A novel 19‐bp deletion of exon 15 in the <i>HMBS </i>gene causing acute intermittent porphyria associating with rhabdomyolysis during an acute attack

Yrjönen, A.; Pischik, Elena; Mehtälä, Susanna; Kauppinen, Raili

doi:10.1111/j.1399-0004.2008.01061.x

Cited by 13 publications

(14 citation statements)

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“…Identification of disease-specific mutations in the corresponding genes (HMBS, 4 CPOX, and PPOX, respectively) is important for detection and counseling of asymptomatic relatives in families with acute porphyria (1 ). Of the at least 510 mutations that have been identified in these genes (www.hgmd.cf.ac.uk) (3)(4)(5)(6)(7)(8), most are restricted to one or a few families (9,10 ).…”

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confidence: 99%

Diagnostic Strategies for Autosomal Dominant Acute Porphyrias: Retrospective Analysis of 467 Unrelated Patients Referred for Mutational Analysis of the HMBS, CPOX, or PPOX Gene

et al. 2009

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Background: Clinically indistinguishable attacks of acute porphyria occur in acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). There are few evidence-based diagnostic strategies for these disorders. Methods: The diagnostic sensitivity of mutation detection was determined by sequencing and gene-dosage analysis to search for mutations in 467 sequentially referred, unrelated patients. The diagnostic accuracy of plasma fluorescence scanning, fecal porphyrin analysis, and porphobilinogen deaminase (PBGD) assay was assessed in mutation-positive patients (AIP, 260 patients; VP, 152 patients; HCP, 31 patients). Results: Sensitivities (95% CI) for mutation detection were as follows: AIP, 98.1% (95.6%–99.2%); HCP, 96.9% (84.3%–99.5%); VP, 100% (95.7%–100%). We identified 5 large deletions in the HMBS gene (hydroxymethylbilane synthase) and one in the CPOX gene (coproporphyrinogen oxidase). The plasma fluorescence scan was positive more often in VP (99% of patients) than in AIP (68%) or HCP (29%). The wavelength of the fluorescence emission peak and the fecal coproporphyrin isomer ratio had high diagnostic specificity and sensitivity for differentiating between AIP, HCP, and VP. DNA analysis followed by PBGD assay in mutation-negative patients had greater diagnostic accuracy for AIP than either test alone. Conclusions: When PBG excretion is increased, 2 investigations (plasma fluorescence scanning, the coproporphyrin isomer ratio) are sufficient, with rare exceptions, to identify the type of acute porphyria. When the results of PBG, 5-aminolevulinate, and porphyrin analyses are within reference intervals and clinical suspicion that a past illness was caused by an acute porphyria remains high, mutation analysis of the HMBS gene followed by PBGD assay is an effective strategy for diagnosis or exclusion of AIP. .

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confidence: 99%

Diagnostic Strategies for Autosomal Dominant Acute Porphyrias: Retrospective Analysis of 467 Unrelated Patients Referred for Mutational Analysis of the HMBS, CPOX, or PPOX Gene

et al. 2009

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“… 49 The amount of daily fluids may vary from restricted fluid intake in a case of inappropriate antidiuretic hormone secretion to rapid restoration of intravascular volume and correction of electrolyte disturbances in rhabdomyolysis-induced renal failure. 61 Thus, fluid restoration must be tailored individually and careful monitoring of water and electrolyte balance, including sodium, potassium, and magnesium, and renal function should be done ( Table 4 ). Mild to severe hyponatremia is a rather common phenomenon (25%–60%) during an acute attack, 10 , 11 , 50 – 53 and should be corrected slowly (<12 mmol/L/24 h) 61 , 62 because of potential pontine myelinolysis, a condition also described in a patient with AIP.…”

Section: High Carbohydrate Loading and Supportive Treatmentmentioning

confidence: 99%

An update of clinical management of acute intermittent porphyria

Pischik

Kauppinen

2015

TACG

163

186

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Acute intermittent porphyria (AIP) is due to a deficiency of the third enzyme, the hydroxymethylbilane synthase, in heme biosynthesis. It manifests with occasional neuropsychiatric crises associated with overproduction of porphyrin precursors, aminolevulinic acid and porphobilinogen. The clinical criteria of an acute attack include the paroxysmal nature and various combinations of symptoms, such as abdominal pain, autonomic dysfunction, hyponatremia, muscle weakness, or mental symptoms, in the absence of other obvious causes. Intensive abdominal pain without peritoneal signs, acute peripheral neuropathy, and encephalopathy usually with seizures or psychosis are the key symptoms indicating possible acute porphyria. More than fivefold elevation of urinary porphobilinogen excretion together with typical symptoms of an acute attack is sufficient to start a treatment. Currently, the prognosis of the patients with AIP is good, but physicians should be aware of a potentially fatal outcome of the disease. Mutation screening and identification of type of acute porphyria can be done at the quiescent phase of the disease. The management of patients with AIP include following strategies: A, during an acute attack: 1) treatment with heme preparations, if an acute attack is severe or moderate; 2) symptomatic treatment of autonomic dysfunctions, polyneuropathy and encephalopathy; 3) exclusion of precipitating factors; and 4) adequate nutrition and fluid therapy. B, during remission: 1) exclusion of precipitating factors (education of patients and family doctors), 2) information about on-line drug lists, and 3) mutation screening for family members and education about precipitating factors in mutation-positive family members. C, management of patients with recurrent attacks: 1) evaluation of the lifestyle, 2) evaluation of hormonal therapy in women, 3) prophylactic heme therapy, and 4) liver transplantation in patients with severe recurrent attacks. D, follow-up of the AIP patients for long-term complications: chronic hypertension, chronic kidney insufficiency, chronic pain syndrome, and hepatocellular carcinoma.

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“…[5][6][7] No strong temporal association between the onset of rhabdomyolysis and hyponatremia was found in reviewing of the literatures. To date, only 3 cases have been reported in the English literature.…”

Section: The First Reportmentioning

confidence: 99%

“…The management of IBD during pregnancy can provoke a great deal of anxiety in patients and physicians alike. 6,7 IBD gastroenterologists consider terminating the biologics in the first or second trimester so as to minimize placental transfer in the third. These risks and worsening of the IBD are increased by active disease at the time of conception and during pregnancy.…”

Section: The First Reportmentioning

confidence: 99%

“…Compared with age-matched controls, pregnant women with IBD are more likely to have spontaneous abortions, preterm deliveries, and low fetal birth weights. 2,6,7 An important issue that has not been addressed is how to manage recurrence of IBD activity in the third trimester. 1,2 Mounting evidence has demonstrated the relative safety of immunosuppressives and biologics in the treatment of IBD.…”

Section: The First Reportmentioning

confidence: 99%

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R173W Mutation of Hydroxymethylbilane Synthetase Is Associated With Acute Intermittent Porphyria Complicated With Rhabdomyolysis

Chen

Chang

et al. 2015

Journal of Clinical Gastroenterology

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A novel 19‐bp deletion of exon 15 in the HMBS gene causing acute intermittent porphyria associating with rhabdomyolysis during an acute attack

Cited by 13 publications

References 9 publications

Diagnostic Strategies for Autosomal Dominant Acute Porphyrias: Retrospective Analysis of 467 Unrelated Patients Referred for Mutational Analysis of the HMBS, CPOX, or PPOX Gene

Diagnostic Strategies for Autosomal Dominant Acute Porphyrias: Retrospective Analysis of 467 Unrelated Patients Referred for Mutational Analysis of the HMBS, CPOX, or PPOX Gene

An update of clinical management of acute intermittent porphyria

R173W Mutation of Hydroxymethylbilane Synthetase Is Associated With Acute Intermittent Porphyria Complicated With Rhabdomyolysis

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