Exam 2 Flashcards

-acute neurovisceral

-chronic blistering cutaneous photosensitivity

-acute non blistering

gunther's disease

acquired

Dr.Gunther in 1911 in his naming of the congenital erythropoietic porphyria (CEP)

inherited

inherited; acquired

Group of diseases caused by the accumulation of heme substrates caused by primary genetic defects altering any of 8 critical enzymes in the synthesis pathway in combination with environmental or metabolic issues which further reduce affected enzyme activity

composed of four pyrrole rings linked by methene bridges.

metal

porphrinogens

purple

400 nm

550 and 650 nm

fluorescence

False

a metalloporphyrin with iron as the central iron

bone marrow (70%)

liver (15%)

consists of 8 enzymes

four are found in the mitochondria and the other four are found in the cytosol

Metabolized to heme

-abdominal pain, neuropathy, mental disturbances

-AIP,ADP, RCP, VP

-skin manifestation

-CEP,HCP,VP,EPP,HEP,PCT

- 5-Aminolevulinate synthase (ALAS)
- NO - that is why you get plenty of heme, but you get a buildup of other enzymes (since defect is later down the line) and thus, porphoryia

purple, the color urine containing excessive heme substrates changes when exposed to sunlight (UV light)

-unexplained neurovisceral symptoms such as sever abdominal pain or physiatry symptoms

-cutaneous photosensitive on sun-exposed areas, with or without blistering

Neurovisceral disease; most common of acute porphyrias

abdominal pain, visceral; neuro-psychiatric disturbances; peripheral neuropathy including bulbar (difficulty swallowing etc.)

Porphyria cutanea tarda (PCT)

typically results from an ACQUIRED loss of enzymatic function.

to the accumulation of high levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG).

-Measurements of urine porphobilinogen (PBG) in acute attacks

-Must be in a light protected tube if not some anilities could be degraded giving false positive

urine

bile or stool

appears "port wine" due to the conversion of porphobilinogen (PBG) to uroporphyrinogen

-begin with a urine screening that includes precursors to PBG and ALA

-if possible wait to collect urine sample during an acute episode when the patient is experiencing symptoms

24-hour urine collection preserved with sodium carbonate and freeze immediately

protected from light

the water-soluble porphyrins as well as other porphyrins by HPLC using fluorescence detector

X-linked erythropoietic protoporphyria (XLP)

an inherited GAIN of function mutation.

Rare, inherited deficiency of ALA synthase
Most common hereditary sideroblastic anemia

Responds to Vitamin B6 which activates the remaining delta-ALA synthase.

phlebotomy and or chelation therapy to reduce accumulation off iron levels

Microcytic, hypochromic anemia

reduced heme synthesis, which in ineffective increasing erythron iron turnover. causing excess iron in the bone marrow

deficiency in the second heme synthesis pathway.

defective activity of 5-aminovulinic acid dehydratase

autosomal recessive inherited. both parents would has to have the defect

deficiency in the ALA dehydrate activity

abdominal pain and neuropathy symptoms such as disorientation, agitation, hallucination and muscle weakness

IV panhematin (hemin) (feedback inhibition)

acute symptoms (antibodies, seizure medication)

5-aminolvulinic acid (ALA) and slightly marked elevation in (PBG)

enzyme deficiency of enzyme hydroxymethybilane synthase, higher prevalence in scandanavian countries, drugs most commonly precipitate the cause of disease (barbituates, sulfonamides)

Autosomal dominant inheritance and only 1 defective parent is needed

deficiency of the non-erythroid form

abdominal pain that can be very sever

hypertension, restlessness, tremors and excess sweating, overactive sympathetic nervous systems

Panhematin (IV hemin)

GIVLAARI injection

Total serum porphyria

PBG

excess ALA from the liver leads to neuronal toxicity

deficiency of uroporphyrinogen III cosynthase, one of the rarest porphyrias, Gunther's disease, teeth will fluoresce red under ultra violet light, red-brownish discoloration under normal light

mutation in the UROS gene

sever anemia, cutaneous photosensitive, blistering symptoms on sun exposed skin, reoccurring skin damage

uroporphyrin and coproporphyrin

normal PBG

the most common porphyria

typically results from an acquired loss of enzymatic function.

decreased activity of uroporphyrinogen III decarboxylase (UROD, Step 5) in the liver.

(acquired) (80% of the cases)

(inherited) (autosomal dominate) (20% of the cases)

Homogenize inherited family (HEP) (both parent would have to have the defect (very rare)

chronic blistering cutaneous porphyria

-Iron overload (commonly due to hemochromatosis resulting from mutation of the HFE gene)

- Hepatitis C infection

- Alcohol abuse

- Medicinal estrogen use

These porphyrias should be considered whenever a patient presents with the characteristic blistering response to sunlight.

The measurement of total porphyrins in plasma, but total porphyrins are also elevated in the urine.

DNA-based mutation detection, but remember that in PCT only 20% to 30% will have an identifiable mutation.

phlebotomy and chloroquine.

Chloroquine takes longer to work, and may exacerbate hepatotoxicity, but is LESS invasive than regular phlebotomy.

a homozygous mutation of both alleles of the UROD gene and is so called because porphyrins accumulate in both the red cells and liver.

Cutaneous symptoms, photosensitivity, abnormal hair growth, liver disease; appears in childhood, skin damage

Uroporphyriay, heptacarboxyporphyrin, pentacarboxylin

phlebotomy

avoid sun and iron

low dose of chloroquine

neurocutaneous symptoms

it is autosomal dominant and symptoms are similar to AIP. symptoms in female can coincide with the menstural cycle

This enzyme is involved in the production of a molecule called heme. catalyzes the oxygen-dependent oxidation of protoporphyrinogen IX to protoporphyrin IX.

coproporphyrin III in the urine

PCT - porphyria cutanea tarda

HCP - hereditary coproporphyria & VP - variegate porphyria

COPRO III is markedly increased in the urine and feces in symptomatic patients and often persists (especially in feces) when there are no symptoms.

Urinary ALA and PBG levels are increased, though not to the extent that is present in AIP.

You treat the neuro sxs (as you do in AIP) but phlebotomy and chloroquine are not effective treatments for cutaneous lesions

PROTO-oxidase, the seventh enzyme in the heme biosynthetic pathway

- netherland descent living in south africa
- 3 in 1000 whites

- skin photosensitivity
- acute neurovesical crises

blistering skin manifestations are worse than those in PCT and they are more difficult to treat and usually of longer duration

- urine ALA and PBG levels are increased during acute attacks but may return to normal more quickly than in AIP

- increases in fecal protoporphyrin and COPRO III and in urinary COPRO III

- plasma porphryn levels are also increased, particularly when there are cutaneous lesions

- acute attacks are treated as in AIP
- hemin should be started early in most cases
- avoiding sun exposure (few other effective measures for treating skin lesions)

erythroid form of the ALA-synthase (ALA-synthase 2)

ineffective erythropoiesis, weakness , and pallor

refractory hemolytic anemia, pallor, and weakness during infancy

They have secondary hypersplenism, become iron overloaded, and can develop hemosiderosis.

- bone marrow examination reveals hypercellularity with a left shift and megaloblastic erythropoiesis with an abnormal maturation
- sideroblasts

- levels of urinary porphyrin precursors and of both urinary and fecal porphyrins are normal

-activity of erythroid ALA-synthase 2 is decreased in bone marrow, but this enzyme is difficult to measure in the presence of the normal ALA-synthase housekeeping 1 enzyme

- pyridoxine supplementation
- transfusions and chelation therapy if refractory to pyroxidine supplementation

Erythropoietic protoporphyria (EPP) is the most common porphyria to cause....

bone marrow reticulocytes

liver function abnormalities and liver failure requiring transplantation

- substantial increase in protoporphyrin, which is predominantly free and not complexed with zinc, is the hallmark of EPP

- avoid sunlight and wear protective clothing
- cholestyramine and other porphyrin absorbents may be helpful to promote fecal excretion to prevent enterohepatic circulation

c. Porphyria cutanea tarda (PCT)

b. Progesterone

c. Porphyria cutanea tarda (PCT)

FALSE

FALSE

a. IV heme (hemin)

c. Burning pain, erythema, and edema of the skin after sun exposure

Succinyl-CoA + Glycine