Inborn errors of metabolism Flashcards
Inborn errors screened for using Guthrie test
PKU MCADD MSUD IVA GA1 HCU
Types of inborn error that present in the neonate
Organic acid or urea cycle disorders
Vomiting, encephalopathy, acidosis, coma, death
Types of inborn error that present in childhood
MCADD
Hypoglycaemia, vomiting, encephalopathy, acidosis, coma, death
Subacute inborn errors
Lysosomal disorders
Organomegaly, regression, coarse facies
Signs there may be an inborn error of metabolism
Encephalopathy + ketones + acidosis
Anion gap >25mmol/L
PKU
- Enzyme involved
- Presentation
- Treatment
Phenylalanine hydroxylase
6-12 months, developmental delay, eczema, seizures, musty smell, blue eyes, fair hair
Diet restriction of phenylalanine (found in eggs, meat, milk, aspartame)
HCU (Homocysteinuria)
- Enzyme involved
- Presentation
- Treatment
Cystathionine synthetase deficiency
Developmental delay, ectopia lentis (subluxation), psychiatric disorders, convulsions, marfanoid, fair complexion, brittle hair, VTE risk
Pyridoxine, low methionine diet
Tyrosinaemia
- Enzyme involved
- Presentation
- Treatment
Fumarylacetoacetase
Liver failure, Fanconi syndrome (proteinuria, glycosuria, hyperchloraemic, hypokalaemic acidosis, ricketts, water loss)
Mx: NTBC
Galactosaemia
- Enzyme involved
- Presentation
- Treatment
Galactose-1-phosphate uridyltransferase
Following lactose containing milk feeds (breast or formula), baby feeds poorly, vomits, jaundice, hepatomegaly and liver failure. Later: chronic liver disease, cataracts, developmental delay
Avoid lactose and galactose
Type 1 Glycogen Storage Disorder
- Enzyme involved
- Presentation
- Treatment
Von Gierke: glucose-6-phosphatase
Onset as infant, enlarged liver and kidneys, growth failure, hypoglycaemia, good prognosis. No muscle involvement.
Maintain blood glucose by frequent feeds or by carbohydrate infusion via a gastrostomy or nasogastric tube in infancy. In older children, glucose levels can be maintained using slow-release oligosaccharides (corn starch).
Type 2 Glycogen Storage Disorder
- Enzyme involved
- Presentation
- Treatment
Pompe: Lysosomal α-glucosidase
Starts as infant. Hypotonia and cardiomegaly at several months. Some liver involvement. Death from heart failure.
As type 1 but can give myozyme (enzyme replacement therapy)
Type 3 Glycogen Storage Disorder
- Enzyme involved
- Presentation
- Treatment
Cori: Amylo-1,6-glucosidase
Starts as infant. Milder features of type I, but muscles may be affected. Good prognosis.
As type 1 but high-protein diet is recommended to prevent growth retardation and myopathy.
Type 5 Glycogen Storage Disorder
- Enzyme involved
- Presentation
- Treatment
McArdle: Phosphorylase
Starts in childhood. No liver pathology. Temporary weakness and cramps muscles after exercise. Myoglobinuria in later life
As type 1
Red flags for urea cycle disorders
Vomiting without diarrhoea
Respiratory alkalosis, hyperammonaemia
Neurological encephalopathy
Urea avoidance
Tend to be autosomal recessive except for OTC which is X-linked
IVA
Cheesy/sweaty smell
Lethargy, feeding problems, truncal hypotonia and limb hypertonia, myoclonic jerks
Hyperammonia, metabolic acidosis, high anion gap
Hypocalcaemia, neutropenia, thrombocytopenia, pancytopenia
