metabolic disorders 2 Flashcards
which Inherited metabolic disorders typocally present like:
Cerebral oedema, seizures, comatose
Disorders of the urea cycle leading to :
Hyperammonaemia
disorders include:
○ Lysinuric protein intolerance
○ Hyperornithinaemia-Hyperammonemia-Homocitrullinuria (HHH)
○ Citrullinaemia type II
○ Ornithine transcarbamylase deficiency (OTC)
how are the disorders of the urea cycle inherited?
Autosomal recessive
except ○Ornithine transcarbamylase deficiency (OTC) -> X linked inheritance
what will ivx show in testing for disorders of urea cycle?
amino acids - high or absent
urine orotic acid
rx:
remove ammonia - give sodium benzoate or phenylacetate or dialysis
reduce ammonia production
urea cycle disorders present how?
Long term psychiatric disorders - eg ADHD
avoidance of protein, subsequent illness around family celebrations eg Christmas
confusion, disorientation, nausea, vomintg etc
○ Vomiting without diarrhoea ○ Respiratory alkalosis ○ Hyperammonaemia ○ Neurological encephalopathy ○ Avoidance or change in diet
Hyperammonaemia with Metabolic ACIDOSIS and High Anion Gap is associated with?
organic acidurias ->
The most important involve the defects within the complex metabolism of the branched chain amino acids (leucine, isoleucine and valine)
isovaleric academia (organic acidurias) present how? and why?
- Unusual odour or funny smelling urine due to:
3OH-isovaleric acid - cheesy/sweaty smell
isovaleryl glycine - lethargy, feeding problems
- truncal hypotonia
- limb hypertonia
- myoclonic jerks
ivx findings;
hypocalcaemia, neutropaenia, thrombocytopaenia, pancytopaenia
§ Hyperammonaemia with a metabolic acidosis and a high anion gap (not lactate)
name a Chronic Intermittent Form of organic aciduria, how it presents and its triggers?
REYE SYNDROME
□ Vomiting □ Lethargy □ Increased confusion □ Seizures □ Decerebration □ Respiratory arrest
□ Triggered by: salicylates (aspirin), anti-emetics, valproate
why is aspirin/salicylate not given to children anymore?
triggers reye’s syndrome
what do we screen for in reye’s syndrome?
○ Plasma ammonia ○ Plasma/urine amino acid ○ Urine organic acids ○ Plasma glucose and lactate ○ Blood spot carnitine profile (stays abnormal in remission)
○ NOTE: the top 4 should be collected during the acute episode because the abnormal metabolites will disappear after a few days
you note hypoketotic hypoglycaemia (+ hepatomegaly and cardiomyopathy). what are you thinking?
Mitochondrial Fatty Acid Beta-Oxidation Defects
how do we investigate Mitochondrial Fatty Acid Beta-Oxidation Defects?
○ Blood ketones
○ Urine organic acids
○ Blood spot acylcarnitine profile
§ Conjugated hyperbilirubinaemia is always ___?
pathological
list the types of Galactosaemia. what is galactosaemia?
disorders of carbohydrate breakdown
Galactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency
how do Galactosaemias present?
§ Vomiting
§ Diarrhoea
§ Hepatomegaly
§ Hypoglycaemia
very important:
§ Conjugated hyperbilirubinaemia
§ Sepsis (because galactose-1-phosphate inhibits immune responses)
-> bilateral catarcts - due to aldolase in eyes lenses
ivx for galactosaemia’s?
treatment?
§ Urine reducing substances (high levels of galactose)
§ Red cell Gal-1-PUT
treatment:
§ Avoid galactose (e.g. milk)
which condition presents as and why:
§ Hepatomegaly
§ Nephromegaly
§ Hypoglycaemia !!
§ Lactic acidosis !!
Neutropaenia
• Glycogen Storage Disease Type I (von Gierke disease) -
most severe
reason:
there is a huge build of glycogen which muscles cant make use of because
Glucose 1 phosphatase deficiency means breakdown products of glucose cant be removed/exported from cell
list 3 mitochondrial disorders by age group?
neonates - Barth: affects heart, low neutrophils
5-15: MELAS - mitochondrial encephalopathy, lactic acids and stroke-like episodes
12-30: Kearns-sayre: deafness, affects eyes
ivx for mitochondrial disorders?
Elevated lactate (alanine) – after periods of fasting (e.g. overnight), before and after meals
(CSF lactate / pyruvate – deproteinised at bedside)
CSF protein (raised in Kearns-Sayre syndrome)
Mitochondrial DNA analysis (not so useful in children)
what is the main issue in mitochondrial disorders?
defective ATP production
affects a whole range of systems
name a Congenital disorder of glycosylation?
how does it present?
CDG type 1a
abnormal subcutaneous adipose tissue distribution with fat pads and nipple retraction.
how are Congenital disorder of glycosylation investigated for?
Lab: Transferrin glycoforms (serum)
which is true Congenital disorder of glycosylation are:
Defect of post-translational protein glycosylation.
Defect of pre-translational protein glycosylation.
Defect of post-translational protein glycosylation.
disorders of metabolism of very long chain fatty acids and biosynthesis of complex phospholipids
are called? how do they present?
ivx?
Peroxisomal disorders
neonate: Severe muscular hypotonia.
infant: many signs including bony changes; fotanel doesnt close till 1y/o, osteopaenia of long bones
ivx - Very long chain fatty acid profile
how do Lysosomal storage diseases present?
Intraorganelle substrate accumulation leading to organomagaly with consequent dysmorphia.
what is the ivx for Lysosomal storage diseases?
Urine mucopolysaccharides and/or oligosaccharides
Leucocyte enzyme activities
what is the treatment for Lysosomal storage diseases?
Bone marrow transplant
Exogenous enzyme
