Purine and pyrimidine metabolism disorders Notes

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This Osmosis High-Yield Note provides an overview of Purine and pyrimidine metabolism disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Purine and pyrimidine metabolism disorders:

Lesch-Nyhan syndrome

Orotic aciduria

NOTES NOTES PURINE & PYRIMIDINE METABOLISM DISORDERS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Enzymatic disorders in biochemical pathways crucial for biosynthesis of nucleobases → impaired nucleotide formation ▫ Adenosine triphosphate (ATP), guanosine monophosphate (GMP) ▪ Inherited conditions SIGNS & SYMPTOMS ▪ Disease-specific ▪ Lesch–Nyhan syndrome ▫ Kidney stones, hematuria, urinary tract infections (UTIs), arthritis, tophi ▫ Spasticity, chorea, hyperactive reflexes, grimacing, dystonia ▫ Intellectual impairment, developmental delay, self mutilation, lack of speech, compulsions ▪ Orotic aciduria ▫ Glossitis, growth failure, developmental delay, intellectual disability, congenital malformation, immunodeficiency 292 OSMOSIS.ORG DIAGNOSIS LAB RESULTS ▪ No activity in one enzyme, excess in one metabolite OTHER DIAGNOSTICS ▪ Clinical evaluation, genetic testing TREATMENT MEDICATIONS ▪ Lesch–Nyhan syndrome ▫ Xanthine oxidase inhibitors, benzodiazepines, baclofen, gabapentin, neuroleptics OTHER INTERVENTIONS ▪ Lesch–Nyhan syndrome ▫ Lithotripsy, protecting devices ▪ Orotic aciduria ▫ Pyrimidine replacement therapy
Chapter 51 Purine & Pyrimidine Metabolism Disorders LESCH–NYHAN SYNDROME osms.it/lesch-nyhan_syndrome PATHOLOGY & CAUSES ▪ Rare disease; excess of uric acid CAUSES ▪ Behavioural, cognitive ▫ Intellectual impairment, developmental delay, self-mutilation (e.g. finger, lip biting), lack of speech, compulsions (e.g. spitting) ▪ X-linked recessive mutation in HPRT gene → lack of enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) ▪ Decreased HGPRT activity, recycling of cell waste products → increased transformation of cell waste products into uric acid → increased uric acid LAB RESULTS COMPLICATIONS OTHER DIAGNOSTICS ▪ Uric acid precipitation in urine → urate stones in kidney, ureter, bladder → renal failure ▪ Uric acid deposition in joints → gout-like arthritis (AKA juvenile gout) ▪ Central nervous system (CNS) alterations, may be due to ▫ Uric acid accumulation → oxidative damages ▫ Decreased nucleotide production → decreased dopamine production → lesions in striatal dopaminergic pathways ▪ Insufficient vitamin B12 → megaloblastic anemia SIGNS & SYMPTOMS DIAGNOSIS ▪ HGPRT activity in blood, other tissues ▪ Increased urate-to-creatinine ratio in urine ▪ Hyperuricosuria, hyperuricemia ▪ Clinical evaluation, genetic testing TREATMENT MEDICATIONS ▪ Xanthine oxidase inhibitors to reduce production of uric acid ▪ Benzodiazepines, baclofen for neurological issues ▪ Benzodiazepines, gabapentin, neuroleptics for behavioural issues OTHER INTERVENTIONS ▪ Lithotripsy for kidney stones ▪ Protecting devices for behavioural issues ▪ Uric acid hyperproduction ▫ Urate precipitation in urinary tract: “orange sand” deposits in diapers of infants; kidney stones → hematuria, UTIs ▫ Arthritis, tophi ▪ Neuromuscular ▫ Spasticity, chorea, hyperactive reflexes, grimacing, dystonia OSMOSIS.ORG 293
OROTIC ACIDURIA osms.it/orotic-aciduria PATHOLOGY & CAUSES ▪ Extremely rare disease; alteration in pyrimidine synthesis → excessive excretion of orotic acid (intermediate metabolite) in urine CAUSES ▪ Autosomal recessive disease ▪ Defect in activity of uridine monophosphate synthetase (UMPS) → decreased UTP production and increased dihydroorotate accumulation ▫ Type 1: both enzymes affected; orotidine monophosphate decarboxylase (OMP-decarboxylase), orotate phosphoribosyltransferase (OPRT) ▫ Type 2: only OMP-decarboxylase affected COMPLICATIONS ▪ Decreased production of pyrimidin, cofactors needed for erythropoiesis → megaloblastic anemia unresponsive to vitamin B12 supplementation, folic acid SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ ▪ 294 OSMOSIS.ORG Glossitis Growth failure Developmental delay Intellectual disability Congenital malformation Immunodeficiency DIAGNOSIS LAB RESULTS ▪ Anemia ▪ Orotic acid dosage in urine OTHER DIAGNOSTICS ▪ Clinical evaluation TREATMENT OTHER INTERVENTIONS ▪ Pyrimidine replacement therapy ▫ Uridine monophosphate

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Purine and pyrimidine metabolism disorders essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Purine and pyrimidine metabolism disorders by visiting the associated Learn Page.