which are in use following kidney transplantation, have not been fully explored in acute porphyrias. CASE REPORT: A 53-year-old woman received a kidney from a deceased donor, after being on hemodialysis for 4 years. Hereditary coproporphyria was diagnosed at age 19 years. We administered tacrolimus, mycophenolate mofetil and steroid immunosuppression. In the immediate post-transplant periods she displayed abdominal pain and transient uroporphyrin elevation in parallel with slightly elevated (15 ng/mL) tacrolimus concentrations. As the target tacrolimus level was achieved, these findings disappeared. CONCLUSIONS: Tacrolimus, mycophenolate- mofetil, and steroid therapy for hereditery coproporphyri was safe, in the long term.

Co-existence of hereditary coproporphyria and porphyria cutanea tarda: The importance of genetic testing.

The porphyrias are a group of inherited disorders that result in defects in the enzymes of the haem biosynthetic pathway, causing photosensitive bullous skin eruptions or abdominal and neurological attacks. Enzymatic defects result in specific porphyrin excretory patterns that are diagnosed biochemically and can be confirmed by genetic testing. Defects in the coproporphyrinogen oxidase (CPOX) enzyme result in the autosomal dominant hereditary coproporphyria. Multiple mutations have been identified in the CPOX gene and incomplete penetrance is noted. Latent carriers without clinical evidence of disease are at risk of life-threatening attacks. Porphyria cutanea tarda may be inherited, but is more commonly acquired. Occasionally two forms of porphyria may co-exist. The importance of genetic testing is discussed.

Cerebral vasospasm and anterior circulation stroke secondary to an exacerbation of hereditary corproporphyria.

Acute porphyria, though rare, has well-known neurological sequelae. Vasospasm rarely complicates exacerbations of acute intermittent porphyria, but has not been previously reported in hereditary coproporphyria. We describe a porphyric crisis in a woman with previously undiagnosed hereditary coproporphyria (triggered by rifampicin), leading to vasospasm and stroke.

Syndrome of inappropriate antidiuretic hormone secretion associated with coproporphyria: case report and review of literature.

OBJECTIVE: To remind physicians to consider the hepatic porphyrias in the differential diagnosis of the syndrome of inappropriate antidiuretic hormone secretion. METHODS: We present a case report of a patient seen in the hospital for severe hyponatremia, who was discovered to have the syndrome of inappropriate antidiuretic hormone secretion attributable to coproporphyria. Results of laboratory tests of the patient and her family are presented. RESULTS: A 54-year-old woman was seen in the hospital because of severe hyponatremia accompanied by generalized seizures. Her serum sodium concentration was 112 mEq/L, with concomitant serum and urine osmolalities of 235 and 639 mOsm/kg, respectively. Renal, thyroid, and adrenal functions were normal. Brain, chest, abdominal, and pelvic imaging studies were negative for occult malignant disease. Urinary excretions of porphobilinogen and aminolevulinic acid were substantially elevated. Results of follow-up urine, plasma, and fecal porphyrin studies were consistent with coproporphyria. Results of porphyrin metabolic studies of the patient's family showed normal findings in her parents and a minimally increased fecal coproporphyrin concentration and urinary uroporphyrin excretion in her sister. CONCLUSION: An endocrinology consultation is often requested for patients with hyponatremia. It is important to consider the acute hepatic porphyrias in the differential diagnosis, even though these are rare disorders and the family history may not always be helpful because of the high frequency of asymptomatic carriers.

Solar urticaria and porphyrias.

The importance of disturbances of porphyrin metabolism in solar urticaria is discussed. 15 cases of porphyrias with sun sensitivity are presented comprising 5 cases of erythropoietic protoporhyria, 8 cases of coproporphyria hereditaria and 2 cases of porphyria variegata, 9 out of these 10 patients presented neuroabdominal symptoms and in 4 cases contraceptive pills have triggered the disease. Due to the risk of severe forms of disease sometimes drugs induced porphyrias must be considered in all cases of solar urticaria and a correct laboratory study done in the suspected cases.