Metabolic Disorders Screening 2 Flashcards
What can go wrong in the urea cycle?
7 defects of urea cycle +Lysinuric protein intolerance
What is caused by urea cycle disorders?
Hyperammoniaemia
How do urea cycle defects get inherited?
Autosomal recessive except Ornithine transcarbamylase deficiency (OTC) which is X-linked
What are the important part of the urea cycle?
Ornithine, citrulline, arginosuccinate, arginine
Urine orotic acid
Glutamine
How do you treat urea cycle disorders?
Remove ammonia
Reduce ammonia production
What is the incidence of urea cycle disorders?
1 in 30,000
What are the flags for urea cycle disorders?
Vomiting without diarrhoea Resp. alkalosis Hyperammonaemia Avoidance Change in diet Neurological encephalopathy
What causes organic acidurias?
The most important involve the complex metabolism of the branched chain amino acids (leucine, isoleucine and valine) for example:
Export from cell as: Isovaleryl carnitine Excrete as: 3OH-isovaleric acid Isovaleryl glycine
What does 3OH-isovaleric acid Isovaleryl glycine cause?
Cheesy or sweaty smelling urine
How do organic acidurias present in neonates?
Unusual odour Lethargy Feeding problems Truncal hypotonia/ limb hypertonia Myoclonic jerks Metabolic acidosis with large anion gap Hypocalcaemia
How do chronic intermittent forms of organic acidurias present?
Recurrent episodes of ketoacidotic coma, cerebral abnormalities, Reye syndrome
What are the symptoms of Reye syndrome?
Vomiting, lethargy, increasing confusion, seizures, decerebration, respiratory arrest
Triggered by: e.g. salicylates, antiemetics, valproate
What does glycogen storage disease type 1 pressent with?
Hepatomegaly Nephromegaly Hypoglycaemia Lactic Acidosis Neutropenia
What are mitochondrial disorders?
Defective ATP production leads to multisystem disease especially affecting organs with a high energy requirement such as brain, muscle, kidney, retina and endocrine organs.
When do mitochondrial disorders present?
Age Disorder: Birth Barth (cardiomyopathy, neutropenia, myopathy)
5-15 MELAS (mitochondrial encephalopathy, lactic acids and stroke-like episodes)
12-30 Kearns-Sayre (Chronic progressive external ophthalmoplegia, retinopathy, deafness, ataxia)
What are the lab findings in 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)
CK
Muscle biopsy
Mitochondrial DNA analysis (not so useful in children)
What does congenital disorders of glycosylation cause?
Defect of post-translational protein glycosylation.
Multisystem disorders associated with cardiomyopathy, osteopenia, hepatomegaly and (in some cases) dysmorphia facial or otherwise
What does CDG type 1a cause?
abnormal subcutaneous adipose tissue distribution with fat pads and nipple retraction.
What is the mortality of congenital disorders of glycosylation?
Mortality 20% in first year.
What are the lab findings of CDG?
Transferrin glycoforms (serum)
What are peroxisonal disorders?
Metabolism of very long chain fatty acids and biosynthesis of complex phospholipids
What is the neonatal profile of peroxisomal disorders?
Severe muscular hypotonia
Seizures, hepatic dysfunction
including mixed hyperbilirubinaemia
and dysmorphic signs
What is the infant profile of peroxisomal disorders?
retinopathy often leading to early blindness, sensorineural deafness, hepatic dysfunction, mental deficiency, ftt, dysmorphic signs.
Bony changes involve a large
fontanel which only closes
after the first birthday,
osteopenia of long bones,
and often calcified stippling
especially the patellar region.What would you find in the lab for peroxisomal disorders?
Very long chain fatty acid profile
What is lysosomal storage disease?
Intraorganelle substrate accumulation leading to organomagaly (connective tissue, solid organs, cartilage, bone and nervous tissue) with consequent dysmorphia
Regression
What do you see in the lab in LSD?
Urine mucopolysaccharides and/or oligosaccharides
Leucocyte enzyme activities
What is the treatment of LSD?
Bone marrow transplant
Exogenous enzyme
