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Flashcards in Post Midterm Diseases Deck (31):


Symptom: Moussey urine
Accumulation of: Phenylalanine and
phenylpyruvic acid
Enzyme deficiency: PAH if classic
BH2 Reductase if malignant
Dietary restriction and TTO: PHE



Symptom: Black Urine
Accumulation of: Homogentistic acid
Enzyme deficiency: Hongentistis acid oxidase
Dietary restriction/TTO: Benign so no TTO


Tyrosinemia type 1

Symptom: Cabbage like urine
Accumulation of: Fumaryl acetoacetic acid
Enzyme deficiency: Fumaryl acetoacetic acid Hydroxylase
Dietary restriction/TTO: PHE and TYR


Maple Syrup Urine Disease (MSUD)

Symptom: Maple syrup urine
Accumulation of: B C Acids
Enzyme deficiency: BCKD
Dietary restriction/TTO: Restrict I,L,V,
give TPP (Vitamin B1)


Methylmalonic Aciduria

Symptom: Methylmalonic acid in urine
Accumulation of: Methylmalonic acid
Enzyme deficiency: B12 Cofactor of Methylmalonic acid mutase


Lesch-Nyhan Syndrome

X-linked. Deficiency of the enzyme hypoxythine-guanine phosphoribosyltransferase (HGPRT). Results in an inability or salvage purines hypoxanthine and guanine. End product of degradation is uric acid (excess found in urine) (baby diaper: orange crystals)
Causes: severe mental retardation, self-mutilation, involuntary movements, and gout.
Causes increased PRPP levels and an increased in de novo purine synthesis.


Severe Combined Immunodeficiency Syndrome (SCIDS)

cause: Adenosine deaminase (ADA) deficiency.
DNA is not synthesized in T-cells and B-cells b/c of an accumulation of dATP. (Lymphocytopenia: T-cell and B-cell depletion.) (dATP is an inhibitor of ribonucleotide reductase, and therefore, of DNA synthesis.


PNP Deficiency

Purine nucleoside phosphorylase (PNP) deficiency causes impairment of T-cell fxn.
Characterized by decreased uric acid production and increased purine nucleosides and nucleotides.



Characterized by hyperuricemia; acute arthritic joint inflammation caused by deposition of uric acid crystals.

Can be diagnosed by presence of negatively birefringent monosodium urate crystals in aspirated synovial fluid examined by polarized-light microscopy

Affects men and women of any age


Primary Gout

Genetic and mainly affects males over 30 years old.


Secondary Gout

Brought on by a number of disorders including leukemia, polycythemia, HGPRT deficiency, cancer treatment with antimetabolites, or chronic renal insufficiency.


Acute Intermittent Porphyria

Deficient enzyme: HMB synthase (porphobilinogen deaminase)
Autosomal dominant disorder.
Result: ALA activity is high as ALA synthase is not feed-back inhibited by heme/hemin and instead enzyme synthesis is activated @ low heme/hemin (derepression).
Characterized by: ALA and Porphobilinogen in blood and urine.

--AIP occurs in pts who are treated with specific drugs that inhibit cytochrome p450 synthesis. Can also be triggered by infections, ethanol abuse or abnormal estrogen metabolism.



Acute Intermittent Porphyria Signs and Symtoms

-very severe abdominal pain
-highly agitated state, tachycardia, respiratory problems, nausea
-confusion, mental disturbances
-lower extremity weakness
-pts NOT photosensitive, however ALA and porphobilinogen accumulate at high levels and can act as neurotransmitters.


Acute Intermittent Porphyria detection

Porphobilinogen in urine can be detected by rapid dipstick method. Later on, ALA and porphobilinogen conc can be measured in lab.
-Normal urine color changes to dark purple after 24 exposure to light and air.
-Colorless porphobilinogen changed to dark colored porphobilin.


Acute intermittent Porphyria treatment

Treatment: pain medication, intavenous glucose and saline infusion and it can include intravenous hemin admin in severe cases.

DO NOT admin barbituates to calm pt. down, as stimulation of CYP450 synthesis can worsen situation and even lead to death.


Congenital Erythropoietic Porphyria

Deficient enzyme: Uroporphyrinogen III Synthase (erythroid-cell specific)
Autosomal recessive
Characterized by: Uroporphyrin I and Coproporphyrin I in tissues, blood and urine (red)
Onset in childhood or earlier
-Most severe photosensitivity.

-Hydroxymethylbilane spontaneously forms uroporphyrinogen I


Congenital Erythropoietic Porphyria Signs and Symptoms

-Extremely painful photosensitivity
-Severe damage to skin beginning in childhood
-Blister, poor wound healing
-Hypertrichosis is often severe
-can include reddish-brown teeth
-"werewolf" features, hairy front and arms.


Congenital Erythropoietic Porphyria Treatment

Treatment: Bone marrow transplantation

- hemin infusion would not help, erythroid cells contain ALAS2 which is not inhibited by hemin.


Porphyria Cutanea Tarda (PCT)

Deficient Enzyme: Uroporphyrinogen III decarboxylase
2 types:
Type I - sporadic, 80%
Type II - familial, autosomal dominant trait, 20%
Characterized by: Uroporphyrin III in tissues (cutaneous lesions - skin and liver), blood, and urine (red).

- Erosions and bullous lesions in sun-exposed areas of the patients are produced by minor trauma b/c of increased skin fragility. These lesions heal with scarring, pigment changes, and formation of small white papules.


- Most common porphyria and a chronic disease of liver. Liver damage can lead to acquired PCT (hepatitis, ethanol abuse)

-Clinical expression influences by various other factors, like hepatic iron overload or sunlight.


Porphyria Cutanea Tarda (PCT) treatment

Treatment: avoidance of sun-light, alcohol and iron.


ALA Dehydratase Porphyria

Lead poisoning of ALA dehydratase and ferrochelatase
Autosomal recessive
Leads to anemia.
-DOES NOT leave to photosensitivity.

-Lead interacts with Zinc cofactors for ALA dehydratase and ferrochelatase. ALA and protoporphyrin IX accumulate in urine


Carcinoid Syndrome

Tumor of APUD cells (GI tract)
leads to increase of Serotonin (5-hydroxytrypamine).
- 5-HIAA (hydroxyinandol acetic acid) in urine

Symptoms: Diarrhea, sweating, cutaneous flushing, bronchospasm


Crigler-Najjar syndrome I

-Inherited hyperbilirubinemia
-almost complete deficiency of microsomal bilirubin glucuronyl transferase (most severe)
- Serum bilirubin levels can reach up to 50 mg/dL (unconjugated hyperbilirubinemia) and results in kernicterus and mental retardation.
Management: daily phototherapy, exchange transfusion and prevention of kernicterus
-usually fatal by 2 yr/old if not treated.


Crigler-Najjar syndrome II (Arias syndrome)

-Characterized by lower activity of bilirubin glucuronyl transferase (10-20% of normal)
-Jaundice (but less severe than type 1)
-(unconjugated) Inherited hyperbilirubinemia
-Serum bilirubin levels: 6-22mg/dL
-Children respond to phenobaribital (induces enzyme)
- Regular phototherapy used in pts with persisting high bilirubin levels.


Gilbert's Syndrome

-Inherited Hyperbilirubinemia (mild increase in unconjugated)
- mild jaundice (2-5mg/dL) usually following infection, stress or starvation.
- UDP-glucuronyl transferase activity is about 50%


Dubin-Johnson syndrome

-Inherited hyperbilirubinemia
-inherited deficiency of ABC transporter that transports conjugated bilirubin from the hepatocyte into biliary canaliculus
-elevated levels of conjugated (direct) bilirubin in circulation.


Hemophilia (A and B)

-Inherited (X-linked recessive) coagulation disorder
-Defect in intrinsic coagulation pathway (inc. clot time and inc. APTT)
-Easy to bruise
-Massive hemorrhage after trauma/surgery
-Spontaneous hemorrhages, particular in joints (hemarthrosis)

Hemophilia A - Factor VIII deficiency
Hemophilia B - Factor IX deficiency


Von Willebrand Disease

-Most common inherited (dominant or recessive) bleeding disorder
-Defect either qualitative or quantitative
-Instability of factor VIII (may result in APTT)
Clinical features: (sim to Hemo A)
-Inc. mucosal bleeding
-Inc. post-op bleeding

Lab findings:
-Bleeding time = prolonged
-APTT= prolonged
-vWF levels= low



- Inc bleeding time due to platelet plug formation
-Quantitative defect
-Low platelet count


Bernard-Soulier Syndrome

-Bleeding disorder: Platelet plug formation defect (qualitative)
-Normal platelet count and INCREASED bleeding time
-GpIb defect


Thrombasthenia of Glanzman and Naegeli

-Bleeding disorder: Platelet plug formation defect (qualitative)
-Normal platelet count and INCREASED bleeding time
-GpIIb/IIIa defect