|Year : 2016 | Volume
| Issue : 1 | Page : 34-38
Congenital erythropoietic porphyria or Günther's disease along with a rare mandibular adenomatoid odontogenic tumor
Kaushal Mahendra Shah, Amol Karagir, Shridevi Adaki
Department of Oral Medicine and Radiology, Bharati Vidyapeeth Deemed University Dental College and Hospital, Sangli, Maharashtra, India
|Date of Web Publication||8-Sep-2016|
Kaushal Mahendra Shah
Department of Oral Medicine and Radiology, Bharati Vidyapeeth Deemed University Dental College and Hospital, Wanlesswadi, Sangli-Miraj Road, Sangli - 416 414, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Congenital erythropoietic porphyria (CEP), or “Günther disease,” is a rare variant of porphyria. It is an autosomal recessive disease caused by deficient uroporphyrinogen III synthase (URO-III-synthase), the fourth enzyme in the heme biosynthetic pathway. We report a case of a young female with the typical clinical presentations of cutaneous photosensitivity characterized by hyper- and hypo-pigmentations, blister formations and scarring of light-exposed skin, mutilation of the toe fingers, dark-purple urine and erythrodontia with pinkish fluorescence under a Wood's lamp. The diagnosis was confirmed by decreased activity of URO-III-synthase in red blood cells and a porphyrin profile compatible with CEP. Presence of adenomatoid odontogenic tumor associated with impacted mandibular right canine was also noted.
Keywords: Adenomatoid odontogenic tumor, autosomal recessive, congenital, erythrodontia, porphyria
|How to cite this article:|
Shah KM, Karagir A, Adaki S. Congenital erythropoietic porphyria or Günther's disease along with a rare mandibular adenomatoid odontogenic tumor. J Indian Acad Oral Med Radiol 2016;28:34-8
|How to cite this URL:|
Shah KM, Karagir A, Adaki S. Congenital erythropoietic porphyria or Günther's disease along with a rare mandibular adenomatoid odontogenic tumor. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2019 May 26];28:34-8. Available from: http://www.jiaomr.in/text.asp?2016/28/1/34/189977
| Introduction|| |
“Porphyria,” a derivative of Greek word, Porphyra, meaning “purple pigment,” is so called due to the purple discoloration of feces and urine when exposed to light in patients during an attack. Felix Hoppe-Seyler in 1871 explained its biochemistry, while Dr. J. H. Schultz is credited with its first description. The porphyrias are a diverse group of rare inherited or acquired disorders of certain enzymes that normally participate in the production of porphyrins and heme. They manifest with either skin problems (cutaneous porphyrias) or neurological complications (acute porphyrias) or occasionally both. Porphyrias are classified physiologically as hepatic or erythropoietic based on the sites of accumulation of heme precursors, either in the liver or bone marrow, and red blood cells (RBCs). The erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth, while the hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain and an acute polyneuropathy). There are eight different subtypes of porphyrias depending on which of the eight enzymes in heme biosynthetic pathway is defective. Gunther classified the diseases of porphyria, including congenital erythropoietic porphyria (CEP), which he called congenital hepatoporphyria, the rarest porphyria. CEP is a rare subgroup with the most severe photosensitivity and mutilation. Typical features also include erythrodontia and dark-purple urine. The diagnosis is made by porphyria profile study and decreased relative enzyme activity.Adenomatoid odontogenic tumor (AOT) is a rare tumor that comprises only 0.1% of all tumors and cysts of the jaws and 3% of all odontogenic tumors. It is a slow-growing benign epithelial odontogenic tumor associated mostly with an impacted maxillary anterior tooth, commonly seen in younger age groups, and having a female predilection. Tumor usually produces a painless asymptomatic sessile swelling, which if surgically enucleated, rarely recurs.
| Case Report|| |
A 15-year-old female patient came to our outpatient department with a concern for her discolored teeth and slowly growing swelling around the right side of the jaw. Mother had noticed that soon after birth, her daughter began to get sunburned easily, with noticeable blister formations on exposed areas which required sun protection. When she was about 1 year old, her urine color changed gradually from red-purple to dark-purple. Her teeth became brownish-purple (erythrodontia) while she was in elementary school, and hypertrichosis developed with irregular hypo and hyper-pigmentation over unprotected skin areas on reaching puberty. Since her secondary school years, she suffered from frequent malaise and anemia with hemoglobin fluctuating between 8 and 11 g%. The patient had a healthy younger brother, no family history of porphyria and no history of consanguinity.
Physical examination revealed extensive brownish-purple blisters and scarring over the face, lips, forehead [Figure 1], ears [Figure 2], mutilation of toe fingers [Figure 3], excessive facial hair, and hypertrichosis of the ears. A diffuse, nontender, firm extra-oral swelling over the right body of mandible was also evident. Intra-oral examination revealed marked cervical generalized purplish pigmentation of the teeth [Figure 4] which fluoresced under ultraviolet light. Porphyria was diagnosed for the cutaneous condition, with consideration of CEP as the possible subtype. Displacement of the mandibular right lateral incisor, first and second premolars, and a missing canine along with a smooth surfaced diffuse round to ovoid swelling with normal appearing overlying mucosa was seen involving the body of mandible, obliterating the mandibular vestibule from lateral incisor to the second premolar. Lymphadenopathy was not evident. Dental findings suggested an odontogenic pathology, and a differential diagnosis of dentigerous cyst, keratocystic odontogenic tumor, calcifying odontogenic cyst and AOT were considered.
|Figure 1: Front profile of the face showing scarring of the forehead and lips|
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|Figure 3: Feet and legs show severely mutilated toe fingers and scars on the legs|
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|Figure 4: Close-up of the teeth shows generalized erythrodontia and sessile diffused swelling in the right mandibular body|
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Orthopantomograph revealed a unilocular radiolucency with a well-defined cortex associated with an impacted mandibular right canine causing displacement and root divergence, but no root resorption of the adjacent lateral incisor and premolars. There was some amount of underlying alveolar bone erosion and thinning of the inferior cortex [Figure 5]. Bilateral carious involvement of mandibular first molars with periapical infection was also seen. Based on the radiographic findings a differential diagnosis of AOT or keratocystic odontogenic tumor was reached.
|Figure 5: Orthopantomograph shows well-defined unicystic radiolucency encompassing an impacted mandibular right canine|
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A hematoxylin and eosin (H and E) staining of the surgically enucleated lesion showed odontogenic epithelial lining arranged in a rosette, ductal and whorled pattern surrounded by fibrous connective tissue capsule, confirming the odontogenic pathology to be an AOT [Figure 6]. Routine hematologic investigation showed decreased RBC values, suggestive of anemia. The porphyrin profile was analyzed through her urine using high-performance liquid chromatography and spectrofluorometry. Urine study showed extremely increased levels of uroporphyrin isomer I and coproporphyrin isomer I, with a lesser degree of elevation in hepta-, hexa- and penta-carboxyl porphyrin (7-, 6-, and 5-COOH porphyrin).
|Figure 6: Histopathologic section of adenomatoid odontogenic tumor showing odontogenic epithelial lining arranged in a rosette, ductal pattern, and surrounded by fibrous connective tissue capsule|
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The preceding history, physical examination, and laboratory findings were in confirmation with the clinical impression of CEP. Patient was advised bone marrow transplantation but refused due to fear of possible complications and accepted avoiding sunlight as the only treatment, as most kinds of sunscreen were ineffective. Patient was advised to wear clothing that would cover the exposed skin parts, in an event of venturing outside, so as to minimize the cutaneous photosensitivity.
| Discussion|| |
The prevalence of all types of porphyria taken together has been estimated to be approximately 1 in 25,000 to 1 in 50,000. Erythropoietic porphyrias are associated with accumulation of porphyrins in erythrocytes and are rare. The rarest is CEP otherwise known as Gunther's disease, with only approximately two hundred patients reported worldwide. CEP is the most mutilating type of the porphyrias seen often during a child's 1st month, with pinkish or brown porphyrin staining of diapers. Severe photosensitivity and easy blister formation after exposure to sunlight then develop in patients with severe forms. Recurrent wound formation, with secondary bacterial infection, may induce milia formation, disfigurement, and even auto-amputation (mutilation) over the digital tips, nose, or ears, while corneal scarring can lead to blindness.
Large amounts of pathogenic porphyrins are excreted in stools and urine, which make the urine dark-purple with pinkish fluorescence. Similarly, brownish-red teeth with porphyrins also emit pinkish fluorescence under a Wood's lamp (erythrodontia), which is a distinctive feature and pathognomonic of CEP. In the bones, fragility and resorption of terminal phalanges may develop. Patients with the severe form will have marked hemolytic anemia and may be transfusion-dependent for life. Secondary splenomegaly may also develop due to the increased uptake of abnormal erythrocytes and this, in turn, may exacerbate the anemia, leukopenia, and thrombocytopenia.
The cause is deficient activity of uroporphyrinogen III synthase (URO-III-synthase) in CEP patients which ultimately leads to accumulation of coproporphyrinogen I, in the bone marrow (normoblasts and reticulocytes), erythrocytes, plasma, bones, and teeth, and undergoes auto-oxidation to the corresponding porphyrins excreted in urine and stools. The urine of our patient showed extremely increased levels of uroporphyrin and coproporphyrin, with lesser elevated 7-, 6-, and 5-COOH porphyrin, as in other case presentations. In addition, the patient had very low URO-III-synthase activity (only 20% of the lower end of normal). This, together with the metabolite elevations and typical clinical presentations, made for a convincing argument for the diagnosis of CEP.
Chronic blood transfusion is effective for some patients by suppressing erythropoiesis and then decreasing porphyrin formation, however, iron overload can be a big problem. Several other treatment modalities have been suggested in previous reports, such as beta-carotene, oral charcoal, and splenectomy, however, with limited success. Stem cell transplantation, which was refused by our patient, is currently the only curative treatment, and several successful cases have been reported. In the past, most CEP patients would not survive beyond the age of 40 years, however, with improvements in supportive care (particularly the use of antibiotics), the prognosis has greatly improved and patients can have an average lifespan of even 60 years although the hematological complications may prove to be fatal. Gene therapy by virus-mediated transfer of functional URO- synthase cDNA into pathogenic hematopoietic stem cells has been reported in a mouse model and may be an important curative methodology in the future. We plan to treat the erythropoietic maxillary anterior teeth with indirect ceramic veneers, rather than performing crown stripping, as the teeth are largely noncarious, while the mandibular first molars will be endodontically treated followed by ceramic crown restorations.
Our patient also presented with an AOT in relation to mandibular right canine. AOT is a relatively uncommon distinct odontogenic neoplasm that was first described by Steensland. Most cases reported are of maxillary canine involvement, however in our case it was seen involving mandibular impacted canine, which is rare. The radiographic findings of AOT frequently resemble other odontogenic lesions such as dentigerous cysts, calcifying odontogenic cysts, calcifying odontogenic tumors, globulomaxillary cysts, ameloblastomas, odontogenic keratocysts, and periapical disease, however displacement of neighboring teeth due to tumor expansion is much more common than root resorptions, as was seen with our case too. Conservative surgical enucleation (performed in our patient too) is the treatment modality of choice, with an excellent prognosis and rare recurrence. However, a routine half yearly clinical and radiologic follow-up will be done. A regular follow-up with a hematologist is also advised, to check for any changes in blood profile, necessitating blood transfusion during a crisis. We hope with the multidisciplinary approach, we will be able to give confidence to the patient and assist in increasing the quality of life and longevity.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]