Metabolic Disorders Screening 2

Question 1

What can go wrong in the urea cycle?

Answer 1

7 defects of urea cycle +Lysinuric protein intolerance

Question 2

What is caused by urea cycle disorders?

Answer 2

Hyperammoniaemia

Question 3

How do urea cycle defects get inherited?

Answer 3

Autosomal recessive except Ornithine transcarbamylase deficiency (OTC) which is X-linked

Question 4

What are the important part of the urea cycle?

Answer 4

Ornithine, citrulline, arginosuccinate, arginine
Urine orotic acid
Glutamine

Question 5

How do you treat urea cycle disorders?

Answer 5

Remove ammonia

Reduce ammonia production

Question 6

What is the incidence of urea cycle disorders?

Answer 6

1 in 30,000

Question 7

What are the flags for urea cycle disorders?

Answer 7

Vomiting without diarrhoea
Resp. alkalosis
Hyperammonaemia
Avoidance
Change in diet
Neurological encephalopathy

Question 8

What causes organic acidurias?

Answer 8

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

Question 9

What does 3OH-isovaleric acid Isovaleryl glycine cause?

Answer 9

Cheesy or sweaty smelling urine

Question 10

How do organic acidurias present in neonates?

Answer 10

Unusual odour
Lethargy
Feeding problems
Truncal hypotonia/ limb hypertonia
Myoclonic jerks
Metabolic acidosis with large anion gap
Hypocalcaemia

Question 11

How do chronic intermittent forms of organic acidurias present?

Answer 11

Recurrent episodes of ketoacidotic coma, cerebral abnormalities, Reye syndrome

Question 12

What are the symptoms of Reye syndrome?

Answer 12

Vomiting, lethargy, increasing confusion, seizures, decerebration, respiratory arrest
Triggered by: e.g. salicylates, antiemetics, valproate

Question 13

What does glycogen storage disease type 1 pressent with?

Answer 13

Hepatomegaly
Nephromegaly
Hypoglycaemia
Lactic Acidosis
Neutropenia

Question 14

What are mitochondrial disorders?

Answer 14

Defective ATP production leads to multisystem disease especially affecting organs with a high energy requirement such as brain, muscle, kidney, retina and endocrine organs.

Question 15

When do mitochondrial disorders present?

Answer 15

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)

Question 16

What are the lab findings in mitochondrial disorders?

Answer 16

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)

Question 17

What does congenital disorders of glycosylation cause?

Answer 17

Defect of post-translational protein glycosylation.

Multisystem disorders associated with cardiomyopathy, osteopenia, hepatomegaly and (in some cases) dysmorphia facial or otherwise

Question 18

What does CDG type 1a cause?

Answer 18

abnormal subcutaneous adipose tissue distribution with fat pads and nipple retraction.

Question 19

What is the mortality of congenital disorders of glycosylation?

Answer 19

Mortality 20% in first year.

Question 20

What are the lab findings of CDG?

Answer 20

Transferrin glycoforms (serum)

Question 21

What are peroxisonal disorders?

Answer 21

Metabolism of very long chain fatty acids and biosynthesis of complex phospholipids

Question 22

What is the neonatal profile of peroxisomal disorders?

Answer 22

Severe muscular hypotonia

Seizures, hepatic dysfunction
including mixed hyperbilirubinaemia
and dysmorphic signs

Question 23

What is the infant profile of peroxisomal disorders?

Answer 23

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.

Question 24

What would you find in the lab for peroxisomal disorders?

Answer 24

Very long chain fatty acid profile

Question 25

What is lysosomal storage disease?

Answer 25

Intraorganelle substrate accumulation leading to organomagaly (connective tissue, solid organs, cartilage, bone and nervous tissue) with consequent dysmorphia

Regression

Question 26

What do you see in the lab in LSD?

Answer 26

Urine mucopolysaccharides and/or oligosaccharides

Leucocyte enzyme activities

Question 27

What is the treatment of LSD?

Answer 27

Bone marrow transplant

Exogenous enzyme