title: Late-onset porphyrias: what are they?
abstract: Porphyrias are inherited disorders of heme biosynthesis. ALA dehydratase porphyria (ADP) and congenital erythropoietic porphyria (CEP) are autosomal recessive porphyrias, and are typically expressed at birth or in childhood. However, a few cases of late-onset recessive porphyrias have been reported. Recently we encountered a late-onset ADP patient who developed symptoms of acute porphyria when he was 63 years old. This was accompanied by polycythemia vera. It was concluded that he developed the porphyria because an abnormal ALAD allele was clonally expanded by polycythemia vera. Upon reviewing the literature, a few cases of late-onset CEP were found to be also associated with hematologic abnormalities suggestive of myelodysplastic syndrome (MDS), another clonal disorder. These findings suggest that these late-onset porphyrias may be heterozygous for their gene defects, but clinical expression may be elicited if there is a loss of heterozygosity, either by a clonal expansion of the porphyric allele or by a loss of function mutation in the other allele.
authors.affiliation: Laboratory of Biochemical Hematology, The Rockefeller University, New York, NY 10021, USA. sassas@yamanouchi.co.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sassa
authors.forename: Reiko
authors.initials: R
authors.lastname: Akagi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nishitani
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Furuyama
mesh_terms: D017668:Age of Onset; D002999:Clone Cells / Q000201:enzymology / Q000473:pathology; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011087:Polycythemia Vera / Q000150:complications / Q000473:pathology; D000623:Porphobilinogen Synthase / Q000172:deficiency / Q000235:genetics; D011164:Porphyrias / Q000201:enzymology / Q000209:etiology* / Q000235:genetics
chemical_list: D000623:Porphobilinogen Synthase