Puberty Onset Congenital Erythropoietic Porphyria - A Case Report

Sabhiya Majid (1), Qazi Massod Ahmad (2), Iffat Hassan (2),
Syed Nissar (3), Farah Sameena (2), Massarat Rasool (1)
(1) Department of Beiochemistry Government College and Associated Hostpital Srinagar, Jammu and Kashmir, India, (2) Department of Dermatology Government Medical College and Associated Hostpital Srinagar, Jammu and Kashmir, India, (3) Department of Endocrinology S. K. Institute of Medical Sciences Soura, Jammu and Kashmir, India

CASE REPORT

16 year old male, born of consanguineus marriage as full term normal delivery, with normal milestone and development presented with the history of skin lesions on exposed parts of body for the past 2 years and passage of red colored urine for the past 6 months only. Striking features on physical examination were a pinched nose, palor and brownish discoloration of teeth which fluoresced intensely under UV-A light, there was onycholysis of the right little finger. Systemic examination revealed splenomegaly, rest of systemic examination was non contributory. On cutaneous examination hypertrichosis was observed all over the face excepting the periorbital areas. Skin lesions in the form of vesicles, bullae were observed on exposed parts of face, hands and feet. Healing of the lesions occurred with scarring, hyper and hypopigmentation. Milia were present over knuckles with pigmentation in the same area. These symptoms were suggestive of porphyria. Many symptoms of porphyria are very similar to those experienced in other more common diseases, thus laboratory testing based on the definite pattern of accumulation and hyperexcretion of Porphyrins and porphyrin precursor is most effective for diagnosis and typing of porphyrias. This pattern of excretion in turn depends on the defective enzyme of heme biosynthetic pathway and its site of expression. [3,4] Exact porphyrin isomer identification needs sophisticated equipment like HPLC [10,11,15] unavailable in our setup as it is in most hospitals in developing countries. Hence, type of porphyrins increased and not exact isomer was considered. Their preliminary extraction and differentiation by solvent partition was followed by spectrophotometric measurement [3,5,10-16]. Thus investigations included USG abdomen , Chest X-ray, routine hematological and biochemical tests, and the ‘Porphyria profile’ comprising of qualitative and quantitative analysis of porphyrins in urine (24h), stool, plasma and erythrocytes and porphyrin precursors (delta-aminolevaleunic acid and porphobilinogen) in urine.
Routine laboratory investigations significantly revealed decreased Hb (8.0 g/dl), increased reticulocyte count (7% of circulating erythrocytes). In peripheral blood film erythrocytes exhibited anisocytosis, a dimorphic picture (microcytic and normrcytic type ), hypochromia with poikilocytosis. Coombs test was negative. Platelets and WBC were normal. LDH was increased (514 U/l). S. Iron was increased (180ug /dl) with normal total iron binding capacity (350 ug/dl). Liver function tests showed an elevated serum bilirubin with raised alkaline phosphatase levels. All other routine investigations were within normal limits.
As per porphyria profile Porphobilinogen and delta amino levaleunate was absent in urine. Porphyrin levels were raised in urine, stool and blood as observed by bright red fluorescence under Wood’s lamp. Quantitive studies revealed that urinary porphyrins were elevated 50 times than normal (uroporphyrin levels being more than coproporphyrins). Fecal porphyrin levels too were greatly elevated (coproporphyrin levels were higher than uroporphyrins). Erythrocytes showed greatly increased levels of coproporphyrins with much lesser amounts of uroporphyrins, protoporphyrins were negligible. Firm diagnosis was established on the basis of this pattern of increase in porphyrin levels and clinical picture by a systematic ruling out mechanism. The patient was not on any prior medication.

DISCUSSIONS

Congenital Erythropoietic Porphyria (CEP) or Gunther’s disease is an extremely rare, autosomal, recessive, inheritable disorder of heme metabolism. Clinically a non-acute type of porphyria, defect expressed in infancy and is exacerbated by exposure to sunlight. Primary abnormality in CEP is decreased uroporphyrinogen III cosynthase activity primary site of expression of enzymatic defect is the bone marrow resulting in accumulation and hyperexcretion of biologically inactive bone marrow derived type I porphyrins which get distributed throughout the body especially in urine, feces, blood and teeth. By virtue of their phototoxicity these porphyrins accout for multiple pathologies of the integument. Subepidermal bulous lesions progress to crusted erosions which heal with scarring and either hyperpigmentation or rarely hypopigmentation. Repeated damage from secondary infections may lead to epidermal atrophy, pseudoscleroderma, resorption of distal phalanges and severe functional limitations . Facial mutilation especially of the nose and auricular cartilages and ectropion, keratoconjunctivitis and even loss of vision may occur. Hypertrichosis and alopecia are common and erythrodontia is virtually pathognomonic of CEP. Red colored urine may be passed from early childhood. Patients may display signs and symptoms of anemia usually hemolytic with splenomegaly and porphyrin rich gallstones. The spleen is the major site for removal of damaged or hemolysed erythrocytes and splenomegaly frequently observed in CEP is secondary to this process. All CEP patients have increased plasma turnover, erythrocytes exhibit polychromasia, poikilocyatosis, anisocyatosis and basophilic stippling. Incteased reticulocytes and normoblasts may be observed in peripheral circulation. Compensatory expansion of hypertrophic bone marrow may lead to pathological fractures, veretebral compression and collapse. Shortness of stature and rarely osteolytic or sclerotic lesions of skeleton. Onset is in infancy though adult CEP onset too has been very rarely observed. [1-6] The two main differential diagnoses are hepatic erythropoietic porphyria and erythropoietic porphyria in mild cases.
Treatment includes symptomatic measures in form of sun protection, betacarotene, and also splenectomy for intractable. Activated charcoal given by mouth is sometimes effective and Bone Marrow Transplantation is a known cure. [1,2,15,17]

Fig. 1.

Our patient had a history of passage of red colored urine and photosensitivity. Striking features of pinched nose, hypertrichosis of face, with milia, scarring, hypo- and hyperpigmentation of photoexposed parts, resorption of distal phalanges were observed. His teeth, urine, stool and erythrocytes fluoresced intensely under Wood’s lamp. Increase in plasma porphyrins a specific marker for cutaneous porphyrias was observed. Out of cutaneous porphyrias Erythropoietic Protoporphyria was ruled out as urinary porphyrins too are increased. Normal ALA and PBG levels rule out acute porphyrias.The picture of increased urine, stool, plasma and erythrocyte porphyrins on screening was highly suggestive of CEP or a variant Hepato Erythropoietic Porphyria (HEP). [3,4,8,9,15,19]


Fig 2 and Fig 3.

Our patient had greatly increased urinary free porphyrins fluorescing intensely under UV light without extraction which again is a characteristic feature of erythropoietic porphyrias [3-5,15]. Erythrodontia observed is pathognomonic of CEP (Fig 1-3). He had hemolytic anemia with splenomegaly. For establishing a firm diagnosis, quantitative porphyrin studies were used. Urinary Uroporpyrin levels more than coproporphyrins, fecal coproporphyrin levels more than uroporphyrins favor CEP. Erythrocytes having greatly increased levels of coproporphyrins with small amounts of uroporphyrins and negligible protoporphyrins again favoured CEP, as in HEP increased erythrocyte Zn-protoporphyrins are an important feature. Also in HEP, the Zn-porphyrins coming in urine need extraction for detection. [3,4,19]
Thus, with the above mentioned constellation of clinical, hematological and biochemical features, a final diagnosis of puberty CEP onset was entertained and is being reported in view of extreme rarity of this condition.

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