Metabolic Flashcards
Which amino acids accumulate in maple syrup urine disease?
Leucine (most toxic)
Isoleucine
Valine
Clinical features of maple syrup urine disease?
Well at birth then symptomatic in first days -weeks of life with
- poor feeding
- vomiting
- lethargy
- loss of Moro reflex
- hypertonia and muscle rigidity (may have intermittent flaccidity), opisthotonus
- maple syrup urine smell
- seizures
What lab investigations would you find in MSUD
- Elevated amino acids (leucine, isoleucine, valine)
- high anion gap metabolic acidosis
+/- hypoglycaemia with ketosis
Clinical features of PKU
- Fair skin and hair
- vomiting
- irritability
- eczematoid rash
- peculiar, “mousy” odour
- can develop low IQ if not detected early
Management of PKU
Dietary restriction of phenylalanine for life (can have a small amount + need SOME tyrosine in diet)
Features of tyrosinemia type 1
Hepatorenal type, present ~2-6months with
- hepatomegaly that progresses to hepatic adenomas -> hepatoblastomas -> liver failure
- failure to thrive
- renal tubular acidosis resembling Fanconi syndrome
- rickets
due to deficiency of fumarylacetoacetate hydroxyls (final step in tyrosine metabolism pathway)
Features of homocystinuria
- Ectopia lentis (downward like the IQ)
- myopia
- iridodenesis
- similar habitus to Marfans syndrome: tall, lean, long limbs, erachnodactyly, pectus excavatum or carinatum, high arched palate, teeth crowding
- increased risk of venous and arterial thromboembolism
Lab findings in methylmalonic acidemia
Presents in first few days of life with:
- Ketotic hypoglycaemia
- Metabolic acidosis
- High ammonia (not as high as urea cycle defects)
- Urine organic acid: elevated methylmalonic acid and abnormal ketones bodies
- May have cytopenias
Presentation of methylmalonic academia
Early onset form (first few days of life)
- Hyperammonemia
- Ketoacidosis and severe metabolic acidosis
- Thrombocytopenia
- Sepsis like picture with feeding problems, vomiting, lethargy, hypotonia
Can present later with FTT, vomiting, chronic ketotic hyperglycinemia
Metabolic condition with high ammonia (>1000)
Urea cycle defect (Eg OTC deficiency)
Causes of hypoketotic hypoglycemia
- Fatty acid oxidation defects (eg MCAD deficiency)
- hyperinsulinemia
Clinical features of VLCAD deficiency
More severe than MCAD deficiency + usually presents earlier with hypoglycaemia with fasting, muscle weakness and muscle pain, rhabdomyolysis. Can have cardiomyopathy associated with fasting
Typically affects heart and skeletal muscles
Features of MCAD deficiency
Usually present first 3mo-5yrs with:
- fasting associated hypoketotic hypoglycemia, lethargy +/- vomiting
- elevated transaminases and CK whilst fasting
- little-no metabolic acidosis
Presentation of X-linked adrenoleukodystrophy
Onset ~4-8yrs with
- hyperactivity
- impaired auditory discrimination and spatial awareness
- seizures
- mild hypopigmentation
- adrenal dysfunction (later)
Examples of x-linked lysosomal storage disease
Fabry disease - usually presents in adolescents/adults with pain crisis, angiokeratomas, reduced sweating
MPS II (Hunter syndrome)
Features of Tay-Sachs
- Initially normal, then regress, then die by 2-5yrs
- Enhanced startle reflex to noise or light
- Progressive loss of motor skills
- Axial hypotonia with extremity hypertonia
- Hyperreflexia
Macular cherry red spot
Features of glycogen storage diseases
Presents ~3-4 months old with:
- Hepatomegaly with ~normal LFTs
- Ketotic Hypoglycemia
- Lactic acidosis, hyperuricemia, hyperlipidemia
- FTT
“doll like facies” with fat cheeks, thin extremities
Management of homocystinuria
Vitamin B6 (pyridoxine)
Diet low in methionine (which gets broken down into homocysteine)
Betaine (converts homocysteine back to methionine)
Cause of galactosemia
Deficiency of enzyme GALT, causing galactose to be metabolised poorly or not at all -> build up in liver, kidneys, brain
E coli sepsis think of which metabolic condition
Galactosemia
Features of Pompe Disease (GSD Type II)
infantile form = severe
- hypertrophic cardiomyopathy (high voltage QRS and shorted PR on ECG)
- hypotonia
- weakness
- macroglossia
- FTT
- hepatomegaly
Juvenile form
- progressive MSK manifestations
Elevated CK, AST, LDH
Coarse facies, midface hypoplasia
CORNEAL CLOUDING
inguinal/ umbi hernia
macrocephaly +/- hydrocephalus
hepatosplenomegaly
early coronary artery disease
Hurler syndrome (MPS 1)
Differences between Hurler syndrome (MPS 1) and Hunter Syndrome (MPS 2)
Hurler syndrome have corneal clouding
Hurler syndrome = AR, Hunter syndrome = XLR
(Hunters will be boys who need their eyesight to hunt)
Features of Zellweger Spectrum Disorder (Peroxisomal disorder)
- Regression
- High forehead, broad nasal bridge, anteverted nares
- Large fontanelle
- Cataracts
- Hearing and Vision loss
- Abnormal LFTs and jaundice
- Calcific stippling of long bones
Most die by age 1
Treatment of hyperammonemia?
Sodium benzoate and sodium phenylbutyrate
or
Dialysis
Onset of lethargy, nausea, vomiting with eating fruit?
Hereditary fructose intolerance
- occurs due to deficiency of aldolase B -> build up of fructose 1 phosphate
- also causes proximal tubule dysfunction and liver damage (hepatomegaly, jaundice, hypoglycemia)
Features of galactosemia
- Presents early (with BF)
- build up of galactose in liver + brain
-> N, V, D, hepatomegaly, jaundice, poor feeding + FTT - > seizures, ID
How many kcal per gram of fat, protein, carbohydrate
9kcal/g of fat
4kcal/g of carbs and protein
Features of Gaucher Disease?
Accumulation of large fatty macrophages in RES
- bone pain
- thrombocytopenia and anaemia
- hepatoSPLENOMEGALY
- Neuronopathic types 2+3 - feeding difficulties, opisthotonus/posturing, macular cherry red spots, early death
What is X-linked adrenoleukodystrophy
Disorder of oxidation of VLCFAs
Results in severe inflammatory demyelination typically of the periventricular deep white matter (posterior predominant)
Group of metabolic disorders that commonly causes a respiratory alkalosis
Urea cycle defects
What would you expect to be abnormal in familial hypercholesterolemia?
Elevated LDL
Elevated total cholesterol
(HDL and triglycerides usually normal)
FH is due to mutations in apolipoprotein B and PCSK9
Features of cystinosis
Fanconi syndrome (proximal tubule)
Poor weight gain
Rickets
Hepatosplenomegaly
Corneal deposits
Fair skin and eyes
Management:
cysteamine
Metabolic causes for rhabdomyolysis
LCHAD and VLFCAD (after long periods of exercise)
GSDs (particularly type V- McArdles) after short periods of exercise
Hepatomegaly, fasting hypoglycaemia, short stature
Think Glycogen storage disorder
Causes of ketotic hypoglycaemia
- GSD 1, 3, 6, 9
- Hereditary fructose intolerance
- Organic academies (eg MMA)
- Ketone utilisation disorders
- Idiopathic
Features of Zellweger spectrum disorder (Peroxisomal Biogenesis Disorder)
Think “hepatocerebrorenal” syndrome
- Heptamegaly, cholestasis, cirrhosis, biliary dysgenesis, and coagulopathy
- GDD, Hypotonia, weakness, absent reflexes, hearing + vision loss
- Cystic kidney disease
- Calcific stippling of bones
- Facial dysmorphism
Clinical features of Menkes Disease (kinky hair syndrome)?
Features of severe copper deficiency:
- Developmental delay and epilepsy in early infancy
- ‘kinky’ wirey hair
- Progressive neurological symptoms
- growth failure
- skin hypopigmentation
- osteoporosis and spur formation
It is X-linked
Key features of Lesch- Nyhan syndrome
- Choreoathetosis or dystonia
- Eventual hypertonia with spasticity and hyperreflexia
- Self mutilating behaviour
Carriers of Gaucher Disease are at increased risk of what?
Parkinsons Disease
Which metabolic condition is associated with a low CSF glucose: blood glucose ratio (<0.6)?
GLUT-1 deficiency
Normal response to hypoglycemia?
Suppressed Insulin (levels should be undetectable)
Production of cortisol, adrenaline, GH, ketones
Metabolic condition in which narcolepsy and cataplexy are common?
Niemann Pick Disease type C (caused by intralysosomal accumulation of cholesterol)
Lab finding in peroxisomal disorders (eg Zellweges spectrum (incl resfum), adrenoleukodystrophy)?
Elevated VLCFAs
What is acid alpha glucosidase?
An enzyme that helps break down glycogen in the lysosome. It is deficient in Pompe disease (GSD II) and this is one of the tests
What disease are urinary glycosaminoglycans elevated?
Mucopolysaccharidoses (eg Hunter, Hurler syndrome)
ABCD1 gene mutation -> peroxisomal disorder with lack of oxidation of very long chain fatty acids -> build up on very long chain fatty acids in CNS and adrenal cortex.
X-linked adrenoleukodystrophy
Management of X-linked adrenoleukodystrophy
Glucocorticoids for adrenal insufficiency
HSCT as soon as mild features of leukodystrophy present
Complete absence of galactose-1-phosphate uridyl transferase (GALT) in red bloods cells suggests which metabolic condition?
Galactosemia
Metabolic disorders that can present with subdural haematoma and retinal haemorrhages?
Type 1 glutaric acidemia
Menkes disease
Deficiency of lysosomal alpha galactosidase in plasma, leukocytes and cultured skin fibroblasts suggests which metabolic condition
Fabry disease
A sphingolipodises that is XLR, presents in adolescence with severe episodic pain in hands and feet triggered by heat exposure or fever
