34. Inborn Errors of Metabolism 1 Flashcards
What are the metabolic consequences of impaired enzyme activity?
Deficiency of a product
Accumulation of substrate
Conversion to an alternative product
What is PKU caused by?
Autosomal recessive disorder
PAH enzyme defect or defective synthesis of cofactor
Clinical symptoms of PKU
Irritability Vomiting Seizures Mental retardation by 4-6 months Reduced melanin production Eczema
Management of PKU
Diet low in phenylalanine
Supplement with tyrosine
What is tyrosinaemia caused by?
Deficiency in fumarylacetoacetate hydrolase
Accumulation of fumaryl acetoacetate in urine
Symptoms of tyrosinaemia
urine has cabbage-like odour
Liver failure
Renal tubular acidosis (acid blood)
Treatment of tyrosinaemia
Dietary restriction of phenylalanine and tyrosine
Nitisonone drug
What is aciduria?
Accumulation of organic acids in blood and urine
What does MCADD stand for?
Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency
What is MCADD?
Disorder of fatty acid oxidation due to impaired break down of medium-chain fatty acids into acetyl-CoA
Symptoms of MCADD?
Hypoketotic hypoglycaemia Liver dysfunction SID Lethargy Seizures Coma Intolerance to fasting
What are the clinical manifestations of alkaptonuria?
Dark urine
Ochronosis: pigmentation of eyes and ears
Arthritis caused by calcification
What is the defect in maple syrup urine disease?
Metabolism of leucine, isoleucine, valine
What are the symptoms of maple syrup urine disease?
Progressive lethargy
Weight loss
Maple syrup odour to urine
Ketosis, coma, death
What is the treatment of maple syrup urine disease?
Dietary restriction of branched chain amino acids
What is the defect in homocystinuria?
Defect in cystathionine synthase
Accumulation of homocysteine in the urine
Methionine and metabolites elevated in the blood
What are the symptoms of homocystinuria?
Cardiovascular disease Deep vein thrombosis Stroke Mental retardation Osteoporosis Dislocation of lens
What are the dibasic amino acids?
Cysteine
Ornithine
Arginine
Lysine
Name 4 disorders of amino acid transport
Cystinuria
Lysinuric protein intolerance
Hartnup disease
Iminoglycinuria
How does cystinuria present?
Cystine renal stones
Dibasic amino acids in urine
What defect causes cystinuria?
Defective absorption of cystine and dibasic amino acids
What is the treatment of cystinuria?
High fluid intake
Alkalisation of urine with sodium bicarbonate
What is the clinical presentation of lysinuric protein intolerance?
Failure to thrive Poor apetite Protein aversion Hyperammonaemia with progressive encephalopathy Renal failure Osteoporosis
What defect causes lysinuric protein intolerance?
Impaired function of urea cycle and lysine deficiency
What happens to the plasma in lysinuric protein intolerance?
Increased ammonia
Decreased Arg, Lys, Orn
What happens to the urine in lysinuric protein intolerance?
Increased ARg, Lys, Orn
What is the treatment of lysinuric protein intolerance?
Protein restriction
Citrulline replacement to enhance urea cycle
