59 Porphyria

Question 1

Inherited or acquired disorders due to altered activities of enzymes in the heme biosynthetic
pathway.

Metabolic intermediates are produced in excess, initially either in the marrow or the liver, and result in neurologic and/or photocutaneous symptoms and signs.

Answer 1

Porphyrias

Question 2

The two organs most active in heme biosynthesis are the:

Answer 2

Marrow and the liver

Types of porphyrias
* Erythropoietic porphyrias
* Hepatic porphyrias

Question 3

The only sex-linked recessive porphyria

Answer 3

X-linked protoporphyria (XLP)

Question 4

The erythropoietic porphyrias

Answer 4

• X-linked protoporphyria (XLP)
• Congenital erythropoietic porphyria (CEP)
• Erythropoietic protoporphyria (EPP) –classic form

CEX- madugo=red

Question 5

Porphyrias with nonblistering photosensitivity

Answer 5

• X-linked protoporphyria (XLP)
• Erythropoietic protoporphyria (EPP) –classic form

Question 6

Principal site of initial accumulation of pathway intermediates in Erythropoietic Porphyrias:

Answer 6

Erythroblasts and reticulocytes

Question 7

Principal site of initial accumulation of pathway intermediates in Hepatic Porphyrias:

Answer 7

Hepatocytes

— Acute hepatic porphyrias
* δ-Aminolevulinic acid dehydratase porphyria (ADP)‡
* Acute intermittent porphyria (AIP)‡
* Hereditary coproporphyria (HCP)‡
* Variegate porphyria (VP)‡

— Porphyria cutanea tarda (PCT)*
— Hepatoerythropoietic porphyria (HEP)*

Question 8

Autosomal recessive disorder is caused by severe (<5% of normal) deficiency of uroporphyrinogen III synthase activity

Reddish brown teeth with red fluorescence under ultraviolet (UV) light

Answer 8

Congenital Erythropoietic Porphyria

Question 9

Characteristic finding of Congenital Erythropoietic Porphyria in utero:

Answer 9

Dark brown porphyrin-rich amniotic fluid

Question 10

the third most common porphyria and the most common in children, is caused by loss-of-function mutations of ferrochelatase (FECH)

Answer 10

Erythropoietic Protoporphyria

Question 11

Caused by gain-of-function mutations of the erythroid form of δ-aminolevulinic acid (ALA) synthase (ALAS [ALAS2])

Answer 11

X-linked Protoporphyria

Question 12

Most common clinical feature of Erythropoietic Protoporphyria

Answer 12

Burning

Question 13

An α-melanocyte–stimulating hormone analogue that increases skin melanin, has shown
benefit in clinical trials and is now approved by the US Food and Drug Administration for Erythropoietic Protoporphyria and X-linked Protoporphyria

Answer 13

Afamelanotide

Question 14

Autosomal recessive disorder is due to a severe deficiency of ALA dehydratase

The rarest form of porphyria

Answer 14

c-Aminolevulinic Acid Dehydratase Porphyria

Question 15

Treatment for c-Aminolevulinic Acid Dehydratase Porphyria and AIP

Answer 15

Hemin

Question 16

Autosomal dominant disorder is caused by partial deficiency of PBG deaminase (also known as hydroxymethylbilane synthase) due to heterozygous mutations of this enzyme

Answer 16

Acute Intermittent Porphyria

Question 17

The most common and often the initial symptom of Acute Intermittent Porphyria

Answer 17

Abdominal pain

Question 18

Attacks of Acute Intermittent Porphyria may be precipitated by:

Answer 18

• Some drugs and hormones (especially progesterone), especially those that induce hepatic ALAS1 and cytochrome P450 enzymes
• Reduced caloric or carbohydrate intake
• Intercurrent illnesses, infection, or surgery

Question 19

Acute attacks of Acute Intermittent Porphyria usually require admission to hospital:

Answer 19

• Mild attacks may be treated by glucose loading (at least 300 g/d intravenously)
• Intravenous hemin (3–4 mg/kg once daily for 4 days or longer) is the treatment of choice for all butmild attacks.

Reconstitution of hemin with human albumin rather than sterile water is recommended to prevent infusion-site phlebitis.

Question 20

Effective in preventing frequent premenstrual attacks in women

Answer 20

Long-acting agonists of gonadotropin-releasing hormone

Question 21

An RNA interference agent that downregulates synthesis of hepatic ALAS1, is approved for
prevention of frequent attacks of acute hepatic porphyrias.

It is given monthly as a subcutaneous injection (2.5 mg/kg body weight).

Answer 21

Givosiran

Question 22

Can be curative in patients who become refractory to other therapies

Answer 22

Liver transplantation

Question 23

Liver imaging at ________ -month intervals is recommended to screen for early hepatocellular carcinoma in all acute porphyrias after age 50.

Answer 23

6- to 12-month

Question 24

Autosomal dominant disorder is caused by partial deficiency of coproporphyrinogen oxidase

Answer 24

Hereditary Coproporphyria

Question 25

Autosomal dominant disorder is caused by partial deficiency of protoporphyrinogen oxidase.

Answer 25

Variegate Porphyria

Question 26

The most common human porphyria

Results from a substantial deficiency of hepatic uroporphyrinogen decarboxylase (UROD) activity, which is due to generation of an inhibitor (uroporphomethene)

An iron-related disorder, with hepatic siderosis in almost all cases.

Answer 26

Porphyria Cutanea Tarda

Question 27

Porphyria Cutanea Tarda

The majority of patients have at least several of the following susceptibility factors:

Answer 27

• Ethanol use
• Smoking
• Estrogen use (in females)
• Hepatitis C
• HFE mutations
• HIV infection
• UROD mutations

Question 28

Porphyria Cutanea Tarda

Most patients do not have UROD mutations and are referred to as

Answer 28

Type 1
(or type 3 if additional family
members have PCT)

Type 2 patients are heterozygous for UROD mutations, sometimes have affected relatives or earlier onset of disease, but are otherwise indistinguishable from type 1.

Question 29

Preferred treatment and is highly effective in

Answer 29

Phlebotomy

Reduce the serum ferritin to approximately 20 ng/mL

A low-dose regimen of hydroxychloroquine (100 mg twice weekly) is also effective when phlebotomies are contraindicated or poorly tolerated.