metabolic 5: inborn errors of metabolism Flashcards
what are some common characteristics of inborn errors of metabolism?
Often under-diagnosed Normal at birth Nature of mutation – varies Symptomatic later Exacerbated by diet or illness Mimics sepsis, without known risk factors Many patients can lead a normal life If diagnosed & treated early Before irreversible damage to organs
what type of inheritance is most common and why?
autosomal recessive due to consanguinity
what is cysteinuria ?
Defective cystine transporter
Cystine in urine – crystallises to form stones
how is cysteine uria managed?
Management
Symptomatic treatment
Prevent Stone formation – water intake, alkalisation
Lithotripsy, Chelation
what is phenylketonuria and its features?
Normal at birth Gradually Neuropsychological problems Micreocephaly, Low IQ Seizures, Tremors Impaired myelination Blonde hair Musty odour
how is phenylketonuria managed?
Management:
Diet
L-DOPA, 5-HT
BH4
what are the symptoms and signs of urea cycle defect?
Soon after birth; if untreated, fatal
Lethargy, poor feeding, seziures, coma, death
High Ammonia – ammonia intoxication
how is UCD managed?
Reduction of dietary protein intake
Removal of excess toxic products
Levulose (Ammonia)
Removal of excess precursors
Na benzoate (glycine), Na phenylbutyrate (glutamate)
Replacement of intermediates in urea synthesis
Citrulline, Arginine
Forces available enzymes to maximal activity
Liver transplant
what is glucose 6 phosphatase 1 deficiency?
Glucose 6 phosphatase deficiency
Key enzyme in gluconeogenesis
Hypoglycaemia, lactic acidosis, lipidaemia, hepatomegaly, uricaemia
Neutropenia, bruising, renal disease
how is GSD1 managed?
Continuous feeds or corn starch (slow absorption)
Limit other sugars – fructose, galactose, sucrose, maltose
Inhibit uric acid production – Allopurinol
High cholesterol – Statins
Liver transplant
what is galactosemia?
signs and symptoms?
management ?
GAL1PUT deficiency
Galactose 1 Phosphate Uridyl Transferase
Prolonged jaundice, cataracts, poor wt gain, hepatomegaly
No screening in UK
Galactose free diet (milk free), Soy milk
what is MCAD deficiency and how does it present?
Completely ‘normal’ when well
Hypoglycaemia when unwell or fasting
Unable to mobilise fatty acids & ketones when low glucose
Reduced total carnitine, reduced free carnitine/acyl carnitine ratio
how is MCAD deficiency managed?
Avoid fasting (unable to eat)
Slow release carbohydrates eg starch (provide glucose overnight)
Supplement Carnitine
Riboflavin - benefits some patients with electron transport chain deficiency
Medic-Alert Bracelet
what are lysosomes and their function ?
Spherical vesicles containing >50 hydrolytic enzymes
Breaks down all kinds of biomolecules
Phagocytosis, endocytosis, autophagy
Stomach of the cell; Suicide bags or sacs; Recycling unit
what signs and symptoms are seen in lysosomal disorders?
how is it managed?
Coarse facies, mental retardation, short stature, contractures, dysostosis multiplexa
Symptomatic treatment
