IEM Flashcards

1
Q

What is alkaptonuria?

A
  • Autosomal recessive condition
  • Urine turns black on standing and alkalinisation
  • Black ochrontic pigmentation of cartilage and collagenous tissue
  • Arthritis
  • Homogentisic acid oxidase deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is cystinuria?

A
  • 1:7000
  • defective transport of cysteine and dibasic AAs through epithelial cells of renal tubule and intestinal tract
  • Cysteine has low solubility - formation of calculi in renal tract
  • Mutations in SLC3A1 AA transporter gene (Chr2p) and SLC7A9 (Chr 19)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the cause of albinism?

A

Tyrosinase negative

  • Type 1a - complete lack of enzyme activity due to production of inactive tyrosinase
  • Type 1b - reduced activity of tyrosinase

Tyrosinase positive

  • Type II - AR, biosynthesis of melanin reduced in skin, hair and eyes
  • most individuals do acquire a small amount of pigment with age
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is pentosuria?

A
  • Pentose in urine
  • Excrete 1-4g pentose sugar daily
  • Benign
  • Almost exclusively Ashkenazi jews of Polish-Russian extraction (1:2500 births)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the one gene- one enzyme concept?

A
  • All biochemical processes in all organisms are under genetic control
  • These processes are resolvable into a series of stepwise reactions
  • Each biochemical reaction is under the ultimate control of a different single gene
  • Mutation of a single gene results in an alteration in the ability of the cell to carry out a single primary chemical reaction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the different mechanisms of inheritance?

A
  • AR - both parents carry a mutation affecting the same gene; 1/4 risk; consaguinity increases risk; e.g. CF and sickle cell
  • AD - rare in IEMs, e.g. Huntingdons, Marfans
  • X-linked - females passing on condition to their affected sons; no male to male; female carriers can have random inactivation of one of the X chromosomes, leading to manifestation
  • Codominant - two different alleles of a gene are expressed, each makes a slightly different protein; both alleles influence genetic trait; e.g. ABO
  • Mitochondrial inheritence - inherit mtDNA from mother; only females can pass on
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the frequency of IEMs?

A
  • Individually rare, but collectively present a sizeable problem
  • Account for approx 42% of deaths within 1st year of life
  • Make a significant contribution to the 1% of children at school with physical handicap, and the 0.3% with severe learning difficulties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

When do the IEMs present?

A

Neonatal

  • Maple syrup urine disease
  • Tyrosinaemia
  • OTC (urea cycle defect)

Adult

  • Wilson’s
  • Haemochromatosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the defects that cause neonatal presentation?

A
  • AA metabolism
  • Organic acid metabolism
  • Carbohydrate metabolism
  • Urea cycle defects
  • Respiratory chain defects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do we do newborn blood spot screening?

A
  • Samples should be taken on day 5

- All four circles on card need to be completely filled with a single drop of blood which soaks through

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the clues in neonates for IEM?

A
  • Consanguinity
  • Family history of similar illness in sibs or unexplained deaths
  • Infant who was well at birth, but starts to deteriorate for no obvious reason
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the classic presentation?

A
  • Full term pregnancy
  • Non-specific symptoms - poor feeding, lethargy, vomiting, hypotonia, fits
  • Specific - abnormal smell (sweet, must, cabbage-like); cataracts, hyperventilation secondary after metabolic acidosis, neurological dysfunction with respiratory alkalosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the first line lab investigations?

A
  • Blood gas analysis
  • Blood glucose
  • Plasma ammnia
  • LFTs
  • Urinary ketones and reducing substances
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the second line investigations?

A
  • Plasma and urine AAs
  • Urinary organic acids and orotic aid
  • Blood acyl carnitines, lactate and pyruvate
  • Urinary glycosaminoglycans
  • Plasma very long chain FAs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the confirmatory investigations?

A
  • Enzymology - red cell galactose-1-phosphate uridyl transferase and lysosomal enzyme screening
  • Muscle/liver biopsy
  • Fibroblast studies
  • Complementation studies
  • Mutation analysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the possible metabolic causes for acute liver disease in a neonate?

A
  • Classical galactosaemia
  • Hereditary fructose intolerance
  • An organic acidaemia
  • Tyrosinaemia type 1