DOCSLIB.ORG

Hepatoerythropoietic Porphyria: Neuroimaging Findings

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Hepatoerythropoietic Porphyria: Neuroimaging Findings Hepatoerythropoietic Porphyria: Neuroimaging Findings Juan Berenguer, Jordi Blasco, Carlos Cardenal, Teresa Pujol, M. J. Cruces Prado, Carmen Herrero, Jose´ M. Mascaro´, C. de la Torre, and Jose´ M. Mercader Summary: CT and MR findings in two patients with hepatoeryth- months later (Fig 1) showed cortical atrophy, located ropoietic porphyria are presented. CT scans showed atrophy and mainly in the frontal lobes, with associated parenchyma- cortical mineralization at the same level. MR examination performed tous calcifications at the same level. No abnormal contrast in one of the two patients showed mainly frontal cortical atrophy enhancement was detected. and punctate bright signal on T1- and T2-weighted sequences. An MR examination 1 year later revealed the same frontal atrophy seen on the CT scans, as well as punctate Index terms: Brain, metabolism; Degenerative disease bright signal on T1-weighted images at the same level as the parenchymatous calcifications shown on the CT study. Porphyria is a hereditary disorder character- Several focal areas of high-signal change on T2-weighted ized by enzyme defects in heme biosynthesis, images were visible in the region of the bifrontal calcifica- and can affect the central nervous system tions. No other parenchymatous alterations of interest (CNS) (1–4). We describe two patients with were found (Fig 1B and C). A CT scan 4 years later showed progression of the hepatoerythropoietic porphyria (HEP) who had atrophy, possibly due to the antiepileptic treatment, with cortical atrophy and frontal mineralization on no change in the number or morphology of the calcifica- computed tomographic (CT) and magnetic res- tions (Fig 1D). onance (MR) studies of the brain. Case 2 Case Reports A 21-year-old man had experienced severe photosen- Two unrelated patients with clinical features and labo- sitivity since infancy with the same cutaneous lesions as ratory findings of HEP experienced several seizures during the patient described in case 1. His enzymatic alterations, follow-up. CT and MR examinations were performed to with increased levels of uroporphyrin and 7-carboxylic clarify the pathogenesis of the seizures. Dermatological, porphyrins in the urine and elevated quantities of iso- biochemical, and genetic aspects of both patients have coproporphyrin in the feces and protoporphyrin in the been published previously (3, 5–7). erythrocytes, pointed to the diagnosis of HEP. The diag- nosis was confirmed when values lower than 18% of nor- Case 1 mal were found in the enzyme erythrocyte uroporphyrino- gen decarboxylase. Treatment with cutaneous protecting A 28-year-old woman had had progressive photosen- substances was initiated at that time. sitivity since the age of 1 year, with hypertrichosis, scars, At the age of 21 years, he began to experience several blisters, and sclerodermoid changes. Laboratory findings episodes of seizures with no evidence of precipitating fac- showed an increase in uroporphyrin and 7-carboxylic por- tors. These seizures required pharmacological treatment phyrins in the urine, with elevated levels of isocopropor- with carbamazepine. A CT examination showed cortical phyrin in the feces, and protoporphyrin in the erythrocytes. atrophy, mainly in the frontal lobes, with associated par- The activity of the erythrocyte uroporphyrinogen decar- enchymatous mineralization (Fig 2). boxylase was decreased to 10% of normal values. These enzymatic features confirmed the diagnosis of HEP, and treatment with cutaneous protecting substances for exter- Discussion nal application was begun. At the age of 23 years, the patient experienced a pos- Porphyria cutanea tarda (PCT) is the most terior generalized focal seizure. A CT study performed 4 common form of porphyria and is caused by a Received April 16, 1996; accepted after revision October 31. From the Departments of Radiology (J.Be., J.Bl., C.C., T.P., J.Me.) and Dermatology (C.H., J.Ma.), Hospital Clinic i Provincial de Barcelona, Universitat de Barcelona, and the Department of Dermatology, Hospital Provincial de Pontevedra (M.J.C.P., C.D.L.T.), Spain. Address reprint requests to Juan Berenguer MD, Department of Radiology, Section of Neuroradiology, Hospital Clinic i Provincial de Barcelona, Villarroel, 170 E-08036 Barcelona, Spain. AJNR 18:1557–1560, Sep 1997 0195-6108/97/1808–1557 © American Society of Neuroradiology 1557 1558 BERENGUER AJNR: 18, September 1997 Fig 1. Case 1. A, Noncontrast axial CT scan obtained at the age of 23 years shows bifrontal cortical calcifications (arrows) and diffuse atrophy, predominantly frontal. Contrast-enhanced CT scan (not shown) displayed no enhancing lesions. B and C, MR studies performed at the age of 24 years, after a year of antiepileptic treatment. Sagittal T1-weighted spin-echo image (560/20/1 [repetition time/echo time/ excitations]) (B) shows punctate bright signal (arrow) at the same level as the frontal calcifications found on the CT scan. Note cerebral atrophy, mainly in the frontal lobes. Axial T2-weighted spin-echo image (2500/100/1) (C) shows small nodular hyperintense areas at the cortical-subcortical level (arrows). D, CT scan at the age of 28 years shows progressive atrophy and no significant changes in either the number or size of the calcifications (arrows). The patient had been receiving antiepileptic treatment since the age of 23 years. At the time of the CT studies she was in an intercrisis period. reduction in uroporphyrinogen decarboxylase are clinical symptoms typical of acute intermit- activity. Two types of PCT have been described: tent porphyria (10), and they are also frequently the sporadic form, in which the uroporphyrino- seen with hereditary coproporphyria and varie- gen decarboxylase activity in the hepatocytes gate porphyria (8). Increase of the porphyrin falls by 50%, and the familial form, in which precursors d-aminolevulinic acid and porphobi- other cell types, such as erythrocytes, are also linogen may be observed in urine during the affected by the enzymatic defect. HEP, de- attacks. Neurologic manifestations are caused scribed by Pin˜ol et al (5) in 1975, is considered by the excessive presence of porphyrins (4). to be the homozygous form of PCT. In HEP, Previous reports of the neuroimaging aspects hematologic and severe cutaneous manifesta- of porphyria include a case of intracranial cal- tions appear from infancy as a result of deficient cifications located on the dura mater and cal- uroporphyrinogen decarboxylase activity (3, 6, varia in a patient with congenital erythropoietic 8, 9). porphyria (Gunther disease) (2). MR changes Neurologic manifestations, such as abdomi- after paramagnetic contrast administration, nal pain, neuritis, seizures, encephalopathy, de- with multiple areas of bright signal on T2- pression on the conscious level, and psychoses, weighted sequences (1, 4, 9–11) and diffuse AJNR: 18, September 1997 HEPATOERYTHROPOIETIC PORPHYRIA 1559 gyriform enhancement on T1-weighted se- weighted images. Hyperintensities on T2- quences (1, 4, 10), have been reported in pa- weighted images were also seen, and probably tients with acute neurologic symptoms of por- corresponded to the encephalomalacic areas. phyric encephalopathy. These MR changes Cortical calcifications and seizures can be may be caused by a transient vasoreactive isch- seen in many diseases. In phakomatoses, such emia due to a reversible vasculopathy (1, 4, 10, as Sturge-Weber syndrome (12, 13), calcifica- 11). Transient diffuse vasospasm at MR angiog- tions are located mainly in the occipital lobes, raphy has been described in one case of por- and contrast enhancement usually occurs (13). phyric encephalopathy (4). The pathogenesis Epilepsy and brain calcifications can also be of vasospasm is unknown, but it may be asso- seen in coeliac disease (14), in tuberous scle- ciated with a decrease in nitric oxide synthase rosis (15), in association with open heart sur- enzyme activity when there is a heme defi- gery (16), and in relation to “cerebral steal” ciency, as in acute intermittent porphyria. Be- phenomenon from an arteriovenous malfor- cause nitric oxide is an important CNS vascular mation (17). Other possible origins of brain cal- dilator, its deficit could be related to vasocon- cifications, such as radiation therapy (18), striction and ischemic lesions (10). Other pos- tuberculosis, purulent meningitis (19), lupus sible explanations for the neurologic lesions in erythematosus (20), Prader-Willy syndrome patients with porphyric encephalopathy include (21), osteopetrosis (22), pseudohypoparathy- neurotoxic effects due to excessive porphyrin roidism (23), congenital cytomegalovirus (24), and/or intracellular heme deficiency in neural and cerebral infarction (25), have also been tissues (1). Other MR changes, such as areas of documented. bright signal in the posterior cord in a patient None of these other causes of cerebral calci- with hereditary coproporphyria (9), have also fications were present in either of our patients. been documented. We do not think that the calcifications were Our two patients experienced several epi- associated with the cutaneous protecting sub- sodes of generalized seizures. A CT examina- stances used externally or with the antiepileptic tion of the brain performed several months after medication, since these treatments were initi- the seizures showed cerebral cortical atrophy ated a few weeks before CT was performed. We located mainly in the frontal lobes with associ- believe that both the calcifications and the hy- ated parenchymatous cortical calcifications.
Load more

Recommended publications
  • Aborted Sudden Death in a Young Male SELF ASSESSMENT
    664 Postgrad Med J 2003;79:664–666 Postgrad Med J: first published as 10.1136/pmj.79.937.666 on 3 December 2003. Downloaded from SELF ASSESSMENT ANSWERS Aborted sudden death in a Q2: What is the pathophysiological basisofthiscondition? What further young male diagnostic tests would you consider doing in this patient? Q1: What is the ECG (fig 1; p 660) Genetic studies have shown that Brugada diagnosis? Why is it important to syndrome and chromosome 3-linked long QT recognise this condition? syndrome (LQT3) are allelic disorders of the The ECG done on his arrival at the emergency cardiac channel gene (SCN5A, 3p21). The room (see questions) shows (i) sinus tachy- inheritance is autosomal dominant with cardia, (ii) a QRS complex that ends with a variable penetrance. The SCN5A gene codes positive deflection (or prominent J wave) for the alpha subunit of the sodium channel. that is, a rsR9 pattern in V1 and V2, and (iii) Mutations of this gene results in abnormal- an elevated downsloping ST segment ending ities of the sodium channel, with abnormal in a small negative T-wave deflection. This ion conductance patterns and can be demon- ECG pattern in someone with a history of strated in up to 25% Brugada syndrome syncopy and documented ventricular fibrilla- cases.235 Brugada-type downsloping ST seg- tion/aborted sudden death, is most consistent ment is a normal feature of the ECG in some with the eponymous Brugada syndrome. rodents, whereas in higher mammals, the ST Described first in 1992 by Brugada and segment is usually isoelectric in the normal Brugada, Brugada syndrome is an inherited state.
    [Show full text]
  • Splenectomy for HIV-Related Immune Thrombocytopenia Comparison with Results of Splenectomy for Non-HIV Immune Thrombocytopenic Purpura
    ORIGINAL ARTICLE Splenectomy for HIV-Related Immune Thrombocytopenia Comparison With Results of Splenectomy for Non-HIV Immune Thrombocytopenic Purpura Reginald V. N. Lord, FRACS; Maxwell J. Coleman, FRACS; Samuel T. Milliken, FRACP Objective: To determine the effectiveness and safety of tomy, with an elevation of the platelet count to greater splenectomy for patients with human immunodefi- than 1003109/L. After a median follow-up of 26.5 months, ciency virus (HIV)–related immune thrombocytopenia, all but 1 patient had a sustained complete remission with using the results of splenectomy for patients with non- no need for medical therapy for thrombocytopenia. Sple- HIV immune thrombocytopenic purpura as a control nectomy was more effective in the HIV-related throm- group for comparison. bocytopenia group than in the non-HIV immune throm- bocytopenic purpura group, with significantly higher Design: Retrospective study. platelet counts at 1 week and 1 month after splenec- tomy in the HIV group (t test, P=.02 and P=.009, respec- Setting: Tertiary care university hospital. tively). There were significantly fewer patients needing medical therapy for thrombocytopenia after splenec- Patients: Fourteen patients who underwent splenec- tomy in the HIV group (x2 test, P=.02). There were no tomy for symptomatic, medically refractory HIV- remarkable short- or long-term complications in the pa- related immune thrombocytopenia at this hospital from tients with HIV infection, including no overwhelming 1988 to 1997. During the same period, 20 patients had postsplenectomy infections. Three patients have died, and splenectomy for treatment of non-HIV immune throm- 2 patients have developed AIDS since operation. bocytopenic purpura.
    [Show full text]
  • Porphyria Cutanea Tarda in a Swedish Population: Risk Factors and Complications
    Acta Derm Venereol 2005; 85: 337–341 CLINICAL REPORT Porphyria Cutanea Tarda in a Swedish Population: Risk Factors and Complications Ingrid ROSSMANN-RINGDAHL1 and Rolf OLSSON2 Department of 1Dermatology, and 2Internal Medicine, Sahlgrenska University Hospital, Go¨teborg, Sweden There are varying reports on the prevalence of risk factors identified (Human Gene Mutation database: www. in porphyria cutanea tarda (PCT). We reviewed 84 uwcm.ac.uk/uwcm/mg/hgmd0.html) (2). patientswithPCTinarestricteduptakeareain Additional genetic or non-genetic factors are needed Gothenburg, Sweden and evaluated different potential for overt disease. Known provoking factors are iron, risk factors for the disease and complications. Besides a alcohol, oestrogen and hepatotropic virus infection such thorough medical history, the patients were investigated as hepatitis C virus (HCV), all of which are associated with urinary porphyrin analyses, transferrin saturation, with inhibition of hepatic UROD activity (3–5). Reports ferritin and liver tests. Subsamples of patients were tested from different countries vary widely regarding the for antibodies to hepatitis C virus (n568), haemochroma- importance of different factors for the induction of the tosis gene mutations (n558) and with the oral glucose disease. For example, reports from southern Europe (6, tolerance test (n531). We found a prevalence of about 1 7), Japan (8) and the USA (5, 9) indicate a very great patient with PCT in 10 000 inhabitants. Nineteen (23%) importance of HCV for the phenotypic expression of patients reported heredity for PCT. Identified risk factors PCT, with figures varying between 56% and 85%. This is were alcohol abuse (38% of male patients), oestrogen in contrast to northern France (10), Germany (11), treatment (55% of female patients), anti-hepatitis C virus Czechoslovakia (12) and New Zealand (13), where PCT positivity (29% of male patients), diabetes (17%) or is less often associated with HCV (positivity rates impaired glucose tolerance (45% of tested patients) and varying between 0 and 23%).
    [Show full text]
  • TSC Facts Countdown for 15 Days in May: 1. Tuberous Sclerosis Complex
    TSC Facts Countdown for 15 days in May: 1. Tuberous sclerosis complex (TSC) is a genetic disorder with no cure that causes non-cancerous tumors to form in vital organs. 2. Tuberous sclerosis complex (TSC) is estimated to affect 1 in 6,000 live births. Globally, one million individuals have TSC, making it as common as cystic fibrosis or amyotrophic lateral sclerosis (ALS). 3. Approximately ⅔ of individuals diagnosed with tuberous sclerosis complex (TSC) have no family history. The remaining ⅓ of individuals diagnosed with TSC have a parent who also has TSC. 4. If one parent is diagnosed with tuberous sclerosis complex (TSC), the probability of his or her children inheriting the disease is 50%. If parents are unaffected by TSC and have one child with TSC, the probability of having another child with TSC is around 1-2%. 5. Tuberous sclerosis complex (TSC) is the leading genetic cause of both epilepsy and autism spectrum disorders. Seizures occur in approximately 85% of individuals with TSC and intellectual disabilities are found in 45-60%. 6. Approximately 98% of individuals experience one or more skin manifestations (such as angiofibromas) of tuberous sclerosis complex (TSC). 7. Up to 60% of individuals experience kidney involvement with tuberous sclerosis complex (TSC). 8. Tuberous sclerosis complex (TSC) affects men and women in equal numbers and occurs in all races and ethnic groups. 9. Tuberous sclerosis complex (TSC) affects everyone differently; some may have mild symptoms while others are severely impacted. TSC symptoms often vary over a person’s lifetime—someone who has few childhood symptoms may still have severe health problems later in life.
    [Show full text]
  • Psoriasis Findings: Causes, Consequences, and Treatments New Data Reveal More Details Concerning the Extent to Which Psoriasis Affects Individuals
    Take 5 Psoriasis Findings: Causes, Consequences, and Treatments New data reveal more details concerning the extent to which psoriasis affects individuals. Psoriasis Patients Get Less Sleep.In a 16-week study presented at the 2011 AAD Meeting in New Orleans (P 3341), investigators found that psoriasis patients had an average of 12 minutes less of sleep per night than did individuals without psoriasis, which is about an hour and a half less sleep per week. Why psoriasis patients got less sleep is not fully clear, but it is speculated that itching from psoria- sis causes increased sleep disturbances. Authors also indicated that patients with psoriasis were at a 1 60 percent increased likelihood of snoring. In addition, just 47 percent of patients with psoriasis self-reported sleep adequacy, compared to 60 percent of the non-psoriatic population. Alcohol Tied to Development of Psoriasis.Alcohol can directly cause or exacerbate several skin conditions, new research indicates (Skin Therapy Lett. 2011 April; 16(4): 5-7). In particular, alcohol misuse is implicated in the development of psoriasis and discoid eczema, in addition to conferring increased susceptibility to skin and systemic infections. Researchers also noted that alcohol misuse might also 2 exacerbate rosacea, porphyria cutanea tarda, and post-adolescent acne. Patients Can Benefit From Continuous Biologic Treatment. Continuous treatment with ustekinumab (Stelara, Centocor Ortho Biotech) can have a positive impact on a patient’s life, according to new data (2011 AAD, New Orleans. P 3315). The study evaluated patients who either continued or discontinued ustekinumab therapy after 40 weeks of treatment and found a rapid loss of quality of life in patients who discontinued therapy at just 12 weeks after discontinuation.
    [Show full text]
  • Skin Manifestations of Liver Diseases
    medigraphic Artemisaen línea AnnalsA Koulaouzidis of Hepatology et al. 2007; Skin manifestations6(3): July-September: of liver 181-184diseases 181 Editorial Annals of Hepatology Skin manifestations of liver diseases A. Koulaouzidis;1 S. Bhat;2 J. Moschos3 Introduction velop both xanthelasmas and cutaneous xanthomas (5%) (Figure 7).1 Other disease-associated skin manifestations, Both acute and chronic liver disease can manifest on but not as frequent, include the sicca syndrome and viti- the skin. The appearances can range from the very subtle, ligo.2 Melanosis and xerodermia have been reported. such as early finger clubbing, to the more obvious such PBC may also rarely present with a cutaneous vasculitis as jaundice. Identifying these changes early on can lead (Figures 8 and 9).3-5 to prompt diagnosis and management of the underlying condition. In this pictorial review we will describe the Alcohol related liver disease skin manifestations of specific liver conditions illustrat- ed with appropriate figures. Dupuytren’s contracture was described initially by the French surgeon Guillaume Dupuytren in the 1830s. General skin findings in liver disease Although it has other causes, it is considered a strong clinical pointer of alcohol misuse and its related liver Chronic liver disease of any origin can cause typical damage (Figure 10).6 Therapy options other than sur- skin findings. Jaundice, spider nevi, leuconychia and fin- gery include simvastatin, radiation, N-acetyl-L-cys- ger clubbing are well known features (Figures 1 a, b and teine.7,8 Facial lipodystrophy is commonly seen as alco- 2). Palmar erythema, “paper-money” skin (Figure 3), ro- hol replaces most of the caloric intake in advanced al- sacea and rhinophyma are common but often overlooked coholism (Figure 11).
    [Show full text]
  • Tuberous Sclerosis in Early Infancy: a Case Report H
    Brief Report Tuberous Sclerosis in Early Infancy: A Case Report H. John Blossom, MD Fresno, California The diagnosis of tuberous sclerosis in an infant was de­ sclerosis contributed to the delay. A brief review of the layed by 3 months. Failure to take an adequate padent case and the diagnosis of tuberous sclerosis is presented. history because of a language barrier between parents and Key words: Tuberous sclerosis; seizures; infant care. caregivers and to observe the classic stigmata of tuberous / Pam Proa 1993; 36:344-346. The occurrence of seizures in an infant is a frightening evaluation was apparently delayed because of a diagnosis experience for parents and physicians alike. In this case of persistent otitis media, which required repeat admin­ report important historical information and unique phys­ istrations of antibiotics. ical findings arc described that helped determine the During the infant’s 4th month of life, several visits cause of seizures in a 4-month-old infant. to physicians were made for fussiness and fever. Otitis media was diagnosed several times. In addition, the par­ ents observed and reported an abnormality in the baby’s Case Report behavior that they described in Spanish as ataques, a term commonly used to describe fits or seizures. During clin­ The infant weighed 9 lb 3 oz at birth. His mother had an ical encounters interpreters translated conversations be­ uncomplicated prenatal course and an uneventful deliv­ tween the physicians and the parents. Because the ataques ery. The infant’s Apgar scores were 8/8 at 1 and 5 were of very brief duration and no abnormal physical minutes.
    [Show full text]
  • Porphyria Cutanea Tarda* Fátima Mendonça Jorge Vieira 1 José Eduardo Costa Martins 2
    RevABDV81N6.qxd 22.01.07 11:11 Page 573 573 Artigo de Revisão Porfiria cutânea tardia* Porphyria cutanea tarda* Fátima Mendonça Jorge Vieira 1 José Eduardo Costa Martins 2 Resumo: Trata-se de revisão sobre a porfiria cutânea tardia em que são abordados a fisio- patogenia, as características clínicas, as doenças associadas, os fatores desencadeantes, a bioquímica, a histopatologia, a microscopia eletrônica, a microscopia de imunofluorescên- cia e o tratamento da doença. Palavras-chave: Cloroquina; Fatores desencadeantes; Imunofluorescência; Porfiria cutânea tardia; Porfiria cutânea tardia/complicações; Porfiria cutânea tardia/fisiopatologia; Porfiria cutânea tardia/patologia; Porfiria cutânea tardia/terapia Abstract: This is a review article of porphyria cutanea tarda addressing pathophysiology, clinical features, associated conditions, triggering factors, biochemistry, histopathology, electronic microscopy, immunofluorescence microscopy and treatment of the disease. Keywords: Chloroquine; Fluorescent antibody technique; Porphyria cutanea tarda/compli- cations; Porphyria cutanea tarda/pathology; Porphyria cutanea tarda/pathophysiology; Porphyria cutanea tarda/therapy; Precipitating factors INTRODUÇÃO A porfiria cutânea tardia é causada pela defi- A descoberta da atividade diminuída da Urod ciência parcial da atividade enzimática da uroporfiri- na PCT levou a sua subdivisão:8 nogênio-decarboxilase (Urod), herdada ou adquirida, que resulta no acúmulo de uroporfirina (URO) e 7- Porfiria cutânea tardia esporádica (Tipo I, sinto- carboxil porfirinogênio, principalmente no fígado.1 O mática ou adquirida) – Representa percentual que termo porfiria origina-se da palavra grega porphura, varia de 72 a 84% dos casos,9-11 sendo a deficiência que significa cor roxa, e foi escolhido em função da enzimática limitada ao fígado, com atividade da Urod coloração de vermelha a arroxeada da urina de doen- eritrocitária normal.12 Não há história familiar.
    [Show full text]
  • Front Office Staff Flash Card
    Tuberous Sclerosis Complex: An Overview Tuberous Sclerosis Complex (TSC) is a Approximately Multiorgan Genetic Disorder 50,000 people in the United States • It is characterized by the have TSC1 formation of hamartomas, which are noncancerous tumor-like masses2,5 TSC occurs in all races • These tumors can form and ethnic groups, and in in major organs including both genders2 the brain, skin, eyes, and kidneys. Tumors in the heart often occur in children, while lung tumors can The disease occur in adults2,5,6 affects an estimated • Symptoms of TSC can range 1 in 6,000 from mild to severe and can 2 newborns change over time2,6 TSC may not be noticeable. - Because symptoms vary and Diseases with similar may not be immediately recognized US prevalence rates by a health care provider, TSC is include cystic fibrosis often undiagnosed for years (approximately 30,000 people) and amyotrophic Depending on the body organs affected by TSC, lateral sclerosis (ALS), different specialists may be involved, such as a: or Lou Gehrig’s disease (up to approximately Nephrologist 3,4 or for kidney manifestations, such as renal 30,000 people) urologist angiomyolipoma Neurologist for brain manifestations, such as subependymal nodules (SENs) and About 1/3 subependymal giant-cell astrocytomas (SEGAs) of all people with TSC genetically inherit the Dermatologist for skin manifestations disease, while in the remaining individuals, Pulmonologist for lung complications, such as the disease is acquired lymphangioleiomyomatosis (LAM) as a result of spontaneous genetic
    [Show full text]
  • Phlebotomy As an Efficient Long-Term Treatment of Congenital
    Letters to the Editor after chronic gastrointestinal bleeding that resulted in Phlebotomy as an efficient long-term treatment of iron deficiency.4 They treated her with an iron chelator, congenital erythropoietic porphyria resulting in correction of the hemolysis, decreased por- phyrin levels and improved quality of life with reduced Congenital erythropoietic porphyria (CEP, MIM photosensitivity. We recently identified three CEP sib- 263700) is a rare autosomal recessive disease caused by lings with phenotypes ranging from moderate to asymp- impaired activity of uroporphyrinogen III synthase tomatic which were modulated by iron availability, high- (UROS), the fourth enzyme of the heme biosynthetic lighting the importance of iron metabolism in the disease. 1 pathway. Accumulation of porphyrins in red blood cells, Based on these data, we prospectively treated a CEP mainly uroporphyrinogen I (URO I) and copropor- patient with phlebotomies to investigate the feasibility, phyrinogen I (COPRO I), leads to ineffective erythro- safety and efficacy of this treatment. We observed dis- poiesis and chronic hemolysis. Porphyrin deposition in continuation of hemolysis and a marked decrease in plas- the skin is responsible for severe photosensitivity result- ma and urine porphyrins. The patient reported a major ing in bullous lesions and progressive photomutilation. improvement in photosensitivity. Finally, erythroid cul- Treatment options are scarce, relying mainly on support- tures were performed, demonstrating the role of iron in ive measures and, for severe cases, on bone marrow the rate of porphyrin production. transplantation (BMT). Increased activation of the heme The study was conducted in accordance with the biosynthetic pathway by gain-of-function mutations in World Medical Association Declaration of Helsinki ethi- ALAS2, the first and rate-limiting enzyme, results in a 2 cal principles for medical research involving human sub- more severe phenotype.
    [Show full text]
  • ** No Patient Handout Darier Disease In
    ** no patient handout Darier disease in Synopsis Darier disease, also known as keratosis follicularis or Darier-White disease, is an autosomal dominantly inherited disease caused by mutations in the ATP2A2 gene, which encodes a sarco / endoplasmic reticulum calcium-ATPase pump (SERCA2). Although disease penetrance is high, expression is variable, and sporadic mutations may occur. There is no sex predilection. Darier disease presents in early adolescence to mid-adult life, with peak onset in the second decade of life. The disease manifests with greasy, hyperkeratotic papules in a seborrheic distribution, along with palmoplantar pits, acrokeratosis verruciformis-like papules, and characteristic nail findings (candy-cane nails). Leukodermic macules are a rarely reported finding. These small macules occur most frequently on the ventral aspect of limbs and trunk. Their onset is prior to puberty. They have been recognized and reported most frequently in individuals with darker skin phototypes. In additional to cutaneous findings, 15%-50% of patients present with oral involvement, including cobblestoning of the oral mucosa, gingival hypertrophy, and sialadenitis. Esophageal involvement with erosions has been described. The severity of oral disease may parallel that of the cutaneous disease. After onset, the disease is lifelong. It may be accentuated or only prominent in the spring and summer, when exposures to heat, perspiration, and ultraviolet (UV) light are increased. Other exacerbating conditions / factors may include trauma, menstruation, and certain drugs (eg, lithium, oral corticosteroids). The lesions of Darier disease may be pruritic, painful, or malodorous. Along with the appearance, these symptoms may lead to significant psychosocial distress. Patients are at an increased risk of bacterial or viral skin infections.
    [Show full text]
  • Porphyria Cutanea Tarda Presenting As Milia and Blisters
    PRACTICE | CLINICAL IMAGES Porphyria cutanea tarda presenting as milia and blisters Long Hoai Nguyen MD, Karima Khamisa MD n Cite as: CMAJ 2018 May 22;190:E623. doi: 10.1503/cmaj.180152 generally healthy 71-year- old woman was referred to dermatology for evaluation ofA a six-month history of large blis- ters on the dorsal surface of both hands, associated with mild pruri- tus and burning. When we exam- ined the patient’s hands, we observed multiple vesicles and milia, as well as open bullae larger than 5 mm (Figure 1A). Her only medications were iron supplements Figure 1: (A) Milia, vesicles and erupted bullae larger than 5 mm with surrounding area of erythema on the taken orally for “fatigue” over the dorsum of the hand of a 71-year-old woman with new-onset porphyria cutanea tarda. (B) Persistent bilateral past few months. She consumed milia, after therapeutic phlebotomy. two alcoholic beverages per week. A skin biopsy showed a wide band of perivascular immunoreactivity References consistent with porphyria cutanea tarda. Urine porphyrin analysis 1. Handler NS, Handler MZ, Stephany MP, et al. Porphyria cutanea tarda: an was positive for elevated levels of uroporphyrins. intriguing genetic disease and marker. Int J Dermatol 2017;56:e106-17. 2. Ramanujam V-MS, Anderson KE. Porphyria diagnostics — Part 1: a brief overview Porphyria cutanea tarda is an uncommon disease that most of the porphyrias. Curr Protoc Hum Genet 2015;86:17.20.1-26. 1–3 frequently occurs in men older than 40 years. It is caused by a 3. Bissell DM, Anderson KE, Bonkovsky HL.
    [Show full text]