Inborn Errors of Metabolism 2

Question 1

What is Cystinuria

Answer 1

clinical present: cystine renal stones

biochemical defect : defective absorption of cystine and dibasic amino acids- results in accumulation and precipitation of stones of cystine in the urinary tract

Genetics: mutation in the SLC3A1 gene

Diagnose= AAurine - high cystine and arginine content, but normal AA in the plasma

Question 2

what inborn errors of metabolism are associated with glucose metabolism?

Answer 2

Pyruvate Carboxylase deficiency - diagnose based on increase in lactate and ketosis - severe in neonatal (coma, lactic acidosis)= pyruvate is converted to lactic acid instead of acetyl coA even in aerobic conditions

Fructose 1,6 bisphosphate deficiency

PEP carboxykinase deficiency (rare)

Question 3

what biomarkers do we use to diagnose glucose metabolic disorders?

Answer 3

• pyruvate carboxylase deficiency: buildup of lactate
• F1,6Bisphosphate deficiency: buildup of lactate
• PEP carboxykinase deficiency: proabaly lactate

**use lactate and ketosis to diagnose metabolic disorders*

Question 4

how does the maternal mode of inheritance influence the clinical presentation of mitochondrial respiratory chain disorders?

Answer 4

The mitochondrial RC is composed of approximately 100 different proteins. Only 13 of the proteins are encoded by mitochondrial genes; the others are encoded by nuclear genes. All complexes of the RC except complex II have a double genetic origin, and one to seven subunits of these complexes are mitochondrially encoded

Therefore, a genetic mutation of the maternal mitochondrial DNA would effect only a portion of the respiratory chain -

Question 5

Describe disorders of fatty acid oxidation involving medium chain length fatty acids

Answer 5

Medium-chain acyl-coenzyme a dehydrogenase deficiency (MCADD)

• disorder of fatty acid oxidation due to impaired break down of medium chain fatty acids
• MCAD is responsible for the dehydrogenation step of fatty acids with chain lengths between 6-12 carbons -

symptoms= hypoketotic (decresed acetyl coA) hypoglycemia (tissues rely on glucose), liver dysfunction

Question 6

What are the two main types of peroxisomal disorders?

Answer 6

1. defect in peroxisome assembly
2. peroxisome biogenesis disorders (PBD) - failure to make functioning peroxisomes (Zellweger syndrome and infantile refsum’s disease)