Diseases Flashcards

Question

Classical Galactosemia

Answer 1

GALT Deficiency - Autosomal recessive disorder (1:30,000 births) - Galactosemia, galactosuria, vomiting, diarrhea, jaundice - Hyperuricemia - Accumulation of Gal-1-P and Galactitol in nerve, lens, liver, kidney tissue • Liver damage • Severe mental retardation • Cataracts - Treatment: rapid diagnosis + removal of galactose (lactose) from diet

Answer 2

- Dihydropteridine Reductase: ○ Normally catalyzes: Dihydrobiopterin --> THB (Tetrahydrobiopterin) ○ THB is required cofactor for 3 major reactions 1. Phenylalanine --> Tyrosine (hydroxyphenylalanine) 1) Catalyzed by: Phenylalanine Hydroxylase 2. Tyrosin --> DOPA (dihydroxyphenylalanine) 1) Catalyzed by: Tyrosine Hydroxylase 3. Tryptophan --> Serotonin 1) Catalyzed by: Tryptophan Hydroxylase - Defect in Dihydropteridine Reductase will IMPAIR ALL 3 REACTIONS!!

Answer 3

HGPRT Deficiency X-linked recessive HGPRT Deficiency - Inability to salvage hypoxanthine or guanine - ↓IMP and ↓GMP lead to ↑de novo purine synthesis ``` Neurological deficits: • Spasticity • Mental retardation • Aggression • Self-mutilation - ↑PRPP - ↑hypoxanthine - ↑guanine - ↑de novo purine biosynthesis (PRPP feed-forward) - ↑uric acid buildup --> GOUT - ↓dopaminergic neurons ↓dopamine ```

Answer 4

ADA Deficiency - ↑dATP (severe excess) - No cell division (neg feedback of dATP on RNR reductions) - Severe lack of B & T lymphocytes (combined immunodeficiency) - Predisposes patients to severe bacterial, viral, opportunistic infections early in life - Often fatal - Can be treated with BMT (bone marrow transplant) with or without gene therapy - Enzyme replacement Therapy - Prophylaxis: intravenous IgG • Used for the immunodeficiencies

Answer 5

PNP deficiency - T-cell deficiency (selective immunodeficiency) - Recurrent bacterial, viral, and opportunistic infections - Bone marrow transplant

Answer 6

- Orototate Phosphoribosyl Transferase deficiency or - Orotidylate Decarboxylase deficiency - Megaloblastic anemia - ↑Orotate in the urine - Supplement with CMP, UMP, URIDINE OR CYTIDINE - B9 or B12 supplementation will NOT be effective

Answer 7

○ Single gene defect in Phosphotransferase*** § Affects ALL LYSOSOMES IN THE BODY*** ○ Caused by deficiency of ability to phosphorylate mannose (marker for lysosomal residency) ○ Acid hydrolases are now instead secreted into extracellular media ○ Leads to substance build up in the lysosome and characteristic "inclusion cell" phenotype - Skeletal abnormalities - Restricted joint movement - Coarse (dysmorphic) facial features - Severe psychomotor impairment - Death usually occurs by 6 years of age - Diagnostic: Acide hydrolases in blood sample ○ Acide hydrolases are normally only found in lysosomes ○ In I-cell patients the enzymes are now instead found in high concentrations in the blood

Answer 8

- PKU can be due to mutation in Phenylalanine Hydroxylase - PKU can be due to mutation in Dihydrobiopterin Reductase - Phenylalanine (essential AA) is converted to Tyrosine - Normal pathway: Phenylalanine --[Phenylalanine Hydroxylase]--> Tyrosine --> Fumarate + Acetoacetate ○ THB (Tetrahydrobiopterin): COFACTOR for Phenylalanine Hydroxylase

Answer 9

- Transporter protein problem - Blue Diaper Syndrome: failure to absorb Tryptophan in the Intestine ○ Tryptophan --> hydrolyzed by bacterial enzymes to form Indole (blue color)

Answer 10

○ Disorder of the kidney proximal tubules reabsorption of filtered cysteine and dibasic AA's (Lysine, Ornithine, Arginine) ○ Inability to reabsorb cystine leads to accumulation and prcipitation of cystine STONES in urinary tract ○ KIDNEY STONES

Answer 11

- Fluid filled sacs form in the kidney --> initiated in the neprhon then grow larger --> break off and continue to expand --> massive enlargement of the kidney - Leads to Kidney damage --> ↑urea in circulation --> ↑AMMONIA TOXICITY - ↑AMMONIA TOXICITY - Inability to reabsorb amino acids in the urine

Answer 12

- Degeneration of cells in the substantia nigra causes LOSS OF DOPAMINE - Patients are treated with L-DOPA to increase dopamine levels - Efficacy of L-DOPA treatment diminishes over time due to progressive loss of cells in the substantia nigra

Answer 13

``` Hypoketotic Hypoglycemia NORMAL lactate NORMAL ammonia NORMAL carnitine NORMAL ACYLCARNITINE NORMAL FFA These kids are normal; no developmental defect. But fasting or infection can initiate the disease ```

Diseases Flashcards

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