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AIP PORPHYRIA - DIAGNOSIS & TREATMENT
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Clinical Findings
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PORPHYRIA FACTS:

AIP DIAGNOSIS & TREATMENT

DIAGNOSIS
Diagnosis of AIP is made on clinical grounds and increased erythrocytic and

urinary porphobilinogen and aminolevolinic acid (ALA) levels (metabolic

intermediates of heme).



SOURCE:

The Porphyrias

Anderson, Karl E

Cecil Textbook of Medicine,

13th ed. Mc Graw Hill,

1994.

+++++++++++



Acute intermittent porphyria can be diagnosed by increases in urine

delta-aminolevulinic acid and porphobilinogen and confirmed by reduced

erythrocyte porphobilinogen deaminase activity and normal or near-normal stool

porphyrins.



SOURCE:

Clinical Biochemistry

1999 Nov;32(8):609-19

++++++++++++



About 14% of AIP patients will have a normal PBG-Deaminase level during red

blood cell testing.



SOURCE:

Robert Johnson MD

Internal Medicine

++++++++++++



Fourteen percent of AIP patients will appear normal in PBG-D levels in blood

testing.



SOURCE:

Clinical Biochemistry

1999 Nov;32(8):609-19

++++++++++++



AIP mimics a variety of other disorders and is quite difficult to diagnose on the

basis of signs and symptoms alone.



SOURCE:



Acute intermittent porphyria in a

children's psychiatric hospital.

Boon, F. F. and C. Ellis

J Am Acad Child Adolesc Psychiatry

1989; 28(4): 606-9.

+++++++++++



Diagnosis of AIP is made on clinical grounds and increased erythrocytic and

urinary porphobilinogen and aminolevolinic acid (ALA) levels (metabolic

intermediates of heme).



SOURCE:

The Porphyrias

Anderson, Karl E

Cecil Textbook of Medicine,

13th ed. Mc Graw Hill,

1994.

+++++++++++



AIP Type I can be confirmed by specific porphobilinogen deaminase in the

blood.



SOURCE:

Diagnostic dilemmas in acute intermittent porphyria.

Periasamy V, al Shubaili A, Girsh Y.

Department of Neurology

Ibn Sina Hospital

Safat, Kuwait.

Medical Principles & Practice

2002 Apr-Jun;11(2):108-11

+++++++++++



A patient can be initially diagnosed erroneously with a negative screening test

for AIP and consequently treated inappropriately.



SOURCE:

Diagnostic dilemmas in acute intermittent porphyria. A case report.

Periasamy V, al Shubaili A, Girsh Y.

Department of Neurology

Ibn Sina Hospital

Safat, Kuwait.

Medical Principles & Practice

2002 Apr-Jun;11(2):108-11

++++++++++





Diagnosis of AIP Type I is made on clinical grounds and increased erythrocytic

and urinary porphobilinogen and aminolevolinic acid (ALA) levels (metabolic

intermediates of heme).



SOURCE:

The Porphyrias

Anderson, Karl E

Cecil Textbook of Medicine,

13th ed. Mc Graw Hill,

1994.

+++++++++++



Diagnosis is made on clinical grounds and increased erythrocytic and urinary

porphobilinogen and aminolevolinic acid (ALA) levels (metabolic intermediates

of heme).



SOURCE:

Metabolic Disorders

Porphyrias: Clinical Manifestations, Diagnosis and Treatment

Bernardo Haddock Lobo Goulart & Samanta Teixeira Basto

+++++++++++









AIP mimics a variety of other disorders and is quite difficult to diagnose on the

basis of signs and symptoms alone.



SOURCE:

Dr. Robert Johnson M.D.

Retired Clinician

++++++++++



AIP is manifested with a wide spectrum of clinical manifestations and it is called

"the great imitator"."



SOURCE:

Vojnosanit Pregl

2001 Jan-Feb;58(1):95-9

Acute intermittent porphyria as a problem in

differential diagnosis

Preradovic M, et. al.

++++++++++++



Acute intermittent porphyria is the most common type of acute porphyria.



SOURCE:

"The Porphyrias"

Karl E. Anderson M.D.

HEPATOLOGY:

A Textbook of Liver Disease

W.B. Saunders Company

Philadephia 1996

++++++++++



PBG excretion may remain high during remission in AlP and can even be

increased substantially in affected adults who have never had an acute attack.



In these individuals, PEG increases still further during an acute attack but, in

practice, this change is often difficult to detect and attribution of symptoms to

acute porphyria in such circumstances requires careful clinical assessment.



However, a normal PEG concentration excludes porphyria as the cause of

symptoms in an individual with AIP.



SOURCE:

Front line tests for the investigation of suspected porphyria.

A C Deacon, G H Elder.

Journal of Clinical Pathology.

July 2001

v54 i7 p500.

++++++++++++

Proper diagnosis of AIP can be made after repeating the screening test followed

by specific tests of porphobilinogen deaminase.



SOURCE:

Diagnostic dilemmas in acute intermittent porphyria. A case report. Periasamy V,

al Shubaili A, Girsh Y.

Department of Neurology

Ibn Sina Hospital

Safat, Kuwait.

Medical Principles & Practice

2002 Apr-Jun;11(2):108-11

++++++++++++



Many AIP gene carriers are assymtomatic.



In the absence of factors that precipitate an attack, many, if not most, individuals

may go undiagnosed.



Morover, the signs and symptoms of AIP when present, may be ascribed to

more common causesof abdominal pain or neurological dysfunction.





SOURCE:

Acute Intermittent Porphyria

Scheiber, William E. et. al.

American Jornal of Clinical Pathology

Vol. 103 No. 6

June 1995

+++++++++



Early diagnosis is important in patients with of acute intermittent porphyria (AIP)

in patients with atypical presentation.



SOURCE:

Diagnostic dilemmas in AIP

Periasamy V, et. al.

Department of Neurology,

Ibn Sina Hospital,

Safat, Kuwait.

Medicine Principles & Practices

2002 Apr-Jun;11(2):108-11

+++++++++



AIP patients can be initially diagnosed erroneously with a negative screening

test for AIP and consequently treated inappropriately.



SOURCE:

Diagnostic dilemmas in AIP

Periasamy V, et. al.

Department of Neurology,

Ibn Sina Hospital,

Safat, Kuwait.

Medicine Principles & Practices

2002 Apr-Jun;11(2):108-11

+++++++++++++



AIP - CLINICAL FINDINGS





The clinical pattern of AIP involves abdominal, neurologic and psychiatric

symptomatology.



SOURCE:

Acute intermittent porphyria

Sedlak T, et. al.

Bratislava Lek Listy, Slovakia

++++++++++++



AIP is marked constipation, nausea, vomiting, postural hypotension, and

hypertension as common features.



SOURCE:

British Medical Journal

Helen Thadani

Diagnosis and management of porphyria

Bristish Medical Journal

June 17, 2000

++++++++++++



In the 1966 "The Porphyrias" published in Scientific American journal the

following clinical and diagnostic features of AIP were published.





Acute females account for 63% of AIP patients.



General symptoms of AIP



90% experience abdominal pain.



87% experience abdominal tenderness



72 % experience red or dark urine



66% experience nonabdominal pain



61 % experience nausea & vomiting



56 % experience constipation



28% experience loss of appetite



23 % experience amenorrhea (absence of menses)



11 % experience breast secretions



9 % experience diarrhea





Neurologic symptoms of AIP



74% experience peripheral neuropathy



27% experience sensory disorder



16% experience respiratory paralysis



56 % experience behavorial change



40% experience irritability



40% experience anxiety



30 % experience hallucinations



30 % experience confusion



12 % experience seisure



28 % experience depressed or absent tendon reflexes



28% experience cranial nerve involvement





Physical findings of AIP





83 % experience red or dark urine



50 % experience tachycardia



44 % experience labile hypertension



31 % experience fever



24 % experience postural hypotension



12 % experience profused sweating



11 % experience hypertrichosis (hirsutism - excessive body hair)



8 % experience hyperpigmentation



46% experience muscle denevation



27 % experience dexreased nerve conduction velocity



SOURCE:

Scientific America

The Porphyrias

+++++++++











Abdominal examination in AIP usually finds nothing remarkable.



Despite the intense pain, the findings on abdominal examination often are

nonspecific."



SOURCE:

Medicine Journal

February 22 2002

Volume 3, Number 2

"Acute intermittent porphyria"

Thomas G DeLoughery, MD

Associate Director

Department of TransfusionMedicine

Division of Clinical Pathology

Associate Professor

Department of Medicine

Division of Hematology and Medical Oncology

Oregon Health Sciences University

Portland, Oregon

++++++++++++



Catecholamine levels can increase up to 10-fold during an exacerbation of AIP.



SOURCE:

Hypertension and renal disease in acute intermittent porphyria

Andersson C, Lithner F.

Journal of Internal Medicine

1994;236:169-175.

+++++++++++++++

Not uncommonly, there may be fever and leukocytosis associated.



SOURCE:

Dr. Robert Johnson M.D.

Retired Clinician



+++++++++++++



Folate damage was found in conjunction with Acute Intermittent Porphyria in a

12 year old boy.



The AIP was confirmed and heretofore been considered rare before puberty.



SOURCE:

.Neurology 43(7):

1438-9.

1993

Folate deficiency and acute intermittent

porphyria in a 12-year-old boy."

DiMario, F. J., Jr., J. J. Quinn, et al.

+++++++++++







AIP Clinical pattern involves abdominal, neurologic and psychiatric

symptomatology.



SOURCE:

Acute intermittent porphyria

Sedlak T, Pontuch P, Duris I.

Univerzity of Komenskehov

Bratislava, Slovakia

Bratislava Lek Listy

1998 Oct;99(10):536-7

+++++++++++



Erythrocyte PBGD activity is decreased in only 84% of AIP patients.



AIP patients with results within the reference interval. are mainly in the variant

form of AIP.



SOURCE:

Molecular and biochemical studies of acute

intermittent porphyria

Kauppinen R, et. al.

Department of Medicine,

Division of Endocrinology,

University Hospital of Helsinki,Finland.

Clinical Chemistry

2002 Nov;48(11):1891-900

+++++++++++++



Acute intermittent porphyria mimics a variety of commonly occurring disorders

and thus poses a diagnostic quagmire.



SOURCE:

Journal of Psychotherapy

1995;

64(3-4):121-30

"Porphyria: reexamination of psychiatric implications."

Burgovne K. MD et al.

Harbor-UCLA Medical Center,

Torrance 90509, USA.

+++++++++++++



Abdominal pain is usually the first sign of AIP,



SOURCE:

The Porphyrias

Meyer, Urs A.

Harrison's Principles of Internal Medicine,

12th ed. Mc GrawHill, 1991.

+++++++++++



CRIM -Positive AIP (Type III) is characyterized by decreased PBG deaminase

activity.



SOURCE:

The Porphyrias

Kappas, A. et. al.

The Metabolic Basis of Inherited Disease

7th Edition 1995

++++++++++++



CRIM Negative AIP (Type I) is a subtype of AIP.



SOURCE:



The Porphyrias

Kappas, A. et. al.

The Metabolic Basis of Inherited Disease

7th Edition 1995

++++++++++++

In a diagnosis of Acute Intermittent Porphyria (AIP) there is a deficiency of PBG

deaminase (50% of normal) activity in erythrocytes except for 14% which belong

to a subtype.

SOURCE:

The Porphyrias

Medical Handbook

1997

+++++++++

Laboratory findings in AIP show that the defect in porphobilinogen deaminase

causes a build up of ALA and porphobilinogen (PBG) which causes their

increased secretion in the urine.



SOURCE:

Acute Intermittent Porhyria

Anne LeMaistre, M.D.

1995

TMC

++++++++



Manifestations of AIP vary and may lead to very different clinical pictures.



SOURCE:

Symptoms due to porphyria

Schattenberg AV et. al.

Ned Tijdschur Geneeskd

August 8; 142 1998

++++++++



AIP Type II is without erythrocyte PBG Deaminase deficiency.



APproximately 14% of all AIP patients carry this subtype.



SOURCE:

The Porphyrias

Kappas, A. et. al.

The Metabolic Basis of Inherited Disease

7th Edition 1995

+++++++++++



The activity of PBG deaminase is half normal, both in acute and latent cases in

all but 14% of AIP patients, those with a subtype. (AIP Type II.)



SOURCE:



The Porphyrias

Alana Adams RPH

Welsh Drug Information Center

Cardiff, Wales, U.K.

++++++++++++++





Acute intermittent porphyria urine studies will often show variants do to drugs

such as barbiturates, sulfonamides, and griseofulvin which also may precipitate

acute episodes.



SOURCE:

Anderson KE, Bloomer JR,

Bolwell B, Lichtin AE.

Department of Dermatology,

Columbia University College of

Physicians and Surgeons, New

York, New York, USA

+++++++++++



AIP should be considered in individuals with unexplained recurrent weakness

and limb pain.



Once diagnosis is established, effective therpy can often be prescribed,

andexacerbating medications can be avoided."



SOURCE:

Arthritis and Rheumatism

March 1997 Vol. 40 No. 3

page 587

+++++++++++++



Because AIP is considered to be somewhat rare and can mimic a host of other

more common conditions, its presence is often not suspected.



SOURCE:

Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

+++++++++++++



Often AIP is not diagnosed or is diagnosed incorrectly because AIP can mimic

many other more common diseases.



SOURCE:

Robert Johnson MD

Internal Medicine

+++++++++++++

The diagnosis of AIP and other types of porphyria is sometimes made incorrectly

in patients who do not have porphyria at all, particularly if laboratory tests are

improperly done or misinterpreted.



SOURCE:

Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

+++++++++++++



In general for a diagnosis of AIP one must have increased evels of

ALA and PBG in 24 hour urine tests.



For Type I AIP patients there will also be a diminished level of PBG-deamanase

in the red blood cells.



SOURCE:

Robert Johnson MD

Internal Medicine

+++++++++++++







The finding of increased levels of delta-aminolevulinic acid (ALA) and

porphobilinogen (PBG) in urine establishes that one of the acute porphyrias is

present.



If PBGD is deficient in normal red blood cells then the diagnosis of AIP is

established.



SOURCE:

Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

+++++++++++++



Measuring PBGD in red blood cells should not be relied upon by itself to

exclude AIP in a sick patient, because the enzyme is not deficient in red blood

cells of all AIP patients.



SOURCE:

Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

+++++++++++++





AIP Laboratory diagnosis is based on the detection of delta-aminolevulinic acid,

porphobilinogen, uroporphyrin and coproporphyrin in the urine.



SOURCE:

Acute intermittent porphyria

Sedlak T, Pontuch P, Duris I.

Univerzity of Komenskehov

Bratislava, Slovakia

Bratislava Lek Listy

1998 Oct;99(10):536-7

++++++++++++++



To the degree that folic acid is able to activate and stimulate PBGD activity it

matters little if the mutation is a Type I or a Type II mutation diminished

levels of PBGD in every mitochondrial bearing cell excluding the blood in

Type II activity of PBGD.



SOURCE:

Robert Johnson MD

Internal Medicine

Retired Clinican

PES Advisory Board

++++++++++++







In Type II AIP the genetic defect does not cause a PBGD deficiency that is

measurablein the blood and that this does occur in approximately 14% of the

population.



This can and has led to problems in getting a diagnosis but has little or no effect

on treatment.



SOURCE:

Robert Johnson MD

Internal Medicine

+++++++++++++



The genetic mutation that results in Type II AIP,while not affecting PBGD levels

in the blood, DOES result in diminished PBGD levels in EVERY other

mitochondria bearing cell of the body.



SOURCE:

Robert Johnson MD

Internal Medicine

+++++++++++++



DNA testing and liver biopsy as well as the standard 24 hour urine tests can

prove diagnosis of AIP.



SOURCE:

Robert Johnson MD

Internal Medicine

Retired Clinican

PES Advisory Board

++++++++++++++++



In acute intermittent porphyria, (AIP) porphobilinogen and delta aminolevulinic

acid are elevated in acute attacks.



SOURCE:

Mercedes Ramirez FNP

Hemotology

+++++++++++



Out of 385 AIP patients 87% had lowered, 8% had overlapping and 5% had

normal PBGD activity.



Gene carriers of AIP having slight, moderate or high metabolic aberrations of

excretion parameters are recognized by analysis of urinary heme precursors and

faecal porphyrins.



The haem precursor excretion of the groups with lowered, overlapping and

normal PBGD activity in erythrocytes compared to each other is not significantly

different but differs significantly (p < 0.001) from the normal values.



One individual suffering from AIP was detected in a family with normal PBGD.



SOURCE:

Heme precursors and porphobilinogen deaminase in erythrocytes and

lymphocytes of patients with acute intermittent porphyria.

Gross U, Jacob K, Frank M, Doss MO.

Abteilung fur Klinische Biochemie

Philipps-Universitat

Marburg, Germany.

Cell Mol Biol (Noisy-le-grand).

1997 Feb;43(1):29-35.

++++++++++

A deficiency of PBG deaminase (50% of normal) activity in erythrocytes is found

is AIP Type I patients.



In AIP Type II the PBG deaminase will be normal.



SOURCE:

The Porphyrias

Clinical Laboratory Studies

Biochemistry Department

School of Medicine

+++++++++



In AIP they may be mild increases of urinary uroporphyrin and coproporphyrin

found.



SOURCE:

Mercedes Ramirez FNP

Hemotology

+++++++++++



AIP clinical features of an acute attack vary greatly.



SOURCE:

British Medical Journal

Helen Thadani

Diagnosis and management of porphyria

Bristish Medical Journal

June 17, 2000

+++++++++



Porphobilinogen is increased in many but not all patients with acute intermittent

porphyria in latent periods.



SOURCE:

Mercedes Ramirez FNP

Hemotology

+++++++++++



The activity of PBG deaminase is half normal, both in acute and

latent cases in all but 14% of AIP patients, those with a subtype.



SOURCE:

The Porphyrias

Alana Adams RPH

Welsh Drug Information Center

Cardiff, Wales, U.K.

+++++++++





Quantitative porphobilinogen is a better test than delta aminolevulinic acid

overall for acute intermittent porphyria, but bothare used as well as the

Watson-Schwartz test.



SOURCE:

Mercedes Ramirez FNP

Hemotology

+++++++++++



Lymphocytes can be stored in liquid nitrogen for 3 months without loss of PBGD

activity.



Specific PBGD activity in lymphocytes is 5% from specific PBGD activity in

erythrocytes.



In AIP patients with lowered specific PBGD activity in erythrocytes specific

PBGD activity is lowered to the same extent in their lymphocytes.



SOURCE:

Heme precursors and porphobilinogen deaminase in erythrocytes and

lymphocytes of patients with acute intermittent porphyria.

Gross U, Jacob K, Frank M, Doss MO.

Abteilung fur Klinische Biochemie

Philipps-Universitat

Marburg, Germany.

Cell Mol Biol (Noisy-le-grand).

1997 Feb;43(1):29-35.

+++++++++++



In AIP patients which can be divided into three different groups, the first group

has lowered, the second overlapping and the third normal porphobilinogen

deaminase activity.



SOURCE:

Heterogeneity of acute intermittent porphyria: a subtype with normal erythrocyte

porphobilinogen deaminase activity in Germany.

Gross U, Honcamp M, Doss MO.

Abteilung fur Klinische Biochemie

Klinikum der Philipps-Universitat Marburg

Deutschland.

European Journal of Clinical Chemistry & Clinical Biochemistry. 1996

Aug;34(8):613-8.

+++++++++++







The acute visceral pain of porphyria has been confused with virtually every

acute surgical condition of the abdomen and has resulted in exploratory

laparotomies.



Laparotomies are incisions that go through the flank, or more generally, through

any part of the abdominal wall on occasion.



SOURCE:



Dr. Robert Johnson M.D.

Retired Clinician

+++++++++++



The clinical manifestations of AIP include paroxysms of acute abdominal pain,

neurologic changes and paresis.



SOURCE:

Prognosis of acute porphyria

Kauppinen R, Mustajoki P.

Medicine. 1992;71:1-13

++++++++++



Catecholamine levels can increase up to 10-fold during an exacerbation of AIP.



SOURCE:

Hypertension and renal disease in acute intermittent porphyria

Andersson C, Lithner F.

Journal of Internal Medicine

1994;236:169-175.

++++++++++++



An investigation of AIP subjects did not demonstrate an increased rate of

bilirubin

production.



This provides evidence that ineffective erythropoiesis does not occur in these

patients.



SOURCE:

Neurology

July 1993

F.J. DiMArio Jr., M.D., et. al.

+++++++++++





Signs and symptoms of AIP rarely start before puberty.



SOURCE:

The Porphyrias

Anderson, Karl E

Cecil Textbook of Medicine,

13th ed. Mc Graw Hill,

1994.

+++++++++++++



Sometimes in AIP the level of salt (sodium and chloride) in the blood decreases

markedly and contributes to some of the AIP symptoms.



SOURCE:

Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

++++++++++



Measuring PBGD in red blood cells should not be relied upon by itself to exclude

AIP in a sick patient, because the enzyme is not deficient in red blood cells of all

AIP patients.



SOURCE:

Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

++++++++++++++





There are no differences in the latent and clinical phases of acute intermittent

porphyria between patients with lowered and those with normal porphobilinogen

deaminase.



SOURCE:

Heterogeneity of acute intermittent porphyria: a subtype with normal erythrocyte

porphobilinogen deaminase activity in Germany.

Gross U, Honcamp M, Doss MO.

Abteilung fur Klinische Biochemie

Klinikum der Philipps-Universitat Marburg

Deutschland.

European Journal of Clinical Chemistry & Clinical Biochemistry. 1996

Aug;34(8):613-8.

+++++++++++







Clinical and biochemical findings have shown that such can provoke the

neurologic manifestations of AIP.



SOURCE:

Neurologic manifestations of acute intermittent porphyria

Popova VN, Tsyganova AM.

Russia

Zh Nevropatol Psikhiatr Im S S Korsakova.

1971;71(4):541-4.

++++++++++++



Studies have found that 17-Oxosteroid conjugates in plasma and urine of

patients with acute intermittent porphyria.



SOURCE:

17-Oxosteroid in AIP.

Goldberg A. et. al.

Clin Sci Mol Med.

1974 Feb;46(2):207-22.

+++++++++







In AIP there has been found abnormal metabolism of steroid

hormones.



SOURCE:

A defect of steroid hormone metabolism.

Kappas A, et.al.

Fed Proc.

1972 Jul-Aug;31(4):1293-7

++++++++++++



In AIP there is most often an appearance of "port-wine" urine (PBG ->

porphobilin).



SOURCE:

The Porphyrias

Clinical Laboratory Studies

Biochemistry Department

School of Medicine

+++++++++







All porphyria patients with clinically manifest acute porphyria have elevated

SHBG ( Sex hormone-binding globulin) levels.



SOURCE:

Porphyria and sex hormones

Madejewicz S, Plachecka-Gutowska M.

Polish Archives of Medicine Wewn.

1966;37(3):349-50.

++++++++++++



In AIP urine collections there are often found brown pigments.



SOURCE:

The Porphyrias

Clinical Laboratory Studies

Biochemistry Department

School of Medicine

+++++++++





The porphyrin and porphobilinogen screens in AIP and if positive then

quantitative ALA, PBG, and porphyrins (which should be increased) are

definitive for AIP urine studies.



SOURCE:

The Porphyrias

Clinical Laboratory Studies

Biochemistry Department

School of Medicine

+++++++++







In AIP there is a defect in the reductive transformation of natural steroid

hormones in the hereditary liver disease.



SOURCE:

Studies in porphyria.

Kappas A, et. al.

J Exp Med.

1972 Nov 1;136(5):1043-53.

+++++++++



In blood serum studies in AIP patients there may be increased ALA, PBG.



SOURCE:

The Porphyrias

Clinical Laboratory Studies

Biochemistry Department

School of Medicine

+++++++++





The hereditary disorder acute intermittent porphyria is potentially fatal.



SOURCE:

Acute intermittent porphyria treated by testosterone implant.

Savage MW, et. al.

University of Manchester

Department of Medicine and Endocrinology

Hope Hospital, Salford, UK.

Postgraduate Medicine Journal

1992 Jun;68(800):479-81

+++++++++++





In blood serum studies in AIP patients there is often found

hypercholesterolemia.



SOURCE:

The Porphyrias

Clinical Laboratory Studies

Biochemistry Department

School of Medicine

+++++++++



In the 1966 "The Porphyrias" published in Scientific American journal the

following clinical and diagnostic features of AIP were published.





Acute females account for 63% of AIP patients.



General symptoms of AIP



90% experience abdominal pain.



87% experience abdominal tenderness



72 % experience red or dark urine



66% experience nonabdominal pain



61 % experience nausea & vomiting



56 % experience constipation



28% experience loss of appetite



23 % experience amenorrhea (absence of menses)



11 % experience breast secretions



9 % experience diarrhea





Neurologic symptoms of AIP



74% experience peripheral neuropathy



27% experience sensory disorder



16% experience respiratory paralysis



56 % experience behavorial change



40% experience irritability



40% experience anxiety



30 % experience hallucinations



30 % experience confusion



12 % experience seisure



28 % experience depressed or absent tendon reflexes



28% experience cranial nerve involvement





Physical findings of AIP





83 % experience red or dark urine



50 % experience tachycardia



44 % experience labile hypertension



31 % experience fever



24 % experience postural hypotension



12 % experience profused sweating



11 % experience hypertrichosis (hirsutism - excessive body hair)



8 % experience hyperpigmentation



46% experience muscle denevation



27 % experience dexreased nerve conduction velocity



SOURCE:

Scientific America

The Porphyrias

+++++++++



At the time of the acute attack, screening tests like the Hoesch or

Watson-Schwartz test for the detection of PBG inurine.



A positive screening test should always be confirmed by a quantitative test for

PBG in the urine.



SOURCE:

Acute Intermittent Porhyria

Anne LeMaistre, M.D.

1995

TMC

+++++++++++



During acute episodes of AIP, the production and urinary excretion of

delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) are increased.



SOURCE:

Porphyria Resources

United Medical Services



1996

++++++++++

A brown-red coloration i AIP is due to porphyrinogens reacting with light being

oxidized to porphyrins.



SOURCE:

Acute Intermittent Porphyria

J.W. Stevens et. al.

Anesthesia & Analgesia

Volume 82 No. 2

February 1996

+++++++++++



The most frequent symptoms were: abdominal pain,tachycardia, dark urine,

neurological and psychiatric alterations and arterial hypertension.





SOURCE:

Porphyric crisis: experience of 30 episodes (AIP)

Medicina

Buenas Aires

999;59(1):23-7

Morales Ortega X, et. al.

Departmento of Medicine

Occidente Hospital San Juan de Dios,

University of Chile, Santiago, Chile.

++++++++++



The 50% reduced activity of porphobilinogen deaminase (PBG-D) enzyme

found in AIP heterozygote persons is sufficient for basal conditions, but during

attacks, stimulation of haem synthesis upstream produces toxic spillover

products that give a purple color to the urine.



SOURCE:

Acute intermittent porphyria

Brekke OL. et. al.

Medisinsk avdeling Nordland Sentralsykehus 8092 Bodo.

Tidsskr Norwegian Laegeforen

2002 Apr 30;122(11):1102-5

++++++++++









Urinalysis in Acute Intermittent Porphyria (AIP) patients shows a "port-wine"

urine (PBG -> porphobilin) with brown pigments.



SOURCE:

The Porphyrias

Medical Handbook

1997

++++++++++++

TREATMENT



Treatment of AIP is based on large amounts of glucose administration for 4

days.



It is important to avoid precipitating factors such as drugs and fasting.



SOURCE:

The Porphyrias

Anderson, Karl E

Cecil Textbook of Medicine,

13th ed. Mc Graw Hill,

1994.

+++++++++



Administration of intravenous glucose

has proven effective for bringing

acute attacks under control.



SOURCE:

Diagnosis of acute intermittent

porphyria in northern Sweden:

an evaluation of mutation analysis

and biochemical methods.

Andersson C, Thunell S, Floderus et al

Journal of Internal Medicine

1995; 237: 301 8.

++++++++++





Heme deficiency in the liver of AIP patients stimulates an increase in

ALA-synthase which triggers an escalating metabolic chain reaction, leading to

an increase in the porphyrin content.



This reaction can be reduced by treating AIP patients with glucose.



SOURCE:

Effects of diabetes mellitus on patients with acuteintermittent porphyria

C. Andersson et. al.

Journal of Internal Medicine

Volume 245

Issue 2 Page 193 -

February 1999

++++++++++



High carbohydrate intake, glucose infusion or heme arginate are the first line of

treatment for the acute porphyrias.



SOURCE:

Treatment of Porphyria

Paul J.H. Wilson and Felix W.M. de Rooij

The Porphyrin Handbook

Volume 14 &#8211; Medical Aspects of Porphyrins

Porphyrins

(Chapters 85-96)

++++++++++



Two therapeutic approaches that may prove to reverse the fundamental disease

process, at least in some patients, involve [1] a high carbohydrate intake, and [2]

intravenous administration of hematin.



The latter, only recently introduced, is now being investigated with mixed results.



SOURCE:

Acute intermittent porphyria:

clinical and selected research aspects.

Tschudy DP, Valsamis M, Magnussen CR.

Annals of Internal Medicine

1975 Dec;

83(6):851-64.

++++++++



AIP treatment is based on large amounts of glucose administration for 4 days.



SOURCE:

Metabolic Disorders

Porphyrias: Clinical Manifestations, Diagnosis and Treatment

Bernardo Haddock Lobo Goulart & Samanta Teixeira Basto

University Medical School, Brazil

+++++++++



Treatment of AIP is based on large amounts of glucose administration

for 4 days.



It is important to avoid precipitating factors such as drugs and fasting.



SOURCE:

The Porphyrias

Cecil Textbook of Medicine,

13th ed. Mc Graw Hill,

1994.

+++++++++



The first therapeutic step in AIP is oral and/or parenteral administration of an

overload of carbohydrates and, if there was no response,

intravenous infusion of hematin is prescribed.



SOURCE:

Porphyric crisis: experience of 30 episodes (AIP)

Medicina

Buenas Aires

999;59(1):23-7

Morales Ortega X, et. al.

Departmento of Medicine

Occidente Hospital San Juan de Dios,

University of Chile, Santiago, Chile.

+++++++



The therapy for AIP is based on infusions of 10% glucose solution and

hydromineral imbalance correction.



SOURCE:

Acute intermittent porphyria

Sedlak T, Pontuch P, Duris I.

Univerzity of Komenskehov

Bratislava, Slovakia

Bratislava Lek Listy

1998 Oct;99(10):536-7

+++++++++



Acute attacks are treated with glucose intravenously.



SOURCE:

Acute intermittent porphyria

Brekke OL. et. al.

Medisinsk avdeling Nordland Sentralsykehus 8092 Bodo.

Tidsskr Norwegian Laegeforen

2002 Apr 30;122(11):1102-5

+++++++++









Treatment of AIP patients entails treating both the symptoms and the

complications, but also requires an endeavor to reverse the fundamental

disease by prescribing a carbohydrate-rich diet and by treating the attacks

with intravenous infusions of glucose.



SOURCE:

Beneficial Effect of Diabetes on

Acute Intermittent Porphyria

Folke Lithner, MD, PHD

Department of Internal Medicine

University Hospital, Umea, Sweden

Diabetes Care

2002; 25:797-798

++++++++++



The therapy for AIP is based on infusions of 20% glucose solution and

hydromineral imbalance correction.



SOURCE:

Acute intermittent porphyria

Sedlak T, et. al.

Bratislava Lek Listy, Slovakia

1998 Oct;99(10):536-7

+++++++++

Heme deficiency in the liver of AIP patients stimulates an increase in

ALA-synthase which triggers an escalating metabolic chain reaction,

leading to an increase in the porphyrin content.



This reaction can be reduced by treating AIP patients with glucose.



SOURCE:

Effects of diabetes mellitus on patients with acute intermittent porphyria

C. Andersson et. al.

Journal of Internal Medicine

Volume 245

Issue 2 Page 193 -

February 1999

++++++++++



A porphyria patient with lower extremity numbness, paresthesias, constipation,

urinary retention, and sexual dysfunction.



Laboratory evaluation confirmed a diagnosis of acute intermittent

porphyria (AIP).



A combination therapy of B-6 and glucose infusion was used.



SOURCE:

Acute intermittent porphyria with atypical neuropathy.

Goren MB, Chen C.

Department of Medicine, Fairfax Hospital, Va.

Southern Medical Journal

1991 May;84(5):668-9.

++++++++++



Carbamazepine



Porphyria resolves spontaneously after the withdrawal of carbamazepine

and sodium valproate and the commencement of parenteralnutrition with

subsequent carbohydrate loading.



SOURCE:

Variant acute intermittent porphyria in a child.

Badcock, N. R., G. D. Zoanetti, et al. (1990).

Clinical Chemistry 1990;

36(5): 812-4.

+++++++++



Hematin



+++++++++



Heme Arginate





+++++++++





Magnesium sulphate



The most important advantage of using magnesium sulphate in AIP patients is

that there has been no report in the literature of any magnesium-related increase

in ALA synthetase activity.



SOURCE:

Magnesium sulfate for AIP seizures.

Taylor, R. L.

Neurology

31(10): 1371-2. 1981

+++++++++++



Pain symptoms



Frequent doses of narcotic analgesia will usually treat pain associated with

Acute Intermittent Porphyria (AIP).



SOURCE:

The Porphyrias

Medical Handbook

1997

+++++++++++



Psychiatric symptoms



In a study done with an AIP patient, they found that the patient responded well

the the safety of trifluoperazine.



Although response and sensitivity to drugs may vary greatly among patients with

this porphyria, clinicians may want to consider the possibility of the this drug

to treat psychiatric symptoms in patients with acute intermittent porphyria.



SOURCE:

Clinical Pharmacological Therapy

1999 Sep;66(3):323-5

"Psychotropic drugs in acute intermittent porphyria."

Holroyd S, et. al.

Department of Psychiatric Medicine,

University of Virginia Health Sciences

Charlottesville VA

++++++++



AIP PROGNOSIS & MORTABLITY





The clinical course of acute porphyria is variable.



SOURCE:

Acute intermittent porphyria in a

children's psychiatric hospital.

Boon, F. F. and C. Ellis

J Am Acad Child Adolesc Psychiatry

1989; 28(4): 606-9.

++++++++++++



The prognosis is usually good if the disease is recognized and if treatment and

preventive measures are begun before severe nerve damage has occurred.



Although symptoms usually resolve after an attack, some patients develop

chronic pain.



SOURCE:



Dr. Karl E. Anderson

University of Texas Medical School

Galveston, TX

++++++++++++



The most important thing about AIP is to diagnose the disease at the onset.



If not, many severe complications may occur.



Even a lethal outcome in AIP is possible.



SOURCE:

Vojnosanit Pregl

2001 Jan-Feb;58(1):95-9

Acute intermittent porphyria as a problem in

differential diagnosis

Preradovic M, et. al.

+++++++++++++



AIP may run a serious invalidating and life-threatening course.



SOURCE:

Symptoms due to porphyria

Schattenberg AV et. al.

Ned Tijdschur Geneeskd

August 8; 142 1998

+++++++++++



The majority of AIP patients are free of symptoms during times of remission.



SOURCE:

Medicine Journal

February 22 2002

Volume 3, Number 2

"Acute intermittent porphyria"

+++++++++++





Most acute AIP patients are completely free of symptoms between attacks.



SOURCE:

"Acute intermittent porphyria"

Thomas G DeLoughery, MD

Associate Director

Department of TransfusionMedicine

Division of Clinical Pathology

Associate Professor

Department of Medicine

Division of Hematology and Medical Oncology

Oregon Health Sciences University

Portland, Oregon

++++++++++





Quality of life is lower in acute intermittent porphyria (AIP) than in other forms of

porphyria and a significant number of patients have major life event

consequences, e.g. failure to secure, or loss of, employment, limitation of family

size.



SOURCE:

Journal of Inherited Metabolic Disease

2001 Dec;24(7):733-47

Self-rated psychosocial consequences and quality of

life in the acute porphyrias.

Millward LM, Kelly P, Deacon A, Senior V, Peters TJ.

Department of Clinical Biochemistry,

GKT School of Medicine,

King's College, London, UK.

++++++++++



Most deaths in AIP occurr during the initial porphyric attack (20% of deaths)

or a subsequent attack (38% of deaths).



Suicide was also common.



The proportionate increase in mortality due to symptomatic AIP was three-fold

compared to the general population during the past 50 years.



The major cause of the increased mortality was the porphyric attack itself.



SOURCE:

American Journal of Medical Genetics

1996 Nov 1

65(4):269-73

"Mortality in patients with acute intermittent porphyria requiring hospitalization: a

United States case series"

Pierach Claus A,MD Bloomer Joseph R MN et.al.

Watson Laboratory,

University of Minnesota, Minneapolis, USA.

+++++++++++































































DISCLAIMER
PORPHYRIA FACTS is a medical education website dedicated to helping you focus your research on the inherited metabolic diseases known as the "Porphyrias".

PORPHYRIA FACTS is for individuals seeking information on Porphyria. The specific focus is on education, and research in the porphyrias.

PORPHYRIA FACTS present medical citations from medical professionals and others qualified and knowledgeable in the porphyrias.


PORPHYRIA FACTS takes no responsibility for medical information that is discussed here. You are encouraged to always seek medical advice before trying any new protocols. Open communication with your physician is important in developing effective treatment protocols.

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PORPHYRIA FACTS is a medical education website dedicated to helping you focus your research on the inherited metabolic diseases known as the "Porphyrias".

PORPHYRIA FACTS is for individuals seeking information on Porphyria. The specific focus is on education, and research in the porphyrias.

PORPHYRIA FACTS present medical citations from medical professionals and others qualified and knowledgeable in the porphyrias.


PORPHYRIA FACTS takes no responsibility for medical information that is discussed here. You are encouraged to always seek medical advice before trying any new protocols. Open communication with your physician is important in developing effective treatment protocols.