porphyrias form a group of disorders caused by enzymatic defects in the biosynthesis of haem . haem is required for the synthesis of hemoglobin by erythrocyte precursors in the bone marrow and for the cytochrome p450 enzyme system in liver . the porphyrias are classified into three forms ( on the basis of the predominant site of accumulation of metabolic intermediates ) : hepatic , erythrocytic , and hepatoerythrocytic . congenital erythropoietic porphyria ( also known as gnther disease ) , as the name implies , is an erythrocytic porphyria and it is inherited as an autosomal recessive disorder . despite the limited treatments currently available , the prognosis is not invariably poor and most patients survive to adulthood . a 3-year - old male child , born of consanguineous marriage , presented with blisters on exposed areas since the age of around 6 months . there was hypertrichosis on the shoulders , arms , and face [ figure 1 ] . there were a few intact blisters and crusted lesions on the hands [ figure 3 ] and feet [ figure 4 ] . on the basis of the history of blistering on the exposed areas since early infancy , healing with atrophic scarring , erythrodontia , and red - colored urine , we made a clinical diagnosis of cep . hyperpigmentation of face with hypertrichosis on the forehead and temples blisters on the dorsum of the hands a 13-year - old child , born of consanguineous marriage , presented with photosensitivity and recurrent blistering . , there were severe atrophic scars on the face and exposed parts of the extremities , which had resulted in mutilating deformities of the fingers . hypertrichosis , pigmentation , and milia formation were also present on the face [ figure 5 ] . though erythrodontia was not spotted with the naked eyes , the teeth revealed a pink - red fluorescence under wood 's lamp . histopathological examination of an intact bulla revealed the subepidermal location of the blister [ figure 6 ] . hypertrichosis , pigmentation , milia , and atrophic scars on the face and exposed parts , with mutilating deformities of the fingers photomicrograph showing subepidermal blister ( h and e ; 100 ) a clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity , blistering , and hypertrichosis . routine investigations , including liver and renal function tests , were within normal limits except for mild anemia ( hb 8.0 g / dl , reticulocyte count 7% of circulating erythrocytes ) . on screening with a spectrophotometer , urinary total porphyrin was 1187 nmol / mmol of creatinine ( normal < 35 nmol / mmol ) . the erythrocytic porphyrins showed a level of 124.3 g/100 ml ( reference value less than 40 g/100 ml using the hematofluorometric method ) . a 3-year - old male child , born of consanguineous marriage , presented with blisters on exposed areas since the age of around 6 months . there was hypertrichosis on the shoulders , arms , and face [ figure 1 ] . there were a few intact blisters and crusted lesions on the hands [ figure 3 ] and feet [ figure 4 ] . on the basis of the history of blistering on the exposed areas since early infancy , healing with atrophic scarring , erythrodontia , and red - colored urine , we made a clinical diagnosis of cep . hyperpigmentation of face with hypertrichosis on the forehead and temples blisters on the dorsum of the hands a 13-year - old child , born of consanguineous marriage , presented with photosensitivity and recurrent blistering . , there were severe atrophic scars on the face and exposed parts of the extremities , which had resulted in mutilating deformities of the fingers . hypertrichosis , pigmentation , and milia formation were also present on the face [ figure 5 ] . though erythrodontia was not spotted with the naked eyes , the teeth revealed a pink - red fluorescence under wood 's lamp . histopathological examination of an intact bulla revealed the subepidermal location of the blister [ figure 6 ] . hypertrichosis , pigmentation , milia , and atrophic scars on the face and exposed parts , with mutilating deformities of the fingers photomicrograph showing subepidermal blister ( h and e ; 100 ) a clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity , blistering , and hypertrichosis . routine investigations , including liver and renal function tests , were within normal limits except for mild anemia ( hb 8.0 g / dl , reticulocyte count 7% of circulating erythrocytes ) . on screening with a spectrophotometer , urinary total porphyrin was 1187 nmol / mmol of creatinine ( normal < 35 nmol / mmol ) . the erythrocytic porphyrins showed a level of 124.3 g/100 ml ( reference value less than 40 g/100 ml using the hematofluorometric method ) . a 3-year - old male child , born of consanguineous marriage , presented with blisters on exposed areas since the age of around 6 months . there was hypertrichosis on the shoulders , arms , and face [ figure 1 ] . there were a few intact blisters and crusted lesions on the hands [ figure 3 ] and feet [ figure 4 ] . on the basis of the history of blistering on the exposed areas since early infancy , healing with atrophic scarring , erythrodontia , and red - colored urine , we made a clinical diagnosis of cep . hyperpigmentation of face with hypertrichosis on the forehead and temples blisters on the dorsum of the hands a 13-year - old child , born of consanguineous marriage , presented with photosensitivity and recurrent blistering . , there were severe atrophic scars on the face and exposed parts of the extremities , which had resulted in mutilating deformities of the fingers . hypertrichosis , pigmentation , and milia formation were also present on the face [ figure 5 ] . though erythrodontia was not spotted with the naked eyes , the teeth revealed a pink - red fluorescence under wood 's lamp . histopathological examination of an intact bulla revealed the subepidermal location of the blister [ figure 6 ] . hypertrichosis , pigmentation , milia , and atrophic scars on the face and exposed parts , with mutilating deformities of the fingers photomicrograph showing subepidermal blister ( h and e ; 100 ) a clinical diagnosis of cutaneous porphyria was made on the basis of the severe photosensitivity , blistering , and hypertrichosis . routine investigations , including liver and renal function tests , were within normal limits except for mild anemia ( hb 8.0 g / dl , reticulocyte count 7% of circulating erythrocytes ) . on screening with a spectrophotometer , urinary total porphyrin was 1187 nmol / mmol of creatinine ( normal < 35 nmol / mmol ) . the erythrocytic porphyrins showed a level of 124.3 g/100 ml ( reference value less than 40 g/100 ml using the hematofluorometric method ) . haem is synthesized from glycine and succinyl coa via an eight - step pathway , with each step being catalysed by a separate enzyme [ table 1 ] . accumulation of products of subsequent reactions do not lead to acute attacks but , instead , cause photosensitivity . haem biosynthetic pathway showing the sites of enzyme deficiencies in the different porphyrias clinically , porphyrias are classified as 1 ) acute attacks ( neuropsychiatric ) only , e.g. , acute intermittent porphyria ( aip ) and ala dehydratase deficiency ; 2 ) cutaneous ( photosensitivity ) , e.g. , porphyria cutanea tarda ( pct ) , congenital erythropoietic porphyria ( cep ) , and erythropoietic protoporphyria ( epp ) ; 3 ) both cutaneous disease and acute attacks , e.g. , variegate porphyria ( vp ) and hereditary coproporphyria ( hcp ) . blisters are the presenting features of pct , cep , vp , and hcp , and these constitute the bullous porphyrias . the common features of bullous porphyrias are vesicobullous lesions on photo - exposed parts , hypertrichosis , atrophic scars , hyperpigmentation , milia , and scleroderma - like lesions . porphyrins absorb photons ( light ) of around 408 nm wave length , get excited , and move to higher orbital levels in molecules . the excited electrons return to their normal positions by transferring energy to surrounding structures , thus causing damage . periodine acid schiff ( pas)-positive and diastase - resistant hyaline material is found in the perivascular areas . direct immunofluorescence reveals deposits of igg ( less commonly , igm and complement ) in and around the upper dermal vessels and at the dermoepidermal junction . in most of the other photodermatoses inflammation this severe phototoxicity of porphyrins is used to therapeutic advantage in photodynamic therapy , where porphyrin precursors like aminolevulinic acid or ala ( which gets converted to porphyrins ) is used to cause destruction of tumor and diseased cells . porphyrins chelated with metals like iron , zinc , and cobalt do not show phototoxicity . cep is extremely rare and till recent times less than 200 cases have been reported in world literature . the mutation that causes the most severe deficiency of the enzyme uroporphyrinogen iii synthase is c73r . it results in an increase in uroporphyrin i and coproporphyrin i in plasma , red blood cells , urine , feces , and in different tissues . the clinical spectrum of cep is highly variable and ranges from nonimmune hydrops fetalis as a result of severe hemolytic anemia in utero to late - onset mild cases where the only symptoms are cutaneous lesions in the adult . the presence of large amounts of porphyrins in cep very early in life , at the time of teeth and bone development , results in erythrodontia due to deposition of porphyrins in the developing teeth . the photoactive nature of porphyrin molecules results in the bright pink fluorescence of these pigments in urine , teeth , and bones under wood 's lamp illumination . hemolytic anemia can be mild or severe and may result in gallstones , splenomegaly , osseous fragility , and compression fractures . phototoxicity is characteristically very severe , leading to the formation of blisters and recurrent atrophic scars that result in characteristic mutilation of fingers . epidermolysis bullosa forms a close differential diagnosis due to presence of blistering , scarring , and mutilation . however , in pseudoporphyria , the porphyrin levels in urine , plasma , and stools are not increased . a diagnosis of porphyria can only be made if there is a high index of suspicion in all cases of photosensitivity , abdominal pain , and unexplained seizures . confirmation of the diagnosis of cutaneous porphyria can be made by initial screening of the total porphyrin with a spectrophotometer ( semi - quantitation of porphyrins can be achieved by scanning acidified urine or fecal extracts between 350 nm and 450 nm ) or a spectrofluorometer . the specimens analysed are urine and plasma ( if a spectrofluorometer is available ) or feces ( if a spectrofluorometer is not available ) . the spectrofluorometer is a better instrument as it gives specific curves for vp and epp . next , exact typing of porphyrias can be done with high - pressure liquid chromatography ( hplc ) by identifying the accumulated porphyrins . it is particularly important to distinguish between pct and acute porphyrias like vp and hc which may also present with skin lesions alone . this latter group of patients are at risk of developing life - threatening acute attacks on exposure to the precipitating factors . therapeutic interventions include -carotene to decrease oxidative damage , splenectomy to reduce anemia and thrombocytopenia , transfusion regimens , and intravenous hematin ( oxidized free heem ) therapy to suppress hemoglobin production by a negative feedback mechanism , adsorbents to bind to porphyrins and increase their excretion , hydroxyurea , and corticosteroids . bone marrow transplantation is reported to be successful as it substitutes the erythroblasts of the medulla and produces normal levels of uiiic and reverse the disease manifestations . stem cell transplantation is currently the only known curative therapy and has been successful in a few patients . there are few reports of cep in indian literature.[812 ] the paucity of reports of congenital erythropoietic porphyria in the world literature has prompted us to report these two classical cases .
porphyrias form a group of disorders caused due to defects in the haem synthetic pathway . 
 congenital erythropoietic porphyia ( cep ) is the rarest of the bullous porphyrias ( less than 200 cases have been reported till recent times ) and a clinician may not see a case during his professional life . 
 we present two cases of cep . 
 one child with cep presented with typical infancy - onset blistering , photosensitivity , red urine , and erythrodontia , with hypertrichosis of the upper arms and back . 
 the other child of cep presented with childhood - onset blistering , mutilation , and hypertrichosis on the face .