PORPHYRIA by PROFESSOR CHARLES GRAY King's College Hospital Medical School, London
Total Page:16
File Type:pdf, Size:1020Kb
i86 Postgrad Med J: first published as 10.1136/pgmj.32.366.186 on 1 April 1956. Downloaded from PORPHYRIA By PROFESSOR CHARLES GRAY King's College Hospital Medical School, London Three types of porphyria are recognized The involvement of the central nervous system clinically: (i) A congenital, or photo-sensitive, leads to irregularly distributed flaccid paralyses, form, (2) an acute intermittent form and (3) a sometimes involving only a single muscle group, chronic or mixed form. Although on clinical sometimes involving most of the striated muscle of grounds these differ greatly from one another so the body. The clinical picture is very varied, that they have been regarded as distinct diseases, it however, and the neurological features may be now seems possible that this is not so. They are limited to ptosis, a facial palsy, diplopia, disphonia usually regarded as uncommon diseases but it is or dysphasia. Many cases have been erroneously likely that as they become more widely known they diagnosed as hysteria, acute psychosis, polio- will more frequently be recognized. The por- myelitis or encephalitis. These neurological phyrias are characterized by an abnormal excretion manifestations are essentially those of a poly- of porphyrins or of porphyrin derivatives. Normal neuritis and histological studies reveal a patchy urine and faeces contain minute quantities of degeneration of peripheral nerves and anterior porphyrins and only small increases in the horn cells. When the bulbar centres are affected quantities' excreted occur in such conditions as there is early respiratory failure and rapid death.by copyright. pernicious anaemia, liver disease, lead poisoning, On the other hand, if recovery occurs it may be poliomyelitis and various forms of haemolytic remarkably complete even in the most serious anaemia. This. small increase in the normal cases. The immediate prognosis is thus difficult excretion of porphyrins is termed porphyrinuria to assess, although the long-term prognosis is and is not regarded as a primary disturbance of uniformly bad. porphyrin metabolism. In the true porphyrias Hypertension frequently occurs during the acute there is a major abnormality of porphyrin meta- attack but is often labile and then the alternating bolism and there is usually an excretion of periods of hypotension and skin pigmentation abnormal porphyrins or of their derivatives. which is frequently present may lead to anhttp://pmj.bmj.com/ However, in some forms of chronic porphyria erroneous diagnosis of Addison's disease. Oliguria (porphyria cutanea tarda) there is at least a tenfold is a common feature probably because of the and often a thousandfold increase in the excretion restriction of fluid and electrolyte intake which of normal porphyrins. invariably occurs during the acute attack. Waldenstr6m describes a pure abdominal form in which the abdominal symptoms occur without Acute Porphyria involvement of the nervous as well as a system, on September 27, 2021 by guest. Protected In. acute, or acute intermittent, porphyria, nervous form without the abdominal symptoms. characteristic episodes of colicky pain and con- He also describes a comatose form. Photo- stipation are associated with symptoms referable to sensitivity, an essential feature of the other forms the central nervous system. If they are not rapidly of the disease, is rare but when found is mild in fatal the acute episodes may be followed by periods character. of partial or complete remission lasting a variable The urine may be normal in colour but is often time-sometimes a few days but sometimes several dark red or brown especially on standing in light. years. The attacks usually, but not always, begin When freshly passed the urine during the attacks in early adulthood and often seem to be pre- always contains porphobilinogen, a colourless cipitated by the administration of sulphonamides compound readily detected by the chloroform or barbiturates for some incidental condition. The insoluble red pigment formed on adding Ehrlich's abdominal colics may be very severe and simulate a aldehyde reagent. On standing in light, especially surgical emergency such as acute appendicitis, when the reaction is acid, porphobilinogen is con- ileus, cholecystitis, ectopic pregnancy or a twisted verted to a brown pigment, porphobilin, and ovarian cyst but the abdomen is not usually rigid. uroporphyrin III. These two pigments are often Postgrad Med J: first published as 10.1136/pgmj.32.366.186 on 1 April 1956. Downloaded from April 1956 GRAY: Porphyria I87 COOH COOH COOH ICOOH '3I ce 3 - Ha, -- Ha o CO ACI ACID DERIVATIVE t-AMINO_ &iETO &-AMINO LAEVULINIC C CO OOH ADIPIC ACID ACID :ROTOPoRPHYRIN Z· " 4 COOI ' c COOH 0"CH i ___c-__cm COOH coHs E ? CH n . cHo OCOONI|oONOOC-oo COPROPORP:YRmN I CH CH.o by copyright. ea CH, COO" UROPORPHYRIN present in the urine as passed and are responsible and one case studied over a long period of time had for the reddish-brown hue. The porphyrin is lost an eye, both ears and much of the nasal tissue. usually present in the urine as a metal complex, The teeth are red or pink in colour and because of the absorption spectrum of which appears very their high content of porphyrin fluoresce bright similar to that of haemoglobin. Some cases of red in ultra-violet light. At post-mortem the bones http://pmj.bmj.com/ acute porphyria, therefore, have been diagnosed as are found to be similarly impregnated with por- haemoglobinuria. phyrin. The clinical aspects of the condition are identical with those of hydroa oestivali and Congenital Porphyria epidermolysis bullosa but not all patients with one In congenital porphyria a severe photo- or other of these conditions prove to be cases of sensitivity is present at, or soon after, birth. There congenital porphyria. abdominal or central nervous lesions. Associated with this extreme are no system photo-sensitization on September 27, 2021 by guest. Protected The skin exposed to light becomes covered with there is usually haematological evidence of in- bullae, crusts and residual scars. The bullae, creased haemolysis with reticulocytosis, greatly in- which contain serosanguinous or seropurulent creased faecal urobilinogen excretion and some- fluid are succeeded by yellow crusts which times anaemia. Splenomegaly usually develops in gradually turn black and become dense, dry and the second decade of life or sometimes earlier. very adherent. The residual scars may be depressed The urine is cherry red or deep burgundy in and pale with the tissue-paper type of epidermal colour and contains large amounts of porphyrins, atrophy, but later these scars become hyper- mainly uroporphyrin I with smaller quantities of pigmented with loss of hair. Secondary infection coproporphyrin I and other porphyrins. Although leads to gross deformation of the skin and under- the uroporphyrin I sometimes appears as a colour- lying tissues so that the fingers become claw-like less precursor, porphobilinogen is not present and and restricted in movement. The skin around the the Ehrlich test is negative. digits becomes tightly-drawn leading to a false impression of a fusiform thickening around the Chronic Porphyria (Porphyria cutanea tarda) joints. Soft tissue destruction may be extensive In this condition there is a mild photo-sensitivity 188 POSTGRADUATE MEDICAL JOURNAL April I956Postgrad Med J: first published as 10.1136/pgmj.32.366.186 on 1 April 1956. Downloaded from which, however, does not lead to the severe of type I porphyrin are produced in contrast to scarring and deformities characteristic of the con- about 200-300 mg. of type III porphyrins required genital form of the disease. Sometimes there are for synthesis of protoporphyrin for incorporation mild abdominal symptoms but no central nervous in the haem protein. In congenital porphyria there system lesions are present. Exposure to light, heat is a genetically determined abnormality of this or mild trauma leads to a blistering of the exposed enzymic conversion so that the amounts of type I skin. The complexion is usually of a dusky and type III porphyrins are much more nearly bluish-red hue, often with some degree ofmelanosis equal, and the excretion of uroporphyrin I and and hypertrichosis. The condition is often pre- coproporphyrin I in this disease may amount to cipitated by liver disease, either an acute or sub- Ioo mg. or more per day. These type I porphyrins acute hepatitis or cirrhosis. Many cases show no are of no value to the body for synthesis of haem clinical or biochemical evidence of active liver proteins and they are not degraded to bile pigments. disease but are chronic alcoholics. They are therefore excreted or deposited in the During attacks the urine may contain proto- body, in the bones and the teeth. The presence of porphyrin IX or a considerable excess of copro- the free porphyrins in the tissues is known to be as- porphyrin III. Between attacks, however, the sociated with the release of histamine and accounts urinary excretion of porphyrins may be normal but for the photo-sensitivity characteristic ofcongenital a great excess of either copropotphyrin III or porphyria. It is possible that the presence of protoporphyrin IX may be found in the faeces. uroporphyrin I in the red cells may lead to a Often there is a reciprocal relationship between sensitivity of the red cells resulting in the haemo- the urinary porphyrins and faecal porphyrins. lysis which is a characteristic feature of the Apparently in these patients the normal route of condition. The increased haemolysis is usually excretion of these excess porphyrins is via the liver, accompanied by hyperplasia of the bone marrow bile and the gut, but when there is liver damage so that anaemia is rare. The increased synthesis of there is a diversion to the renal route. haem proteins in the bone marrow is, of course, increased of uro- Abnormalities of in accompanied by quantities Porphyrin Biosynthesis porphyrin I which is a by-product of that activity.by copyright.