Metabolic disorders

Question 1

Porphyrias

Deffinition

Answer 1

a set of metabolic disorders
caused by disturbances in the synthesis of heme,
mostly – hereditary enzyme defect

Question 2

Clinic of Porphyria

Answer 2

• acute and nonacute forms
• disease patterns differ depending on the affected enzyme
  1. Photosensitive skin eruptions
  2. Systemic symptoms: abdominal pain, neuropathy

Question 3

Porphyria

Treatment

Answer 3

=> Prevention of flares – avoidance of triggers  
=> Symptomatic treatment in flares: 
1. Phlebotomy  
2. Pain management – NSAIDs, opioids 
3. Antiemetics 
4. Antiepileptics  
5. Tachycardia – betablockers  
=> Acute attack 
1. Hemin IV – decreases heme biosynthesis  -

Question 4

Porphyrias

Pathophysiology

Answer 4

Heme is produced in the liver and bone marrow

8 steps starting w/ glycine

Enzyme absence/ dysfunction = buildup of precursors => accumulate in tissues => clinical symptoms

Question 5

Porphyrias may be acquired by:

Answer 5

Alcohol abuse

Infections (hepatitis C, HIV/AIDS)

Increased estrogen levels

Question 6

Porphyria

Clinical presentation

Answer 6

Chronic porphyria: skin manifestations like blisters and erosions

Acute porphyria: systemic findings like abdominal pain, liver enzymes elevation

Question 7

Most common forms of Porphyria

Answer 7

1. PCT
2. Acute intermittent porphyria AR
3. Erythropoietic porotoporphyria AD

Question 8

Porphyria cutanea tarda

enzyme, AD/AR/acquired

Answer 8

Defect in eroporphyrinogen III decarboxylase => buildup of eroporphyrinogen III => elevated liver functions enzymes

Inherited AD/ acquired

Question 9

Porphyria cutanea tarda

Sy

Answer 9

1. Skin photosensitivity
   - Blisters
   - Scars (face, back of hands)
2. Hypertrichosis
3. Hyperpigmentation
4. Dark-colored urine
5. Liver damage:
   - Elevated liver functions enzymes
   - Liver nodules on ultrasound

Question 10

Acute intermittent porphyria

Answer 10

Peak incidence in 3rd decade of life

Defect in porphobilinogen deaminase => buildup of porphobilinogen (PBG) and D-Aminolevulinic acid (ALA)

Question 11

Acute intermittent porphyria

Sy

Answer 11

Colicky abdominal pain

Neurologic abnormalities

Disorientation

Question 12

Congenital erythropoietic porphyria

Answer 12

Defect in uroporphyrinogen III synthase

Question 13

Congenital erythropoietic porphyria

Sy

Answer 13

Skin photosensitivity (blisters)

Erythrodontia

Colicky abdominal pain

Question 14

Porphyria

Diagnosis

Answer 14

1. Elevated PBG or other porphyrins in
   - Urine
   - Blood
   - Stool
2. Discolored urine when left standing (yellow – dark red)
3. Confirmation test
   - Test of suspected enzyme defect

Question 15

Porphyria

DD.

Answer 15

1. Lead poisoning
2. Acute anemia
3. Hepatitis B and C
   4, Hodgkin lymphoma
4. Acute lymphoblastic leukemia (ALL)