An 11-year-old undernourished girl with a history of seizures presented with recurrent abdominal pain, weight loss, and constipation for 1 year. Examination revealed severe abdominal tenderness and decreased breath sounds on the left side. Investigations showed abnormal urine porphyrin levels. She was diagnosed with acute intermittent porphyria and pulmonary tuberculosis, explaining her recurrent abdominal pain and lung findings.

1. INTERWARD
OF AIP
Dr. Murtaza Kamal
MBBS, MD, DNB
RESIDENT PEDIATRICS
DOP: 22/03/2013
1

2. PATIENT DETAILS
 Name : XXX
 Age/sex: 11 years
/girl
 R/O: XXX
 DOA:05/12/2012
 Informant:Father
2

3. CHIEF COMPLAINTS
 Pain abdomen
 Weight loss
 Non passage of stools
 Poor oral intake
:1 year
:1 year
:10 days
:10 days
3

4. HISTORY OF PRESENTING
COMPLAINTS
 Apparently well one year back
 Pain abdomen
One year
Initially once a week,now increased
With îsing frequency+intensity
Generalized
Sudden in onset
Excruciating in nature
No relation to meals or bowel
No radiation
Relieved with oral analgesics 4

5.  Last ten days:
Intensity increased with poor oral
intake and non passage of
stool(passing flatus)
o Weight loss present since last one year
o No history associated nausea , vomiting or recurrent
diarrhoea,abdominal distention,fatty stools
o No history of fever,cough,jaundice,joint
pain,pallor,rash
5

6. TREATMENT HISTORY
 For the abdominal pain,the child took treatment
from several private practitioners,to be relieved
only symptomatically
 Two months back the child was admitted at a
local hospital for ten days for pain abdomen
which was treated with intravenous drugs and
was discharged
6

7. PAST HISTORY
 The child had ?meningitis at 6 months of age for
which she was treated as an inpatient at a local
hospital for 2 weeks
 At the age of seven years,the child developed
partial seizure for which she was started
carbemazepine.As the seizures could not be
controlled, two more antiepileptics were started
 Presently on Carbamazepine,Lamotrigene and
Clobazam
 No breakthrough seizures since last 3 years
7

8. BIRTH HISTORY
 Antenatal - Uneventful
 First order birth
 Hospital delivery
 FTVD
 B.wt-2.75 kg
 Neonatal period – Uneventful
8

9. IMMUNIZATION HISTORY
RECOMMENDED AGE
OF IMMUNISATION
VACCINE STATUS OF THE
CHILD
6 weeks BCG,DPT-1,OPV-1

10 weeks DPT-2,OPV-2

14 weeks DPT-3,OPV-3

9 months Measles

15 months MMR
X
18 months DPT Booster
X
5 years DT
x
9

10. DEVELOPMENTAL HISTORY
 Had achieved previous milestones appropriately
achieved as per age
 Student of class VI
 Average academic performance
10

11. DIETARY HISTORY
Intake Expected Percentage
Calories 926 kcal/day 1970 kcal/day 47%
Protein 15gm/day 29gm/day 52%
11

12. FAMILY HISTORY
 Non consanguineous marriage
 No chronic illness in the family
 No history of seizures,similar complaints
 No history of contact with Koch’s
11 years 5 years
12

13. SOCIO ECONOMIC HISTORY
 Self owned pucca house with 2 rooms,in
residential area
 Safe water supply-municipality
 Education :Father -Graduate
Mother-Class XII
 Occupation :Father-LIC agent
Mother-Housewife
 Four membered family
 Kuppuswamy classification:Middle class
13

14. EXAMINATION
14

15. Conscious,oriented, sick looking,emaciated
Vitals
 Temperature – 37.50C (axillary)
 PR – 100/min,regular,good in volume and normal in
character, bilaterally synchronous, all peripheral
pulses palpable
 RR – 24/min, abdomino-thoracic
 BP – 102/66 mm Hg Right arm
15

16. ANTHROPOMETRY
Presently
(WHO
standards)
Expected (50th
centile)
Centiles
Weight 20kgs 31.9kgs <3rd centile
Height 135cms 145cms 5th and 15th
centile
BMI 10.97kg/m2 17.2kg/m2 <3rdcentile
16

17. GENERAL PHYSICAL
EXAMINATION
 Hair normal
 BCG scar present
 Pallor present
 No icterus / lymphadenopathy/ pedal
edema/clubbing
 No rash or peri-rectal inflammation
 Skin normal
 No joint swelling
 Spine was normal
17

18. ABDOMEN
18
Scaphoid in shape
Nondistended
Central umblicus
No scars,sinuses or
dilated veins
Soft
Tender epigastrium
Fecolith felt in the left
lower abdomen
No organomegaly
No free fluid
Normal bowel sounds

19. RESPIRATORY SYSTEM
 Trachea-central in position
 Chest-bilaterally symmetrical with no obvious
chest wall abnormality
 Both sides moving on respiration
 No visible dilated veins, scar or sinuses
 Decreased air entry on the left side
 Percussion-resonant
 No added sounds
19

20. CVS
 Normal precordium
 No dilated veins seen
 S1 S2 normal
 No murmur
20

21. CNS
Higher mental functions:
 GCS 15/15,conscious,anxious
 Oriented to time, place, person
 Recent and remote memory normal
 Speech and language normal in fluency
comprehension
 No dysarthria
Cranial nerves:Normal,no focal neurological deficit
21

22. 22
Motor System:
 Generalised muscle
wasting
 Tone normal in all the
four limbs
 Power of muscles 4/5 in
all limbs
 No abnormal movements
 DTR-Normal
 Plantars-B/l flexor
Sensory system:
Normal pain,
temperature ,crude
touch,vibration, joint
position ,pressure ,fine
touch,tactile
localization ,two point
discrimination and
steriognosis
No cerebellar signs
No signs of meningeal
irritation
No abnormal movements

23. SUMMARY
11 years old undernourished girl ,on multiple
antiepileptic for 4 years presented with
complaints of recurrent generalized abdominal
pain with weight loss since past 1year, with
constipation and poor oral acceptance since 10
days
Examination revealed severe pain
abdomen,decreased air entry on left side of
chest,generalised muscle wasting with tender
epigastrium
23

24. PROVISIONAL DIAGNOSIS
Recurrent abdominal pain
with under nutrition
with
Seizure disorder
24

25. DIFFERENTIALS
?Abdominal tuberculosis
? Chronic pancreatitis
?Chronic cholecystitis
25

26. ABDOMINAL TUBERCULOSIS
In favor of Not in favor of
Long history No fever or cough
Weight loss Acute excruciating pain is
uncommon
Prevalence No Contact history
26

27. CHRONIC PANCREATITIS
For Against
Long duration Age
Excruciating nature Postural relief
Tender epigastrium Back radiation
Fatty bulky stools
27

28. CHRONIC CHOLECYSTITIS
For Against
Recurrent nature Uncommon in children
Excruciating pain Vomitting,Dyspepsia
28

29. INVESTIGATIONS
 Hb
 TLC
 DLC
 Platelet count
 PCV
 Serum Na
 Serum K
 Serum Ca
 Serum PO4
 ALP
:9mg/dl
:8200/cu mm
:77/20/01/02
:1,84,000/cu mm
:26.6%
:131meq/L
:4meq/L
:8.9mg/dl
:3.3mg/dl
:255U/L 29

30.  Blood urea
 Serum creatinine
 Serum bilirubin
 SGOT
 SGPT
 Blood culture
 HIV
 CSF analysis
 Urine examination
:49mg/dl
:0.9mg/dl
:0.5mg/dl
:54U/L
:21U/L
:No growth
:Non reactive
:Normal( 0cell/P20,S60)
:2-3pus cells,No growth
30

31. Investigations Patient’s value Normal Values Prev. values
Serum amylase 112U/L 28-100 132.8U/L
Serum lipase 71U/L 0-60 58.5U/L
Serum
triglycerides
167mg/dl 60-165
Serum
cholesterol
237mg/dl 150-250
HDL 45mg/dl 35-55
LDL 158mg/dl upto150
31
Previous investigations:
CECT Abdomen-Normal Study
CECT Head-?Meningoencephalitis ?Non enhancing early granuloma

32.  CXR(12 hours)
 Mtx
 GA for AFB
 Serum carbamazepine
level
:Normal parenchyma and
cardiac shadow,no
hilar lymphadenopathy
:Negative
:Negative(2 times)
:11.40ug/ml(4-12)
32

33. ULTRASONOGRAM-ABDOMEN
Date Finding
05/12/2012
(At admission)
Normal study
08/12/2012 Multiple calculi
in the gall
bladder
33

34. HOSPITAL COURSE
Patient managed conservatively on intravenous
fluids, tramadol ,proton pump inhibitors and
antibiotics,along with continuation of
antiepileptics
Pediatric surgery consultation –MRCP
The relief in pain was only occasional with the
same
34

35. ULTRASONOGRAM-ABDOMEN
Date Finding
13/12/2012 Normal Study
35

36. CT-ABDOMEN
No features of chronic pancreatitis/cholelithiasis:Normal Study
36

37. CT-THORAX
37

38. Consolidation in the left lower zone
38

39. EEG
39

40. Abnormal record suggestive of partial epilepsy with focus at right temporal
region
40

41. CECT-BRAIN
Normal Study
41

42. FURTHER HOSPITAL COURSE
 Gradually the patient started to develop
parasthesias with pain in the upper limbs
 Neurological consultation taken and further
investigations were planned
42

43. FURTHER INVESTIGATIONS
 Serum Lead Level:<1µg/dl (Normal)
 Urine for porphobilinogen-Positive(0-8.8µmol/L)
 Urine for 5-ALA-Positive (0-35µmol/L)
 Urine for total porphyrins-Positive
 NVC-Severe axonal motor and sensory
neuropathy in all four limbs
43

44. FURTHER HOSPITAL COURSE
 The antiepileptics were tapered gradually and
gabapentine was added
 Modified antitubercular drugs (INH,ethambutol
and streptomycin )were started
44

45. FINAL DIAGNOSIS
Acute intermittent porphyria with pulmonary
tuberculosis with partial seizures
45

46. FOLLOW UP
 Pain abdomen has completely subsided and
patient has a good compliance of ATT with
weight gain
46

47. P
O
R
P
H
Y
R
I
A
S 47

48. INTRODUCTION
Porphura(Purple pigment)
Group of metabolic diseases resulting from a partial
deficiency of an enzyme in the heme biosynthetic
pathway
48

49.  The two major cell types that are active in heme
synthesis are hepatocytes and bone marrow
erythroblasts
 85% of total synthesis occurs in erythroid cells
 80% of liver production is used for cytochromes
49

50. HEME BIOSYNTHETIC PATHWAY
50

51. CLASSIFICATION
Acute Non Acute
ALA Dehydratase deficient
Porphyria
Porphyria cutanea tarda
Acute Intermittent porphyria Erythropoitic protoporphyria
Variegate porphyria Congenital Erythropoitic
porphyria
Heriditary Coproporphyria
51

52. Hepatic Erythropoietic
ALA Dehydratase deficient
Porphyria
Erythropoitic protoporphyria
Acute Intermittent porphyria Congenital Erythropoitic
porphyria
Variegate porphyria
Heriditary Coproporphyria
Porphyria cutanea tarda
52

53. Cutaneous Non Cutaneous
Porphyria cutanea tarda ALA Dehydratase deficient
Porphyria
Erythropoitic protoporphyria Acute Intermittent porphyria
Congenital Erythropoitic
porphyria
Variegate porphyria
Heriditary Coproporphyria
53

54. ACUTE PORPHYRIAS
 Acute
 Self-limiting attackschronic+progressive
deficits
 Clinically indistinguishable during acute attacks,
except neurocutaneous porphyrias(dermatologic
changes)
 Acute attacks-increase in PBG + 5-ALAcan be
detected in urine 54

55.  Diagnosis difficult:
Variable clinic course
Lack of understanding about
diagnostic process
Lack of a universal standard for test
result interpretation
55

56. PATHOPHYSIOLOGY OF THE
ACUTE ATTACK
Autonomic Nervous System
Peripheral Nervous System
Hypothalamus
Limbic area
Porphyrins excreted from liver
Accumulates in brain with
neuronal and glial cell damage
ALA crosses the
BBB-causes oxidative
Damage
Symptoms due to porphyrin
precursor accumulation
rather than deficiency of
heme
BBB
idative
effects
ALA induces liver damage
Via oxidative effects
Porphyrins do
Not cross BBB
56

57. MECHANISMS INVOLVED
Excess amounts of PBG or ALA may cause
neurotoxicity
(Meyer et al, 1998)
Increased ALA concentrations in the
brain may inhibit GABA release
 (Mueller & Snyder, 1977; Brennan & Cantrill, 1979)
Heme deficiency may result in
degenerative changes in the central
nervous system
 (Whetsell et al, 1984)
57

58. ACUTE
INTERMITTENT
PORPHYRIA
58

59. AIP
 Most common
 F>M (2:1)
 AD with Incomplete penetrance
 Affected individuals -50% reduction in RBC PBG-
D activity
 Latent prior to puberty
 Incidence highest Northern Europe,Indian data
lacking
 Increased urinary ALA & PBG
59

60. CLINICAL FEATURES
GI Symptoms-MC -95-98%
 Colicky abdominal pain (85–95%)
 Constipation (48–84%)
 Vomiting (43–88%)
 Diarrhea (5–12%)
Peripheral neuropathies(pred. motor) -42–60%
Psychiatric symptoms- 40–58%
Diffuse pain(esp. in upper body)-50–52%
Hypertension-36–54%
Tachycardia-28–80%
Fever-9–37%
Seizures-10–20%
60

61. Most patients completely free of symptoms between
attacks
Attacks involve neuro-visceral symptoms
Sequence of events in attacks
Abdominal painpsychiatric symptomsperipheral
neuropathies
Abdominal pain is severe and lasts for several days
Severe abdomen pain of short (<1 d) duration is
unusual
61

62. PRECIPITANTS OF AN
ACUTE ATTACK
 Drugs that increase demand for hepatic heme
(especially cytochrome P450 enzymes)
 Crash diets (decrease carbohydrate intake)
 Endogenous hormones (progesterone)
 Metabolic stresses (infections, surgery, psychological
stress)
 Cigarette smoking (induces cytochrome P450)
62

63. 63
Commonly Used Drugs
That Precipitate Acute
Attacks in Porphyrias
 Barbiturates
 Chlordiazepoxide
 Chloroquine
 Chlorpropamide
 Rifampicin
 Estrogens
 Ethanol
 Glutethimide
 Griseofulvin
 Imipramine
 Pyrenzenamide
 Methyldopa
 Sulfonamides
Drugs That Are Safe to
Use During Acute
Attacks of Porphyrias
 Acetaminophen
 Aspirin
 Atropine
 Digoxin
 Glucocorticoids
 Insulin
 Narcotic analgesics
 Penicillin
 Phenothiazines
 Streptomycin
S h a h e t a l : A c u t e I n t e r m i t t e n t P o r p h y r i a

64. DIAGNOSIS
 Demonstration of porphyrin precursors(ALA
and/or PBG):essential for diagnosis of acute
porphyrias
 Porphyrin analysis is necessary for the diagnosis
of porphyrias with cutaneous photosensitivity
PBG usually is not included in a urine porphyrin
screen and must be ordered specially
 Molecular diagnostic testing:
 Detection of PBGD mutations in AIP provides
95% sensitivity and around 100% specificity
 Possible to screen asymptomatic gene carrier
64

65.  Urinary ALA and PBG are always
markedly increased in
symptomatic patients with AIP
and even in some asymptomatic
individuals with the inherited
enzyme deficiency
 PBG in urine is oxidized to
porphobilin upon standing, which
gives a dark-brown color to urine,
and often referred to as ‘port-
wine reddish urine’
65

66. APPROACH TO A
CASE OF ACUTE
PORPHYRIA
66

67. 67

68. TREATMENT OF ACUTE ATTACK
 Withdraw all unsafe medications
 Hospitalization to control/treat acute symptoms:
 Seizures – Seizure precautions, medications
 Electrolyte abnormalities
 Dehydration / hyponatremia
 Abdominal Pain – narcotic analgesics
 Nausea/vomiting – phenothiazines
 Tachycardia/hypertension – Beta blockers
 Urinary retention / ileus
68

69.  Monitor respiratory function, muscle
strength, neurological status
 Mild attacks (no paresis or hyponatremia) –
Intravenous 10% glucose at least 300 g per day
 Severe attacks – Intravenous hemin (3-4 mg/kg
qdaily for 4 days) ,can give IV glucose while
waiting for IV hemin
(Normosang-Orphan Europe,U.K.)
69

70.  Haemolytic anaemia in erythropoietic porphyrias
may be treated by blood transfusion
 Cutaneous photosensitivity may be treated by:
 Photoprotection, e.g. with broad-band
sunscreens and/or protective clothing
 Strict avoidance of sunlight exposure
 Change day-night shifts
 B-carotene
70

71. LONG-TERM COMPLICATIONS FROM
SYMPTOMATIC DISEASE
 Hypertension
 Renal failure
 Cirrhosis
 Hepatocellular carcinoma
 Neurological Sequelae
71

72. PREVENTION & FOLLOW-UP: CARING FOR
PATIENTS BETWEEN ATTACKS
 Adequate carbohydrate intake
 Iron overload from hemin
 Hepatocellular carcinoma screening
 End-Stage renal disease prevention
 Avoidance of alcohol, smoking, and exacerbating
drugs
72

73. PROGNOSIS
 Prior to 1970, fatality rates were 50%,now
decreased to 10%
 Since introduction of hemin mortality has
decreased
 Overall mortality in patients with acute attacks
is 3-fold higher than the general population
 Delayed diagnosis and treatment contribute to
higher mortality
73

74. KEY POINTS
 Porphyrias are metabolic diseases resulting from a partial
deficiency of an enzyme in the heme biosynthetic pathway
 Cause acute attacks secondary accumulation of heme
precursors
 Clinical features: abdominal pain, tachycardia,
hypertension, hyponatremia, seizures, motor neuropathy
etc
 Screen for porphyria with qualitative urinary PBG and if
elevated measure quantitative urinary PBG and ALA
 Confirm diagnosis with urinary and fecal fractionated
porphyrins and DNA testing
 Treat acute attacks with IV hemin
 Prevent acute attacks with smoking cessation, avoidance of
inciting agents
74

75. THANKS
75