Porphyria erythropoietic

In general, the porphyrias described are inherited in an autosomal dominant manner, with the exception of congenital erythropoietic porphyria, which is inherited in a recessive mode. The precise abnormalities in the genes directing synthesis of the enzymes involved in heme biosynthesis have been determined in some instances. Thus, the use of appropriate gene probes has made possible the prenatal diagnosis of some of the porphyrias. 

CEP congenital erythropoietic porphyria, coproporphyrin, EPP erythropoietic protoporphyria, HC hereditary coproporphyria,... 

Fig. 7.3.3a-d Chromatogram of normal urine (a), urine from an individual with acute (in this case intermittent) hepatic porphyria (b), urine from an individual with porphyria cutanea tarda (c), and an undiluted sample from an individual with congenital erythropoietic porphyria (d). See typical pathological values for interpretation... 

Congenital erythropoietic porphyria (CEP) shows a dominance of all I-isomers. Pitfalls... 

Fig. 7.3.6a,b Plasma porphyrins from an individual with porphyria cutanea tarda (a) and from an individual with congenital erythropoietic porphyria (b)... 

Porphyrias are caused by inherited (or occasionally acquired) defects in heme synthesis, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors (see Summary Figure 21.7). With the exception of congenital erythropoietic porphyria, which is a genetically recessive disease, all porphyrias are inherited as autosomal dominant disorders. The mutations that cause the porphyrias are heterogenous (not all are at the same DNA locus), and nearly every affected family has its own mutation. Each porphyria results in the accumulation of a unique pattern of intermediates caused by the deficiency of an enzyme in the heme synthetic pathway. 

Erythropoietic porphyrias The erythropoietic porphyrias (congenital erythropoietic porphyria and erythropoietic proto porphyria) are characterized by skin rashes and blisters lhat appear in early childhood. The diseases are complicated by cholestatic liver cirrhosis and progressive hepatic failure. 

Congenital erythropoietic porphyria - 5 Porphyria cutanea tarda ... 

Uroporphyrinogen III synthase 1 Uroporphyrinogen III Congenital erythropoietic porphyria (AR,10q26) J... 

Primary porphyrias are caused by hereditary enzyme defects in haem synthesis. They can be differentiated clinically into acute and chronic porphyrias as well as pathogenetically into hepatic and erythropoietic porphyrias. Secondary porphyrias are symptomatic porphyrias present in various diseases or caused by poisoning or chemical substances, particularly alcohol. Depending on the preferred manifestation site of the enzyme defect, either in the hepatocytes or erythrocytes (bone marrow), the porphyrias are subdivided into hepatic, erythropoietic and hepatoerythropoietic forms. However, this classification is not always strictly applicable. Based on the course of disease, acute and chronic forms may be differentiated in primary hepatic porphyrias. The acute form is characterized by a congenital reg-... 

Congenital erythropoietic porphyria CEP Uroporphyrinogen tit synthase autosomal recessive... 

The enzymatic metabolic defect is mainly restricted to the erythrocytes or bone marrow. Two distinct clinical pictures can be differentiated congenital erythropoietic porphyria (CEP) and erythropoietic protoporphyria (EPP) (W Kosenow et at, 1953 LA. Magnus et at, 1961). From a hepatological point of view, only EPP is important, (s. tab. 31.12)... 

Tab. 31.12 Constellation of findings in erythropoietic porphyrias (v = variable, N = normal)...

In Table 32-4 the porphyrias are divided into the acute porphyrias, in which acute neurovisceral attacks occur, and the nonacute porphyrias. Other classifications include division into hepatic (acute intermittent porphyria (AIP], hereditary coproporphyria [HOP], variegate porphyria [VP], and PCT) and erythropoietic (congenital erythropoietic porphyria [CEP], erytliropoietic protoporphyria [EPP]) porphyrias according to the main site of overproduction of... 

Figure 32-4 Representative HPLC chromatograms for (a) working standard b, norma) feces c, normal urine d, feces—hereditary coproporphyria e, urine—congenita erythropoietic porphyria f, feces—variegata porphyria g, urine—porphyria cutanea tarda and h, feces—porphyria cutanea tarda chromatographic conditions as described in the appendix on the Evolve site that accompanies this book. Peaks are I, uroporphyrin- 2, uroporphyrin-l 3, heptacarboxyiate porphyrin-l 4, heptacarboxylate porphyrin-tl 5, hexacarboxylate porphyrin 6, pentacarboxylate porphyrin 7, coproporphyrin-1 8, coproporphyrin- ll 9, deuteroporphyrin-IX ...

Aplin C, Whatley SD, Thompson P, Hoy T, Fisher P, Singer C, et al. Late-onset erythropoietic porphyria caused by a chromosome 18q deletion in erythroid cells. J Invest Dermatol 2001 117 1647-9. 

Desnick RJ, Aplin KH. Congenital erythropoietic porphyria advances in pathogenesis and treatment. Br J Haematol 2002 117 779-95. 

Fritsch C, Bolsen K, Ruzicka T, Goerz G. Congenital erythropoietic porphyria. J Am Acad Dermatol 1997 36 594-610. 

Ged C, Morea-Gady I, Taire L et al. Prenatal diagnosis in congenital erythropoietic porphyria by metabolic measurement and DNA mutation analysis. Prenatal Diagnosis 1996 16 83-6. 

Kontos A, Ozog D, Bichakjian C, Lim HW. Congenital erythropoietic porphyria associated with myelodysplasia presenting in a 72-year old man report of a case and review of the literature. Br J Dermatol 2003 148 160-4. 

Verneuil H de, Ged C, Moreau-Gaudry F. Congenital erythropoietic porphyria. In Kadish KM, Smith KM, Guilard R, eds. The porphyrin handbook, vol. 14, Medical aspects of porphyrias. Amsterdam Academic Press, 2003 43-66. 

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