Disorders of porphyrin metabolism and their clinical manifestations. Liver in disorders of porphyrin metabolism rank 1990. Disorders of porphyrin metabolism disorders of porphyrin metabolism disorders of porphyrin metabolism fortschr med. Porphyria is a general term for diseases caused by dep osition of intermediate products such as porphyrins in the liver or skin, as a result of congenital or. Heme degradation and disorders of heme degradation ii. If a disorder of porphyrin metabolism is suspected on the basis of symptoms, diagnostic tests are usually ordered of urine and stool and sometimes also of blood and plasma to look for characteristic. Heme and bilirubin metabolism the medical biochemistry page. Structure and nomenclature the basic porphyrin structure consists of four monopyrrole rings connected by methene bridges to form a tetrapyrrole ring figure 331. Endocrine, nutritional and metabolic diseases, and immunity disorders 240279 other metabolic disorders and immunity disorders 270279 277 other and unspecified disorders of metabolism 277. Urine screening for metabolic disorders porphyrin metabolism. Laboratory investigation of the porphyrias sage journals. For claims with a date of service on or after october 1, 2015, use an.
Porphyrins are intermediate molecules in the biosynthetic pathway of heme, a complex molecule that carries oxygen in red blood cells as part of hemoglobin and takes part in liver detoxification reactions. Porphyrins are essential for the function of hemoglobin a protein in your red blood cells that links to porphyrin, binds iron, and carries oxygen to your organs and tissues. Disorders of porphyrin metabolism plastic surgery key. Iron metabolism and disorders of iron metabolism d. Pdf clinically important features of porphyrin and heme.
The porphyrias are caused by inherited defects in the heme biosynthetic pathway that result in excess production of porphyrin precursors. Effective september 1, 20 vitamin or mineral condition. Citations 3 references 88 metabolic diseases of the liver. Altogether 98 patients have been examined, suffering from latent porphyria n 18 and manifest porphyria cutanea tarda n 80.
Most metabolic disorders are genetic, though a few are acquired as a result of diet, toxins, infections, etc. His 1909 seminal work, inborn errors of metabolism, detailed the various inherited metabolic diseases known at the time. Diagnosis of these disorders relies heavily on laboratory investigation. Porphyrins display fluorescence when exposed to ultraviolet light. Cimetidine, which suppresses hepatic alas activity, has been reported to be efficacious to such an extent that it corrects abnormal metabolism 15,16. Disorders of porphyrin metabolism short description. The aetiology, pathogenesis, and clinical features of acute intermittent porphyria are described and discussed with particular reference to the barbiturates. Porphyrias and other disorders of heme synthesis e. In cutaneous porphyria, care should be taken to avoid skin injury and. These disorders are usually inherited, meaning they are caused by gene mutations passed from parents to children. Each of the four authors of this book has a particular interest in disorders of porphyrin metabolism and special experience in their management. Genetic metabolic disorders are also known as inborn errors of metabolism.
As an example of the clinical application of these reference ranges, a case of bronze baby syndrome is discussed. The metabolism of amino acids will be described in the following sequence. They are heterocyclic macrocycles characterised by the presence of four modified pyrrole subunits interconnected at their. Hereditary jaundice and disorders of bilirubin metabolism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in hgexposed adults was not apparent. Garrod 1857 1936, regius professor of medicine at the university of oxford and a consulting physician to st. Overview of porphyrias hormonal and metabolic disorders. Whitley chemistry, tietz textbook of clinicalchemistry, laurence m. Pdf inborn metabolic disorders an update international. Hemecontaining proteins, or hemoproteins, are found extensively in nature.
Department of medicine, university of minnesota, minneapolis, minnesota, usa. Introduction porphyrias are inherited disorders of haem. Start studying chapter 7 disorders of porphyrin metabolism. Bloomer department of medicine, university of minnesota, minneapolis, minnesota, u s a key words. The porphyrias and other disorders of porphyrin metabolism. Quantification of each individual urinary porphyrin enables the diagnosis of certain disorders which otherwise cannot be achieved by the total porphyrin determination.
Porphyrins are a group of organic compounds of which many occur in nature, most wellknown as the pigment in red blood cells. Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Disorders of porphyrin metabolism hematology in clinical. Doctors diagnose porphyrias by measuring porphyrins and porphyrin precursors in the urine. Crohns, granulomatous enteritis, and ulcerative colitis disorders of mitochondrial metabolism chronic liver disease intestinal malabsorption disorders of the biliary tract cystic fibrosis zinc. An inherited defect in an enzyme of heme synthesis results in accumulation of one or more of porphyrin precursors depending on location of block of the heme synthesis pathway. All por phyrias are inherited, with the exception of porphyria cutanea tarda, which is due to an acquired enzyme. The study of disorders of porphyrin metabolism has been mentioned in research publications which can be found using our bioinformatics tool below. Disorders of normal heme synthesis may cause human diseases, including. Fqpps porphyrins, feces porphyrins, quantitative, 24 hour, urinepqnu pqnru porphyrins, quantitative, random, urine.
Disorders of porphyrin metabolism and their clinical. Porphyrin metabolism disorders are grouped into three classes. Each type of porphyria is defined by specific symptoms and diagnostic signs or markers, although these overlap considerably in some types. Disorders msud rare autosomal recessive genetic inherited disorder absence or reduced activity of the enzyme branchedchainketoacid decarboxylase blocking the normal metabolism of the three essential branchedchain amino acids leucine, isoleucine and valine. The acute hepatic porphyrias ahps acute intermittent porphyria aip. Majority of such disorders are due to defects of a single gene that code for enzymes that facilitate conversion of various. Dubinjohnson syndrome is associated with a characteristic accumulation of pigments in the liver and an abnormality of porphyrin metabolism in which over 80 percent of urinary coproporphyrin is coproporphyrin i, as compared with less than 35 percent in normal individuals.
Jan 16, 2016 disorders in heme metabolism porphyria porphyria are rare inherited defects in heme synthesis. Porphyrias oxford academic journals oxford university press. Clinical guide and update on porphyrias gastroenterology. Center for the study of disorders of iron and porphyrin metabolism, university of massachusetts medical center, worcester, massachusetts 01655 search for more papers by this author herbert l. A porphyrin without a metalion in its cavity is a free base. Porphyria porfeareuh refers to a group of disorders that result from a buildup of natural chemicals that produce porphyrin in your body. Pdf bilirubin, which is the principal component of bile pigments, is the end product of the catabolism of the heme moiety of hemoglobin and other. Agedependent reference values of urinary porphyrins in children1. Inborn metabolic disorders imd are a class of genetic diseases involving disorders of metabolism and are congenital.
Symptoms and signs included, at some stage in the course of his. In some porphyria patients and families, however, these diagnostic tools can reveal simultaneous findings that are compatible with 2 different forms of porphyria, a phenomenon referred to as dual porphyria. Clinical problems associated with heme metabolism are of two types. Their individual involvement in the field varies from 12 to 52 years and, combined, represents more than a century of personal experience. Symptomatic patients with porphyria cutanea tarda, a disorder of hepatic porphyrin metabolism presenting as cutaneous photosensitivity, usually have a modest increase in body iron levels that almost always is the result of. The porphyrias are metabolic disorders, primarily inherited, in which the principal features are disturbances of normal heme and porphyrin metabolism. A metabolic disorder is a medical disorder which affects the production of energy within individual animal cells. Abstract an able clinician and an outstanding biochemist have combined their efforts to come forth with an appropriate synthesis of the biochemistry and the clinical aspects of the diseases of porphyrin metabolism.
Porphyrins are the conjugate acids of ligands that bind metals to form complexes. Their bodies have problems making and using heme, a compound made in bone marrow and the liver. Porphyrias are rare disorders that mainly affect the skin or nervous system. Hematological aspects in a case of erythropoietic porphyria. An expert guidelines panel recommended the trace pbg kit thermo tracedma, arlington, tex. Heme is found in hemoglobin, a protein that allows red blood cells to carry oxygen throughout the body. Exam questions disorders of uric acid metabolism disorders of purinespyrimidines metabolism hepatic and cutaneous porpyhrias. Studies of the porphyrias over the past three decades have demonstrated that these diseases arise from biochemical. Disorders that arise from defects in the enzymes of heme biosynthesis are termed the porphyrias and cause elevations in the serum and urine content of intermediates in heme synthesis. People who have these disorders have one thing in common. Disorders of porphyrin metabolism intestinal malabsorption biotin deficiency biotinidase deficiency carnitine deficiency calcium deficiency disorders of calcium metabolism chronic renal disease pituitary dwarfism, isolated growth hormone deficiency hypocalcemia and hypomagnesemia of the newborn. The term inborn errors of metabolism was first coined by archibald e. Clinical medicine of disorders of porphyrin metabolism in man.
In cutaneous porphyria, care should be taken to avoid skin injury and exposure to sun light. Repression of hepatic aminolevulinate synthase by heme and. Specific urine porphyrin profiles are associated with highlevel exposure to mercury, arsenic, lead and some chemicals and drugs. How are disorders of porphyrin metabolism diagnosed. Liver in disorders of porphyrin metabolism liver in disorders of porphyrin metabolism rank, jeffrey m straka, james g bloomer, joseph r. Establish the diagnosis promptly by testing for increased porphobilinogen in a singlevoid urine. Liver in disorders of porphyrin metabolism, journal of. Alad porphyria is a rare recessive autosomal disorder due. Porphyrins in stool and urine in different porphyrias. Many of the porphyrias are inherited as autosomal dominant. Bartholemews hospital and to the hospital for sick children. Consequently, each type of porphyria is characterized by the accumulation of the precursor proximal to the step dependent on the defective. Several diseases unrelated to porphyrias, such as blood disorders, liver disorders, and exposures to toxins such as alcohol, benzene, and lead, may themselves increase the amount of urine porphyrins.
This is followed by a brief description of porphyrin synthesis and the enzymes involved in it, and the distribution of porphyrins and their precursors in certain tissues and biological materials. Badminton and others published the porphyrias and other disorders of porphyrin metabolism find, read and cite all the research you need on researchgate. Chapter 7 disorders of porphyrin metabolism flashcards. If you have porphyria, cells fail to change chemicals in your bodycalled porphyrins and porphyrin precursorsinto heme, the substance that gives blood.
Porphyria is a general term for a group of disorders that affect the skin and nerves. Porphyrin metabolic disorders in porphyria cutanea tarda. There are several types of disorders of porphyrin and heme metabolism. Diagnoses icd10 codes disorders of porphyrin metabolism chlorpromazine e80. Urinary porphyrin excretion in normal children and adults. Additional factors that lead to a critical deficiency in the regulatory pool of heme within hepatocytes determine the disease manifestations 8. Iron metabolism distribution anemias of disordered iron. Figures in parentheses give per cent isomer type iii. Recommended dietary allowance 1015 mg only 1015% is normally absorbed g % hemoglobin 2,5 68 myoglobin 0,15 4 transferrin 0,003 0,1 ferritin, tissue 1,0 27 ferritin, serum 0,0001 0,004 enzymes 0,02 0,6 total 3,7 100 iron distribution. Inherited disorders in bilirubin metabolism lead to hyperbilirubinemia. Chemical injury and disorders of porphyrin metabolism. Clinical pearls vd porphyria cutanea tarda pct inheritance autosomal dominant.
Urine porphyrins abnormal levels of urinary porphyrins, oxidized metabolites of heme biosynthesis, are associated with genetic disorders, metabolic disturbances and diseases, anemias, oxidative stress, and highlevel exposure to toxic chemicals or metals. Group of inherited disorders cha racterized by block in porphyrin synthesis hlack of enzyme in pathway of heme synthesis heme precursors accumulate in tissues excreted in urine andor feces symptoms photosensitivity abdominal pain neuropathy 2 fom sd epn ig a y t defective porphyrin metabolism ep ta ic erythropoietic we will discuss these. Schizophrenic disorders f20 tourettes disorder f95. The types that affect the nervous system are also known as acute porphyria, as symptoms are rapid in onset and short in duration. These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Thus, chronic hepatic porphyria is a porphyrinaccumulation disease, whereas acute hepatic porphyrias are haempathwaydysregulation diseases, characterized. Anemia due to disorders of glutathione metabolism disorders of mitochondrial metabolism vitamin e deficiency inflammatory bowel disease e. Rank, department of medicine, university of minnesota. Pdf porphyria diseases are a group of metabolic disorders caused by abnormal functioning of heme biosynthesis enzymes and characterized. Chronic hepatic porphyrias include porphyria cutanea tarda and. Depending on the type of excess porphyrin produced, patients can experience severe photosensitivity, nerve damage, liver disease, and anemia. Disorders of heme biosynthesis, the porphyrias, present with. Porphyrin metabolism an overview sciencedirect topics.
Porphyrias are disorders of porphyrin metabolism caused by specific defects of enzymes of the heme biosynthetic pathway. Porphyrias represent a group of inherited, or rarely acquired, disorders of porphyrin metabolism, which produce blisters in the skin. Clinically important features of porphyrin and heme metabolism. Mar 30, 2014 disorders of heme synthesis porphyrias are group of inborn errors of metabolism associated with the biosynthesis of heme. Clinical disorders of porphyrin metabolism sciencedirect.
Researched pathways related to disorders of porphyrin metabolism include excretion, pathogenesis, secretion, transport, pigmentation. Inosine uridine role of nucleotides information carriers. This phenomenon is described as secondary porphyrinuria. A large percentage of the aipgene carriers had frequent attacks, severe symptoms, longlasting fatigue and chronic aip and. Demers, reproductive disorders, thyroid disorders, mineralmetabolism, porphyrin. The hepatic and erythropoietic porphyrias are best known of them.
Download the pdf to view the article, as well as its associated figures and tables. Disorders of purine, pyrimidine and porphyrin metabolism. Attachment a icd10 antipsychotic agents for hid use only. Because of the enormous number of these diseases and wide range of systems affected, nearly. It is due to an inherited deficiency of uroporphyrinogen decarboxylase. Deficiency in the activity of one of the enzymes of heme biosynthesis characterizes the various forms of porphyria. Demers mary lee vance, thyroid dysfunction, pituitary disorders, laurence m. Disorders of fatty acid oxidation and mitochondrial metabolism e. Uroporphyrinogen urogen decarboxylase gene on 1p34less common 20% of cases sporadicacquiredmore common prenatal diagnosis dna analysis in familial cases incidence most common porphyria. Clinical medicine of disorders of porphyrin metabolism in. Porphyria cutanea tarda pct is the most common of these disorders, with an estimated incidence of about 125,000 in the united states. A case history of a patient with acute intermitent porphyria is presented.
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