Porphyrias

Question 1

Primary features of acute attacks

Answer 1

abdomen pain
nausea
vomiting
weakness
constipation

other issues: dark urine, seizure

Question 2

Diagnostic testing options for acute hepatic porphyria

Answer 2

random spot urine tests for ALA and PBG

urine porphyrins is non-specific; not diagnostic in isolation

ideal time to test: soon after an acute attack

plasma and fecal porphyrins can be used to confirm diagnosis of AHP type

genetic testing used to confirm AHP type

urine porphobilinogen (PBG)

Question 3

Common misdiagnoses of porphyrias

Answer 3

Appendicitis
Acute pancreatitis
UTI
Ovarian cyst
Cholecystis
GI illness
IBS

Question 4

Inpatient management of porphyrias

Answer 4

Identify and remove known triggers
Send urine porphobilinogen and blood work
Pain meds
Start hemin and IV dextrose

Question 5

Hemin therapy

Answer 5

downregulates stressed hepatic heme biosynthesis

PBG decreases

Question 6

Frequency of Acute neurovisceral attacks

Answer 6

RECURRENT:
- >4/year, can have monthly attacks

SPORADIC:
- < 4/year

Asymptomatic High excretors/chronic high excretors
- clinically asymptomaticbut have high levels of APA and PBG

Question 7

General recommendations for AHP

Answer 7

avoid stressors
maintain well-balanced diet
stay up to date on immunizations to minimize infection risk
Medical alert bracelet

Question 8

Recommendations for asymptomatic high excretors

Answer 8

annual labs and follow ups
monitor kidney and liver function
counseling on potential triggers and means to avoid them

Question 9

Management approaches for AHP

Answer 9

Pain meds, treat symptoms (like nausea and vomiting, neuropathy, seizures)
Hemin
Glucose and Carbohydrate loading to downregulate the biosynthesis pathway
Hormone therapy (good for women when experience acute attack during menstrual cycle)
Liver transplant

Question 10

Challenges of hemin therapy

Answer 10

Need port, IV or PICC line
Risk of thrombophlebitis
Difficult to set up infusion locally
Not available at all hospitals
Long term complications: iron overload and hepatic fibrosis

Question 11

Long term complications of AHP

Answer 11

Kidney disease
Liver disease (increased risk of cancer, Hepatocellular carcinoma)
Neuropathy

Question 12

Givosiran

Answer 12

double-stranded siRNA that causes degradation of ALAS1 mRNA in liver cells through RNA interference –> reduced circulating ALA and PBG
Reductions in chronic pain, improvements in quality of life

Question 13

Erythropoietic porphyria

Answer 13

Most common porphyria in children
Ferrochetalase (last enzyme in heme pathway) deficiency
Accumulation of protoporphyrin in bone marrow reticulocytes, plasma, and liver

Question 14

Erythropoietic porphyria genetics

Answer 14

AR
Mutation in FECH allele AND low-expression variant on other allele
OR FECH mutation on both

Question 15

Erythropoietic porphyria treatment

Answer 15

Beta-carotene
Protective clothing and sunblock
alpha-MSH, increases pigmentation
MT 7117 clinical trials to increase pigmentation

Erythroporetic Protoporphyria: liver transplant

Question 16

X-linked protoporphyria

Answer 16

ALAS2 gene
10% of cases in North America
males more severely affected than females
Higher protoporphyrin levels and risk of liver disease

Question 17

Cutaneous porphyrias clinical manifestations

Answer 17

hand swelling
extreme pain when exposed to sunlight
- tingling, burning, itching
- erythema and edema
- No blistering
- recovery takes several days or several weeks
anemia
iron deficiency
abnormal liver aminotransferases
vitamin D deficiency