Porphyria
ICD-10 E80.0-E80.2
ICD-9 277.1
MedlinePlus 001208
MeSH C17.800.849.617
GENERAL
a group of inherited or acquired disorders of certain enzymes in the heme bio-synthetic pathway
(porphyrin pathway)
clinically induced and histologically identical condition is called pseudoporphyria (iatrogenic porphyria)
"porphyria" term from Greek πορφύρα, porphyra, meaning "purple pigment"
original descriptions are attributed to Hippocrates
first explained biochemically by Dr Felix Hoppe-Seyler in 1874
acute porphyrias were described by the Dutch physician Prof B.J. Stokvis in 1889
TYPES, BROADLY
acute (hepatic) porphyrias
cutaneous (erythropoietic) porphyrias
based on the site of the overproduction and accumulation of the porphyrins (or their precursors)
SYMPTOMS
either neurological complications or skin problems (or occasionally both)
normal serum and urine porphyrin levels
purple discolouration of feces and urine in patients during an attack
ACUTE PORPHYRIA
hepatic
primarily affect the nervous system
frequently misdiagnosed
SYMPTOMS
abd pain, vomiting
acute neuropathy
muscle weakness
siezures
mental disturbances; hallucinations, depression, anxiety, and paranoia
cardiac arrhythmias and tachycardia may develop
autonomic nervous system is affected
pain can be severe and can, in some cases, be both acute and chronic in nature
constipation common, diarrhea possible
acute porphyria pts (AIP, HCP, VP)
DIFFERENTIAL
polyneuropathy DDX: Guillain-Barré syndrome
Systemic lupus erythematosus: photosensitivity, pain attacks, other sx in common
ETIOLOGY
Not all porphyrias are genetic
patients with liver disease who develop porphyria as a result of liver dysfunction, mb jaundiced
SEQUELLAE
incr lifetime risk of hepatocellular carcinoma
CUTANEOUS PORPHYRIA
erythropoietic in etio
photosensitivity (photodermatitis)
blisters
necrosis of the skin and gums
itching
swelling
increased hair growth on areas such as the forehead
mb no abdominal pain, distinguishing it from other porphyrias
accumulated heme precursors excreted in the urine may cause various changes in color
after exposure to sunlight
to a dark reddish or dark brown color, or rarely purple or red
DIAGNOSIS
diagnosed through spectroscopy and biochemical analysis of blood, urine, and stool
urine estimation of porphobilinogen (PBG) is the first step if acute porphyria is suspected
(decr heme-->compensatory incr production of precursors incl PBG)
in nearly all cases of acute porphyria syndromes, urinary PBG is markedly elevated
EXCEPTION: very rare ALA dehydratase deficiency, or hereditary tyrosinemia type I(?)
in cases of mercury- or arsenic poisoning-induced porphyria other changes in porphyrin profiles appear
--elevations of uroporphyrins I & III, coproporphyrins I & III and pre-coproporphyrin
repeat testing during an attack and subsequent attacks mb required for detection
levels return to normal (or close) between attacks
"The urine screening test has been known to fail in the initial stages of a severe life threatening attack of acute intermittent porphyria.[citation needed]"
"up to 90% of genetic carriers of the mc, dominantly inherited acute hepatic porphyrias (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria) have been noted in DNA tests to be latent for classic symptoms and may require DNA or enzyme testing"???
The exception to this may be latent post-puberty genetic carriers of hereditary coproporphyria.
most porphyrias are rare conditions
general hospital labs typically won't be able to assess it
best to take sample during acute attack
proper handling of sample: protect from light and either refrigerate or preserve (how?)
porphyrin studies are negative, one has to consider pseudoporphyria. A careful medication review often will find the inciting cause of pseudoporphyria.
[edit]Additional tests
Further diagnostic tests of affected organs may be required, such as nerve conduction studies for neuropathy or an ultrasound of the liver. Basic biochemical tests may assist in identifying liver disease, hepatocellular carcinoma, and other organ problems.
[edit]Pathogenesis
In humans, porphyrins are the main precursors of heme, an essential constituent of hemoglobin, myoglobin, catalase, peroxidase, respiratory and P450 liver cytochromes.
Heme synthesis-note that some reactions occur in the cytoplasm and some in the mitochondrion (yellow)
Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. Heme function plays a central role in cellular metabolism. This is not the main problem in the porphyrias; most heme synthesis enzymes-even dysfunctional enzymes-have enough residual activity to assist in heme biosynthesis. The principal problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine the location of accumulation, whether they induce photosensitivity, and whether the intermediate is excreted (in the urine or feces).
There are eight enzymes in the heme biosynthetic pathway, four of which-the first one and the last three-are in the mitochondria, while the other four are in the cytosol. Defects in any of these can lead to some form of porphyria.
The hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain and an acute polyneuropathy), while the erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth.
Variegate porphyria (also porphyria variegata or mixed porphyria), which results from a partial deficiency in PROTO oxidase, manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks. All other porphyrias are either skin- or nerve-predominant.
SOURCE
http://en.wikipedia.org/wiki/Porphyria