In-born Errors of Metabolism

Question 1

What is deficient in G6PD?

Answer 1

Glucose-6-Phosphate Dehydrogenase: RBCs cannot phosphorylate glucose => cannot carry out glycolysis => hemolyze

Question 2

What is seen on microscopy in G6PD?

Answer 2

Heinz bodies = denatured hemoglobin

Question 3

What exacerbates G6PD?

Answer 3

Fava beans, other oxidative stressors

Question 4

What is pyruvate kinase deficiency?

Answer 4

No pyruvate kinase => cannot finish glycolysis to make ATP or make Krebs’ cycle reactants

Question 5

Explain essential fructosuria?

Answer 5

Deficiency in fructokinase (Fructose => F1P conversion) => benign condition

Question 6

Explain hereditary fructose intolerance?

Answer 6

Deficiency in F1P aldolase (F1P => DHAP, glyceraldehyde) => severe hypoglycemia upon sucrose or fructose ingestion

Question 7

Explain galactosemia.

Answer 7

Deficiency in galactokinase (Galactose => Gal-1-P) => causes early cataract formation

Question 8

Explain severe galactosemia.

Answer 8

Deficiency in gal-1-phosphate uridyl transferase (Gal-1-P => Glucose-1-P) => growth and mental retardation and possibly early death

Question 9

Explain phenylketonuria

Answer 9

Deficiency of phenylalanine hydroxylase => inability to do phenylalanine -> tyrosine conversion => no catecholamines, melanin, thyroxine => excess phenylketones

Question 10

Explain Hartnup disease pathophysiology

Answer 10

Defect in intestinal and renal transporters for neutral amino acids => symptoms due to loss of tryptophan (nicotinamide precursor) => mimic niacin (B3) deficiency (pellagra)

Question 11

Explain Hartnup disease presentation and treatment

Answer 11

Pellagra-like skin lesions and neurologic manifestations ranging from ataxia to frank delirium
Replace niacin and provide high-protein diet with nicotinamide supplements

Question 12

Explain cystinuria pathophysiology

Answer 12

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

Question 13

Explain PKU clinical presentation

Answer 13

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

Question 14

Explain PKU treatment

Answer 14

Restriction of dietary phenylalanine (aspartame)

Increase dietary tyrosine

Question 15

Explain albinism pathophysiology and presentation

Answer 15

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

Question 16

Explain pathophysiology and presentation of homocystinuria

Answer 16

Cystathionine synthase deficiency => excess homocystine
Present with MR, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), atherosclerosis (stroke, MI)

Question 17

Explain diagnosis and treatment of homocystinuria

Answer 17

Measure excess homocystine in urine without B12 deficiency

Decrease dietary methionine and increase dietary cysteine OR vitamin B6

Question 18

Explain Maple Syrup Urine disease pathophysiology, presentation, diagnosis, treatment

Answer 18

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