In-born Errors of Metabolism Flashcards
What is deficient in G6PD?
Glucose-6-Phosphate Dehydrogenase: RBCs cannot phosphorylate glucose => cannot carry out glycolysis => hemolyze
What is seen on microscopy in G6PD?
Heinz bodies = denatured hemoglobin
What exacerbates G6PD?
Fava beans, other oxidative stressors
What is pyruvate kinase deficiency?
No pyruvate kinase => cannot finish glycolysis to make ATP or make Krebs’ cycle reactants
Explain essential fructosuria?
Deficiency in fructokinase (Fructose => F1P conversion) => benign condition
Explain hereditary fructose intolerance?
Deficiency in F1P aldolase (F1P => DHAP, glyceraldehyde) => severe hypoglycemia upon sucrose or fructose ingestion
Explain galactosemia.
Deficiency in galactokinase (Galactose => Gal-1-P) => causes early cataract formation
Explain severe galactosemia.
Deficiency in gal-1-phosphate uridyl transferase (Gal-1-P => Glucose-1-P) => growth and mental retardation and possibly early death
Explain phenylketonuria
Deficiency of phenylalanine hydroxylase => inability to do phenylalanine -> tyrosine conversion => no catecholamines, melanin, thyroxine => excess phenylketones
Explain Hartnup disease pathophysiology
Defect in intestinal and renal transporters for neutral amino acids => symptoms due to loss of tryptophan (nicotinamide precursor) => mimic niacin (B3) deficiency (pellagra)
Explain Hartnup disease presentation and treatment
Pellagra-like skin lesions and neurologic manifestations ranging from ataxia to frank delirium
Replace niacin and provide high-protein diet with nicotinamide supplements
Explain cystinuria pathophysiology
Defect in kidney tubular reabsorption of basic amino acids => high level of basic AA excretion => low solubility of cysteine leads to precipitation and kidney stone formation
Increase urine volume and alkalization
Explain PKU clinical presentation
MUSTY BODY ODOR
Infants 6-12 mos present with CNS symptoms of developmental delay, seizures, failure to thrive
Hypopigmentation => fair hair, blue eyes, pale skin
Explain PKU treatment
Restriction of dietary phenylalanine (aspartame)
Increase dietary tyrosine
Explain albinism pathophysiology and presentation
Lack of migration of neural crest cells => deficiency in tyrosinase/tyrosine transporters (deficient conversion to melanin)
Present: Neonates with amelanosis = white hair, pale skin, gray-blue eyes
Nystagmus, photophobia
Diagnose by iris translucency and presentation
Explain pathophysiology and presentation of homocystinuria
Cystathionine synthase deficiency => excess homocystine
Present with MR, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), atherosclerosis (stroke, MI)
Explain diagnosis and treatment of homocystinuria
Measure excess homocystine in urine without B12 deficiency
Decrease dietary methionine and increase dietary cysteine OR vitamin B6
Explain Maple Syrup Urine disease pathophysiology, presentation, diagnosis, treatment
Deficient a-keto acid dehydrogenase => no degradation of branched-chain amino acids
Normal at birth => develop characteristic odor, lethargy, feeding difficulties, coma, seizures => CNS defects, MR, death
Diagnose with high levels of branched-chain AAs
Treat with dietary restriction of branched-chain AAs
