Metabolic Disease

Prolidase Deficiency ◽

Treatment Mode ◽

Chapter 11 covers Porphyrias (Congenital Erythropoietic Porphyria, Erythropoietic Protoporphyria, Hereditary Coproporphyria, Porphyria Cutanea Tarda, and Variegate Porphyria), Mucopolysaccharidoses (Hunter Syndrome), and Other Metabolic Disorders (Acrodermatitis Enteropathica, Alkaptonuria, Biotinidase Deficiency, Familial Cutaneous Amyloidosis, and Prolidase Deficiency). Each condition is discussed in detail, including dermatologic features, associated anomalies, histopathology, basic defect, treatment, mode of inheritance, prenatal diagnosis, and differential diagnosis.

Metabolic Disease

10.1093/med/9780195397666.003.0011 ◽

2012 ◽

Author(s):

Virginia P. Sybert

Keyword(s):

Metabolic Disease ◽

Metabolic Disorders ◽

Porphyria Cutanea Tarda ◽

Hunter Syndrome ◽

Biotinidase Deficiency ◽

Acrodermatitis Enteropathica ◽

Prolidase Deficiency ◽

Porphyrias – Congenital Erythropoietic Porphyria – Erythropoietic Protoporphyria – Hereditary Coproporphyria – Porphyria Cutanea Tarda – Variegate Porphyria – Mucopolysaccharidoses – Hunter Syndrome – Other Metabolic Disorders – Acrodermatitis Enteropathica – Alkaptonuria – Biotinidase Deficiency – Familial Cutaneous Amyloidosis – Prolidase Deficiency

Amounts of Faecal Porphyrin-Peptide Conjugates in the Porphyrias

Clinical Science ◽

10.1042/cs0430299 ◽

1972 ◽

Vol 43 (2) ◽

pp. 299-302 ◽

Cited By ~ 10

Author(s):

M. R. Moore ◽

G. G. Thompson ◽

A. Goldberg

Keyword(s):

Porphyria Cutanea Tarda ◽

Acute Intermittent Porphyria ◽

Normal Subjects ◽

Peptide Conjugates ◽

Peptide Complex ◽

Variegate Porphyria ◽

Hereditary Coproporphyria ◽

Different Types

1. The levels of ‘X-porphyrin’, a porphyrin-peptide complex, have been studied in the faeces of patients with different types of porphyria, as well as in fifty normal subjects. 2. These levels have been shown to be significantly elevated in untreated porphyria cutanea tarda and in variegate porphyria. 3. Lesser elevations were seen in acute intermittent porphyria and hereditary coproporphyria. There was no elevation in erythropoietic protoporphyria.

The Porphyrias

10.2310/im.1162 ◽

2016 ◽

Author(s):

Karl E Anderson ◽

Attallah Kappas

Keyword(s):

Biosynthetic Pathway ◽

Aminolevulinic Acid ◽

Clinical Symptoms ◽

Porphyria Cutanea Tarda ◽

Acute Intermittent Porphyria ◽

Genetic Traits ◽

Molecular Defects ◽

Clinical Presentations ◽

The porphyrias are uncommon disorders caused by deficiencies in the activities of enzymes of the heme biosynthetic pathway. The enzymatic defects that cause porphyrias are inherited, with the exception of porphyria cutanea tarda, which is primarily acquired. In all porphyrias, there is significant interplay between genetic traits and acquired or environmental factors in the expression of clinical symptoms. This review discusses the classification, pathophysiology, and clinical presentations of the porphyrias. These include those associated with neurovisceral attacks (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and δ-aminolevulinic acid dehydratase [alad] deficiency porphyria) and the porphyrias associated with cutaneous photosensitivity (porphyria cutanea tarda, hepatoerythropoietic porphyria, erythropoietic protoporphyria, and congenital erythropoietic porphyria). Specific emphasis on the epidemiology, molecular defects and pathophysiology, clinical features, diagnosis, and treatment are discussed for each of these disorders. A table lists the safe and unsafe drugs for patients with porphyrias. Figures illustrate the genetic pathways of the disorders and the activities of enzymes of the heme biosynthetic pathway. This review contains 2 highly rendered figures, 1 table, and 96 references.

Plasma Porphyrins in the Porphyrias

Clinical Chemistry ◽

10.1093/clinchem/45.7.1070 ◽

1999 ◽

Vol 45 (7) ◽

pp. 1070-1076 ◽

Cited By ~ 33

Author(s):

J Thomas Hindmarsh ◽

Linda Oliveras ◽

Donald C Greenway

Keyword(s):

Renal Failure ◽

Healthy Subjects ◽

Porphyria Cutanea Tarda ◽

Plasma Concentrations ◽

Acute Intermittent Porphyria ◽

Fluorometric Detection ◽

Clinical Sensitivity ◽

Hereditary Coproporphyria ◽

Coproporphyrin I

Abstract Background: As an aid in the diagnosis and management of porphyria we have developed a method to fractionate and quantify plasma porphyrins and have evaluated its use in various porphyrias. Methods: We used HPLC with fluorometric detection to measure plasma concentrations of uroporphyrin I and III, heptacarboxyl III, hexacarboxyl III, pentacarboxyl III, and coproporphyrin I and III. We studied 245 healthy subjects, 32 patients with classical porphyria cutanea tarda (PCT), 12 patients with PCT of renal failure, 13 patients with renal failure, 8 patients with pseudoporphyria of renal failure, 3 patients with acute intermittent porphyria, 5 patients with variegate porphyria, 5 patients with hereditary coproporphyria, and 4 patients with erythropoietic protoporphyria. Results: Between-run CVs were 5.4–13%. The recoveries of porphyrins added to plasma were 71–114% except for protoporphyrin, which could not be reliably measured with this technique. Plasma porphyrin patterns clearly identified PCT, and its clinical sensitivity equaled that of urine porphyrin fractionation. The patterns also allowed differentiation of PCT of renal failure from pseudoporphyria of renal failure. Conclusions: The assay of plasma porphyrins identifies patients with PCT and appears particularly useful for differentiating PCT of renal failure from pseudoporphyria of renal failure.

An overview of the cutaneous porphyrias

F1000Research ◽

10.12688/f1000research.10101.1 ◽

2017 ◽

Vol 6 ◽

pp. 1906 ◽

Cited By ~ 9

Author(s):

Robert Dawe

Keyword(s):

Liver Disease ◽

Visible Light ◽

Porphyria Cutanea Tarda ◽

Marrow Transplant ◽

Ultraviolet B ◽

Liver Iron ◽

Underlying Liver Disease ◽

Liver Iron Overload ◽

Enzyme Defects

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014.

Benign Hematology

10.1093/med/9780199755691.003.0294 ◽

2012 ◽

Author(s):

David P. Steensma

Keyword(s):

Autosomal Recessive ◽

Autosomal Dominant ◽

Porphyria Cutanea Tarda ◽

Vitamin B12 Deficiency ◽

Hematologic Neoplasm ◽

Disease Penetrance ◽

B12 Deficiency ◽

Metastatic Neoplasm ◽

Bone Marrow Blood

The major forms of benign hematologic conditions are anemia, neutropenia, transfusion reactions, Gaucher disease, and porphyria. Anemia is a sign of disease rather than a disease itself. Anemia results from 1 or more of 3 pathologic mechanisms: inadequate production of red blood cells (RBCs) by the bone marrow, blood loss, or premature destruction of RBCs. The major causes of neutropenia include hematologic neoplasm, metastatic neoplasm involving the marrow, irradiation, vitamin B12 deficiency and folate deficiency, drugs, infections, congenital or acquired primary disorders of hematopoiesis, autoimmune neutropenia, hypersplenism, hemodilution, and benign idiopathic neutropenia. The porphyrias are enzyme disorders that are autosomal dominant with low disease penetrance, except for congenital erythropoietic porphyria, which is autosomal recessive, and porphyria cutanea tarda, which may be acquired and is associated with hepatitis C and hemochromatosis.

Acrodermatitis Enteropathica-Like Eruption in Metabolic Disorders: Acrodermatitis Dysmetabolica Is Proposed as a Better Term

Pediatric Dermatology ◽

10.1111/j.1525-1470.2008.00803.x ◽

2009 ◽

Vol 26 (2) ◽

pp. 150-154 ◽

Cited By ~ 42

Author(s):

Duru Tabanlıoğlu ◽

Sibel Ersoy-Evans ◽

Ayşen Karaduman

Keyword(s):

Metabolic Disorders ◽

Acrodermatitis Enteropathica

(5) Congenital erythropoietic porphyria mimicking hereditary coproporphyria

British Journal of Dermatology ◽

10.1111/j.1365-2133.1991.tb05477.x ◽

1991 ◽

Vol 125 (s38) ◽

pp. 47-47

Author(s):

A. ANSTEY ◽

J. SALISBURY ◽

J. HAWK

Keyword(s):

The porphyrias: advances in diagnosis and treatment

Blood ◽

10.1182/blood-2012-05-423186 ◽

2012 ◽

Vol 120 (23) ◽

pp. 4496-4504 ◽

Cited By ~ 119

Author(s):

Manisha Balwani ◽

Robert J. Desnick

Keyword(s):

Stem Cell ◽

Iron Overload ◽

Porphyria Cutanea Tarda ◽

Molecular Genetic ◽

Diagnosis And Treatment ◽

Decarboxylase Activity ◽

Inborn Errors ◽

Hematopoietic Stem ◽

Aminolevulinate Synthase

Abstract The inborn errors of heme biosynthesis, the porphyrias, are 8 genetically distinct metabolic disorders that can be classified as “acute hepatic,” “hepatic cutaneous,” and “erythropoietic cutaneous” diseases. Recent advances in understanding their pathogenesis and molecular genetic heterogeneity have led to improved diagnosis and treatment. These advances include DNA-based diagnoses for all the porphyrias, new understanding of the pathogenesis of the acute hepatic porphyrias, identification of the iron overload-induced inhibitor of hepatic uroporphyrin decarboxylase activity that causes the most common porphyria, porphyria cutanea tarda, the identification of an X-linked form of erythropoietic protoporphyria due to gain-of-function mutations in erythroid-specific 5-aminolevulinate synthase (ALAS2), and new and experimental treatments for the erythropoietic prophyrias. Knowledge of these advances is relevant for hematologists because they administer the hematin infusions to treat the acute attacks in patients with the acute hepatic porphyrias, perform the chronic phlebotomies to reduce the iron overload and clear the dermatologic lesions in porphyria cutanea tarda, and diagnose and treat the erythropoietic porphyrias, including chronic erythrocyte transfusions, bone marrow or hematopoietic stem cell transplants, and experimental pharmacologic chaperone and stem cell gene therapies for congenital erythropoietic protoporphyria. These developments are reviewed to update hematologists on the latest advances in these diverse disorders.

Isotopic Studies of the Erythropoietic and Hepatic Components of Congenital Porphyria and ‘Erythropoietic’ Protoporphyria

Clinical Science ◽

10.1042/cs0440135 ◽

1973 ◽

Vol 44 (2) ◽

pp. 135-150 ◽

Cited By ~ 24

Author(s):

D. C. Nicholson ◽

M. L. Cowger ◽

J. Kalivas ◽

R. P. H. Thompson ◽

C. H. Gray

Keyword(s):

Bile Pigment ◽

Hepatic Bile ◽

Normal Children ◽

Pigment Formation ◽

Aminolaevulinic Acid ◽

Isotopic Studies ◽

High Utilization

1. Labelled glycine and/or δ-aminolaevulinic acid (ALA) were administered to a child with congenital erythropoietic porphyria (Günther's disease), to three normal children and to three patients with erythropoietic protoporphyria. 2. The utilization of [15N]ALA for the synthesis of faecal ‘urobilin’ in the congenital erythropoietic patient was normal. 3. This suggests there is no significant increase of hepatic bile-pigment formation in congenital erythropoietic porphyria. 4. The utilization of glycine for synthesis of faecal ‘urobilin’ and protoporphyrin in all three patients with erythropoietic protoporphyria was increased. There was a similarly high utilization of [4-14C]ALA administered either orally or intravenously to one of the patients. 5. The utilization of [4-14C]ALA was not affected by phlebotomy. 6. Utilizations of both ALA and glycine for free erythrocyte and plasma protoporphyrins were low. 7. This study provides further evidence that in erythropoietic protoporphyria there is a greatly increased hepatic contribution to the early labelled fraction of bile pigment and that in this disease the excessive protoporphyrin is formed mainly in the liver.