Chempath 6: Metabolic disorders and screening 2 Flashcards

1
Q

A neonate presents with cataracts, conjugated bilirubinaemia, hepatomegaly after starting milk feeds.

Most likely metabolic disease ?

A

Galactosaemia

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2
Q

A positive Fehling’s and Benedict’s test in the absence of glucose in the urine suggests …………….

A

Glacatosaemia

These tests detect reducing sugars in the urine.

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3
Q

A baby born in Quebec Canada presents with bloody stool, failure to thrive, jaundice, hepatomegaly and a cabbage like odour.

What is the most likely diagnosis ?

A

Tyrosinaemia (type 1)

treated by restricting tyramine in the diet (soft cheese etc)

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4
Q

A neonate presents with signs of a non-infective encephalopathy, failure to thrive and hyperventilation. The consultant suggests that Protein may be the trigger.

Most likely diagnosis ?

A

Urea cycle disorders

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5
Q

list disorders that count as urea cycle defects

A

lysinuric protein intolerance
hyperornithaemia - hyperammonemia - homocitrullinuria
citrullinaemia type II

all result in a high ammonia
all autosomal recessive
high plasma glutamine

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6
Q

how do you treat ornithine cycle disorders

A
remove ammonia (using sodium benzoate or sodium phenyl acetate)
reduce ammonia production (by low protein diet)
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7
Q

list key features of urea cycle disorders

A
vomiting without diarrhoea
respiratory alkalosis 
hyperammonaemia 
neurological encephalopathy 
avoidance or change in diet
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8
Q

causes of hyperammonaemia with metabolic acidosis and a high anion gap

A

organic acidurias
caused by defects within the metabolism of branched chain AA
associated with funny smelling urine (cheesy/ sweaty smell)

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9
Q

presentation of organic acidurias in neonates

A
unusual odour
lethargy 
feeding problems 
truncal hypotonia/ limb hypertonia 
myoclonic jerks 
hyperammonaemia with metabolic acidosis and high anion gap
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10
Q

presentation of chronic intermittent organic acidurias

A

recurrent episodes of ketosis coma
cerebral abnormalities
Reye syndrome: plasma ammonia, plasma/urine AA, urine organic acids, plasma glucose and lactate

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11
Q

list features of mitochondrial fatty acid beta oxidation disorders

A

cause hypoketotic hypoglycaemia
hepatomegaly and cardiomegaly
investigations = blood ketones, urine organic acids, blood spot acylcarnitine profile

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12
Q

features of carbohydrate disorders

A

cannot break down carbs
galactosaemia
glactose-1-phosphate uridyl transferase (Gal-1-PUT) deficiency is most severe and common form
leads to liver and kidney disease

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13
Q

presentation of carbohydrate disorders

A
vomiting
diarrhoea
conjugates hyperbilirubinaemia
hepatomegaly 
hypoglycaemia 
sepsis 
bilateral cataracts 

inv: urine reducing substances (high galactose levels), red cell Gal-1-PUT

tx - avoid galactose

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14
Q

features of glycogen storage disease type 1 (von Gierke disease)

A

phosphatase deficiency
cannot export G6P and G1P after glucose breakdown
become hypoglycaemic

features: hepatomegaly, nephromegaly, hypoglycaemia, lactic acidosis, neutropenia

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15
Q

features of mitochondrial disorders

A

maternally inherited

defective ATP production - multisystem disease esp affecting organs with high energy requirements

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16
Q

investigations in mitochondrial disorders

A

high lactate
CSF lactate/pyruvate
CK
muscle biopsy

17
Q

features of congenital disorders of glycosylation

A

defect of post-translational protein glycosylation

associated with cardiomyopathy, osteopenia, hepatomegaly, sometimes dysmorphic facial features

18
Q

features of paroxysmal disorders

A

metabolism of long chain fatty acids and biosynthesis of complex phospholipids

neonates: muscular hypotonia, seizures, hepatic dysfunction, mental deficiency
infantile: bony changes

19
Q

features of lysosomal storage disorders

A

defects of lysosomal hydrolyses
accumulation of substrates within organelles - organomegaly
dysmorphia, regression
treat: BM transplant, exogenous enzymes

20
Q

describe what’s been included in the Guthrie screening

A
1969 - PKU 
1970 - congenital hypothyroidism 
2004 - CF 
2006 - SCD 
2009 - medium chain acylcoa dehydrogenase deficiency
21
Q

2 key features of PKU

A

phenylalanine hydroxylase deficiency

test phenylalanine levels

22
Q

2 key features of congenital hypothyroidism

A

dysgenesis/agenesis of thyroid gland

test TSH levels

23
Q

2 key features of CF

A

mutations of CFTR - viscous secretions - ductal blockages
test: immune reactive trypsin
if positive - DNA mutation detection

24
Q

2 key features of medium chain acylcoa dehydrogenase deficiency

A

fatty acid oxidation disorder

acylcarnitine levels by tandem mass spectrometry

25
define specificity
probability in % that someone without the disease will correctly test negative
26
define sensitivity
probability in % that someone with the disease will test correctly positive
27
define PPV
probability that someone who tests positive actually has the disease
28
define NPV
probability that someone who tests negative actually doesn't have the disease
29
list group 1 metabolic disorders
accumulation of toxins... organic acidameias - high urea, ketones, met acidosis, treat with low protein diet, acetylcarnitise and harm-filtration, funny smells urea cycle disorders - high ammonia, respiratory alkalosis, vomiting, treat with low protein diet aminoacidopathies inc PKU - high phenylalanine, blue eyes, retardation
30
list group 2 metabolic disorders
reduced energy stores... glycogen storage disorders - hypoglycaemia, lactic acidosis, hepatomegaly, developmental delay, hepatoblastoma, treat with regular CHO galactossaemia - increased Gal-1-phosphate levels causing cataracts, hypoglycaemia, neonatal conjugated jaundice, test urine, treat with low lactose/galactose diet fatty acid oxidation disorders - hypoglycaemia, neonatal conjugated jaundice, low ketones, screen with blood acylcarnitine, test iron organic acids, regular carbs
31
list group 3 metabolic disorders...
large molecule synthesis... peroxisomal disorders - poor feeds, seizures, retinopathy, hepatomegaly, mixed hyperbilirubinaemia glycosylation disorders - measure serum transferring, lead to retardation and nipple retraction
32
list group 4 metabolic disorders...
defects in large molecule metabolism... lysosomal disorders - slow progressing, neuroregression, hepatosplenomegaly, cardiomyopathy, test urine mucopolysaccharides and WBC enzyme levels
33
list group 5 metabolic disorders...
mitochondrial MELAS, Kearns, Sayre POEMS involve CNS, muscle, heart, high lactate and CK, muscle biopsy diagnostic