Metabol 5) Inborn errors of metabolism Flashcards
What are the management principles for inborn metabolic disorders?
Special diets Peritoneal or haemodialysis Administer deficient metabolite Administer deficient enzyme Administer cofactor or coenzyme Activate alternative pathways Bone marrow or liver transplant
What categories of inborn metabolic disorders are there?
Amino acid disorders Carbohydrate disorders Lipid, fatty acid and organic acid disorders Purine and pyramiding disorders Haem disorders Lysosomal storage disorders Mitochondrial disorders Peroxismal disorders
Give examples of amino acid disorders
Transport disorders - dibasic amino acids (cystinuria) - neutral amino acids (Hartnup disease) Metabolism - phenylalanine / tyrosine - urea cycle defects
What is cystinuria?
Defective cystine transporter
Cystine in urine crystallises to form stones
What is the management for cystinuria?
Symptomatic treatment
Prevent stone formation - water intake, alklaisation
Lithotripsy, chelation
Describe the features of phenylketonuria
Normal at birth Gradually develop neuropsychological problems - microcephaly, low IQ - seizures, tremor - impaired myelination Blonde hair Musty odour
What is the management for phenylketonuria?
Diet
L-DOPA, 5-HT
BH4
What are the signs of urea cycle defects?
Lethargy Poor feeding Seizures Coma Death
What is the management for urea cycle defects?
Reduction of dietary protein intake Removal of excess toxic products Removal of excess precursors Replacement of intermediates in urea synthesis Liver transplant
Give examples of carbohydrate disorders
Glycogen storage disorders - liver - GSD-1 - muscle - McArdle, Pompe Galactose - galactosemia Fructose - fructose intolerance Gluconeogenesis Pyruvate Pentose
What are the features of GSD-1?
Hypoglycaemia Lactic acidosis Lipidaemia Hepatomegaly Uricaemia Neutropenia Bruising Renal disease
What is the management of GSD1?
Continuous feeds or corn starch Limit other sugars Inhibit uric acid production High cholesterol Liver transplant
What is galactosaemia?
GAL1PUT deficiency (galactose 1 phosphate uridyl transferase)
What are the features of galactosemia?
Prolonged jaundice
Cataracts
Poor weight gain
Hepatomegaly
What is the management of galactosemia?
Galactose free diet
Soy milk
Describe MCAD deficiency
Hypoglycaemia when unwell or fasting
Unable to mobilise fatty acids and ketones when low glucose.
Reduced total carnitine, reduced free carnitine / acyl carnitine ratio
Elevated medium-chain acylcarnitines
What is the management of MCAD deficiency?
Avoid fasting
Slow release carbohydrates
Supplement carnitine
Riboflavin
What are lysosomes?
Spherical vesicles containing over 50 hydrolytic enzymes
Break down biomolecules
What are the features of mucopolysaccharidoses?
Coarse facies Mental retardation Short stature Contractures Dysostosis Multiplexa
Give examples of mucopolysaccharidoses disorders
Hurler
Hunter
Sanfillippo
Give examples of lipid storage disorders
Gangliosidosis Tay sachs Gaucher Niemann-pick Muclipidoses Lipofuscinosis
What are the consequences of mitochondrial disorders?
Respiratory chain defects
Brain, eye, heart and muscle problems
Describe peroxisomal disorders
Production and decomposition of peroxide
Accumulation of VLCFA in adrenal glands and peripheral nerves
