Las porfirinas se pueden detectar en la sangre, la orina o las heces. Aunque no hay cura para la porfiria, puede ser controlada. Referencias American Porphyria Foundation [Internet]. Houston: American Porphyria Foundation; c— About Porphyria [cited Dec 20]; [about 3 screens]. Porphyrins and Porphyria Diagnosis [cited Dec 20]; [about 6 screens].
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See Molecular Genetics for information on allelic variants detected in this gene. Sequence analysis detects variants that are benign, likely benign, of uncertain significance , likely pathogenic, or pathogenic. For issues to consider in interpretation of sequence analysis results, click here. Grimes et al  , Lambie et al  6.
Methods used may include: quantitative PCR , long-range PCR, multiplex ligation-dependent probe amplification MLPA , and a gene -targeted microarray designed to detect single- exon deletions or duplications. Porphyrias with neurologic manifestations are considered acute, because the symptoms occur as discrete, severe episodes. Porphyrias with cutaneous manifestations are considered chronic, because photosensitivity is long standing see Table 3. An earlier British study of individuals with HCP reported similar findings [ Brodie et al ].
Symptoms prior to puberty in individuals who are heterozygous for a CPOX pathogenic variant have never been observed. Fertility and longevity do not appear to be reduced in CPOX heterozygotes. Acute Attacks The initial symptoms of an acute attack are nonspecific, consisting of low-grade abdominal pain that slowly increases over a period of days not hours with nausea progressing to vomiting of all oral intake.
Typically the pain is not well localized but in some instances does mimic acute inflammation of the gallbladder, appendix, or other intra-abdominal organ. In most instances the abdominal examination is unremarkable except for diminished bowel sounds consistent with ileus, which is common and can be seen on abdominal radiography. Typically fever is absent.
In a young woman of reproductive age, the symptoms may raise the question of early pregnancy. Prior to the widespread use of abdominal imaging in the emergency room setting, some individuals with abdominal pain and undiagnosed acute porphyria underwent urgent exploratory surgery.
Thus, a history of abdominal surgery with negative findings was considered characteristic of acute porphyria. A minority of affected individuals has predominantly back or extremity pain, which is usually deep and aching, not localized to joints or muscle groups. Neurologic manifestations. Seizures may occur early in an attack and be the problem that brings the affected individual to medical attention.
In a young woman with abdominal pain and new-onset seizures, it is critical to consider acute porphyria because of the implications for seizure management see Management.
When an attack is unrecognized as such or treated with inappropriate medications, it may progress to a motor neuropathy, which typically occurs many days to a few weeks after the onset of symptoms.
The neuropathy first appears as weakness proximally in the arms and legs, then progresses distally to involve the hands and feet. Neurosensory function remains largely intact. In some individuals the motor neuropathy eventually involves nerves serving the diaphragm and muscles of respiration. Ventilator support may be needed. Tachycardia and bowel dysmotility manifest as constipation are common in acute attacks and believed to represent involvement of the autonomic nervous system.
Of note, when the acute attack is recognized early and treated appropriately see Management , the outlook for survival and eventual complete recovery is good. The mental status of people presenting with an acute attack of porphyria varies widely and can include psychosis. Commonly the predominant feature is distress including pain that may seem hysterical or feigned, given a negative examination, absence of fever, and abdominal imaging showing some ileus only. Incessant demands for relief may be interpreted as drug-seeking behavior.
Because of the altered affect in acute porphyria, it has been speculated that mental illness is a long-term consequence of an attack and that mental institutions may house disproportionately large numbers of individuals with undiagnosed acute porphyria. The experience of those who have monitored affected individuals over many years suggests that heterozygotes who are at risk for one of the acute porphyrias are no more prone to chronic mental illness than individuals in the general population; however, a prospective study is needed.
Kidney and liver disease. In people with any type of acute porphyria, the kidneys and liver may develop chronic changes that often are subclinical. One manifestation of the liver problem is excess primary liver cancer hepatocellular carcinoma. The risk is greatest in women older than age 60 with acute intermittent porphyria fold increased risk above the general population risk ; for men there is a fold increase in risk [ Sardh et al ].
This and the kidney disease may be restricted largely to heterozygotes with chronically elevated plasma or urine delta aminolevulinic acid ALA. Hypertension may be chronic in those with frequent symptoms and may contribute to renal disease.
Circumstances commonly associated with acute attacks are caloric deprivation, changes in female reproductive hormones, and use of porphyria-inducing medications or drugs: Caloric deprivation. Fasting appears to sensitize the heme-synthetic pathway to an inducer, which could be external i. The sensitizing effect of caloric deprivation was demonstrated in the s in experimental animals and has been confirmed by clinical observation.
People who fail to eat because of intercurrent illness or who undertake drastic weight loss are predisposed to an acute attack. First attacks have been reported after reduction gastroplasty for obesity [ Bonkovsky et al ]. CPOX heterozygotes undergoing surgery are at risk because of the routine preoperative fast. This and other anecdotal experience have led to consensus that the first line of treatment for an acute attack is intravenous glucose, which is occasionally helpful.
Changes in female reproductive hormones. A role for female reproductive hormones can be inferred from the fact that acute attacks are infrequent prior to menarche and after menopause. Some women have monthly attacks that appear a few days before the onset of menstruation when progestins peak. Attacks have been linked to use of oral contraceptives; the risk may be associated more with the progesterone component than the estrogen component.
Use of porphyria-inducing medications or drugs. Chronic cutaneous manifestations. Photocutaneous damage is present in only a small minority of those with acute attacks.
Bullae and fragility of light-exposed skin, in particular the backs of the hands, result in depigmented scars. Facial skin damage also occurs, with excess hair growth on the temples, ears, and cheeks; this is more noticeable in women than in men. Threshold for a Pathogenic Effect of Porphyrins and Their Precursors Clinically active acute porphyria is associated with substantial elevation of the precursors ALA and PBG in the blood and urine; the cutaneous porphyrias are associated with increased porphyrins in blood, urine, and feces.
In the acute porphyrias and cutaneous porphyrias, a threshold for symptoms appears to exist. Acute hepatic porphyrias. Urinary ALA excretion increases roughly in parallel.
Chronic cutaneous porphyrias. A threshold has been well defined for porphyria cutanea tarda PCT , in which photosensitivity occurs at values of urine uroporphyrin the predominant pathway intermediate that are more than fold the upper limit of normal.
However, the same is not apparent with regard to urine coproporphyrin: only a minority of CPOX heterozygotes exhibit any photosensitivity. Of note, in individuals with HCP and chronic liver disease the cutaneous component may be more prominent than expected for the observed urine or plasma PBG concentration. Coproporphyrin leaves the plasma largely via the liver going into bile. In chronic liver disease, bile transport processes or bile formation may be impaired, leading to accumulation of coproporphyrin in plasma, which then results in photosensitivity.
Pathophysiology The regulation of heme synthesis differs in liver and in bone marrow, the principal sites of heme production in the body.
The liver is the main source of precursors in the acute hepatic porphyrias: acute attacks are precipitated when environmental factors stimulate increased hepatic heme synthesis and the genetically altered step in heme production becomes rate limiting Figure 1. Heme synthesis in the liver largely serves production of the cytochrome P family of heme-proteins, which are present in high concentration in the liver and have a relatively high turnover rate.
Acute attacks. The precursors ALA and PBG, unlike porphyrins, are colorless and non-fluorescent and do not contribute to photosensitivity in porphyria. Rather, ALA and PBG are highly associated with the neurologic manifestations of acute porphyria and are probably causal, although the mechanism remains speculative. In addition, lead poisoning causes a similar biochemical derangement by binding the sulfhydryls of ALA dehydratase and reducing enzymatic activity; the symptoms in lead poisoning closely mimic those of acute porphyria [ Bissell et al ].
Experimental studies indicate that ALA is a pro-oxidant species that is capable of damaging the inner membrane of mitochondria [ Vercesi et al ]. Liver transplantation has established that this organ is responsible for acute attacks.
Liver transplantation has cured individuals with refractory acute symptoms [ Soonawalla et al ]. Moreover, transplantation of a porphyric liver into a normal recipient in two cases resulted in high circulating levels of ALA and PBG and symptoms of porphyria [ Dowman et al ]. Cutaneous manifestations. Porphyrins are energized by blue light peak wavelength nm. In a test tube, as activated porphyrins relax back to the ground state, the released energy is evident as red fluorescence ca. In vivo, the cycle of light activation and relaxation back to the ground state causes tissue damage, the nature of which varies with the porphyrin.
CPOX pathogenic variants are not clustered around the enzymatic site. Furthermore, no correlation exists between the clinical phenotype and the residual enzymatic activity measured in vitro for a given pathogenic variant [ Lamoril et al ]. Neonatal-onset HCP. In two reported cases, heterozygous but not biallelic CPOX variants have been associated with massive elevation of coproporphyrins, cutaneous blistering, and hemolytic anemia with onset in the neonatal period.
In one case, the pathogenic variant was in exon 6 causing exon 6 skipping. In the other, it was a four-base-pair deletion in exon 7. The clinical picture resembled harderporphyria see Genetically Related Disorders , but fecal analysis indicated HCP markedly increased coproporphyrin and normal harderoporphyrin. Both cases also manifested adrenal insufficiency and hypospadias with a 46,XY karyotype [ Hasegawa et al ]. The reason for the dramatic difference in presentation is unknown.
It has been suggested that adrenal insufficiency is the proximal cause of the neonatal form, perhaps because heme synthesis is regulated by adrenal steroids to a degree that has not been appreciated.
Homozygotes for CPOX pathogenic variants that cause minimal or no symptoms in heterozygotes have very low coproporphyringen-III oxidase activity and a severe phenotype [ Schmitt et al , Hasanoglu et al ] see Genetically Related Disorders. Double heterozygosity for pathogenic variants in genes causing two different types of acute hepatic porphyria. The phenotypes of such double heterozygotes vary but are not necessarily more severe than those associated with heterozygosity for either pathogenic variant alone, suggesting that double heterozygotes for two different types of acute porphyria may not be as rare as has been assumed.
Penetrance Because population studies to determine the prevalence of HCP heterozygosity have not been done, the penetrance of CPOX pathogenic variants is unknown.
Heme production in most heterozygotes appears to be adequate for physiologic homeostasis. Genetic co-factors may also be involved; none has been identified to date. Nomenclature "Coproporphyrinuria" describes urine with an elevated level of coproporphyrin of any cause. Coproporphyria in individuals heterozygous for a CPOX pathogenic variant is referred to as hereditary coproporphyria. Population surveys for CPOX pathogenic variants have not been reported.
Porfiria – Se recomienda una dieta equilibrada
En este diagrama, la madre sufre porfiria. Es portadora de un gen normal y un gen alterado mutado. Por supuesto, en otras familias puede ser el padre quien presente porfiria. Una parte de cada uno de ellos se hereda de cada progenitor. Obviamente, si usted no ha heredado el gen alterado, no puede transmitirlo a sus hijos. En aquellas que lo sufren, parece que son necesarios factores adicionales para que se produzca un ataque. El mejor momento para realizar las pruebas de porfiria es lo antes posible.
COPROPORFIRIA HEREDITARIA PDF
Zulkishura Hereditary pituitary hyperplasia with infantile gigantism. Case histories, radiation treatment data and the proof of porphyria are given in detail. The symptoms are caused by lowered activity of uroporphyrinogen decarboxylase URO-D resulting in accumulation of water-soluble porphyrins in the skin. This treatment has been used to control eclamptic seizures [ Sadeh et al ]. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of r So, combined contraceptive pills are not indicated and progestogen pill must be preferred. Sequencing of the protoporphyrinogen oxidase gene, the gene altered in this type of porphyriarevealed three previously undescribed mutations: Autosomal dominant hereditary ataxia in Sri Lanka. This is a review article of porphyria cutanea tarda addressing pathophysiology, clinical features, associated conditions, triggering factors, biochemistry, histopathology, electronic microscopy, immunofluorescence microscopy and treatment of the disease.
HCP: Coproporfiria hereditaria
The right had a well vascularized scleral graft and rest of the anterior segment was normal. Brain protoporphyrinogen oxidase ciproporfiria was not altered. Full Text Available Acute intermittent porphyria AIP and ichthyosis vulgaris both are autosomal dominant disorders with incomplete penetrance caused by the deficiency of porphobilinogen deaminase enzyme and filaggrin protein, respectively. Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders coproporfiriaa help them make informed medical and personal decisions. We report hereditary pituitary hyperplasia. Treatment of patients with the clinical phenotype of hereditary hemochromatosis is commonly through phlebotomy for removal of excess iron stores. TEM determines the micro splitting level and nature of ultrafine changes in the area of the dermoepidermal junction; at the same time, such tests need special expensive equipment.