Metabolism and Metabolic Medicine Flashcards
What is the mode of inheritance for most IEMs?
AR
In what IEMs would amino acid and acylcarnitines be useful in?
Urea cycle disorders
Organic acidaemia or amino acidopathy
In what IEMs would urine amino acids be useful in?
Tubulopathy
Cystinosis
In what IEMs would ammonia be useful in?
Urea cycle disorders
In what IEMs would lactate be useful in?
Mitochondrial disorders
Glycogen storage disorders
In what IEMs would Gal-1-PUT assay be useful in?
Galactosaemia
What IEMs are included in the newborn blood spot testing?
PKU
MCAD
GA1 (Glutaric aciduria type 1)
Isovaleric acidaemia
Homocystinuria
Maple syrup urine disease
In what IEMs would very long chain fatty acids be useful in?
Peroxisomal disorder
In what IEMs would urine glycosaminoglycans and oligosaccharides be useful in?
Mucopolysaccharidoses
Oligosaccharidoses
When thinking about IEMs when would white cell enzymes be useful in?
Dysmorphism
Organomegaly
LDs
Developmental regression
What is the dietary treatment for GLUT1 deficiency?
Ketogenic diet
In what IEMs would urine organic acids be useful in?
Organic acidaemia
Fatty acid oxidation disorders
What is the carrier prevalence of PKU?
1 in 50
What is the prevalence of MCAD?
1 in 10000
How does PKU present?
LDs
Seizures
Microcephaly
How is PKU treated?
Phenylalanine restricted diet
How is MCAD treated?
Avoidance of fasting
Emergency regimen for period of illness/stress
What is the prevalence of glutaric aciduria type 1 (GA1)?
1 in 30000-40000
What is the prevalence of PKU?
1 in 10000
How does MCAD present?
Encephalopathy - often rapidly progressive
Collapse after prolonged fasting resulting in a non-ketotic hypoglycaemia
Death if untreated
How does GA1 present?
Macrocephaly with encephalopathic crisis
Usually at 6-18months
Results in dystonic-dyskinetic movement disorder
What is the prevalence of isovaleric acidaemia?
1 in 250000
How is isovaleric acidaemia treated?
Low protein diet
Carnitine
Glycine
How is GA1 treated?
Specialist diet
Avoidance of fasting
Daily carnitine
How does isovaleric acidaemia present?
Metabolic acidosis +/- hyperammonaemia
What is the prevalence of homocystinuria?
1 in 200000-335000
1 in 65000 in those with Irish ancestry
How does homocystinuria present?
Marfanoid appearance
LDs
Lens dislocation
Osteoporosis
Thromboembolism
How is homocystinuria treated?
Low protein diet
Pyridoxine
Folic acid
What is the prevalence of maple syrup urine disease?
1 in 185000
How does maple syrup urine disease present?
Progressive encephalopathy in first week of life
How is maple syrup urine disease treated?
Low protein diet
What is the primary disturbance in respiratory acidosis?
Raised PCO2
What are the effects on the blood gas due to respiratory acidosis?
Low pH
Raised PCO2
-ve BE
What is the bodies compensatory response to respiratory acidosis?
Raised bicarbonate
What are the effects on the blood gas in metabolic acidosis?
Low pH
pCO2 normal or low
BE -ve
What is the primary disturbance in metabolic acidosis?
Low bicarbonate
What is the bodies compensatory response in metabolic acidosis?
Lowers PCO2
What are the effects on the blood gas in respiratory alkalosis?
High pH
PCO2 low
BE +ve
What is the primary disturbance in respiratory alkalosis?
Lowered PCO2
What is the bodies compensatory response in respiratory alkalosis?
Low bicarbonate
What is the primary disturbance in metabolic alkalosis?
High bicarbonate
What are the effects on the blood gas in metabolic alkalosis?
High pH
PCO2 normal or high
BE +ve
What is the bodies compensatory response in metabolic alkalosis?
Raised PCO2
When does acidosis more likely indicate an IEM rather than an acute other illness?
Severe acidosis more proportionate to the usual clinical condition
Abnormalities persist despite standard management
Raised anion gap
How is the anion gap calculated?
(Na+ + K+) - (Cl- + HCO3 -)
What is the normal value for the anion gap in children?
10-16mmol/L
What conditions cause hyperammonaemia?
Severe illness
Liver disease
Certain medications
Transiently in the neonates
What conditions can cause a metabolic acidosis with a raised anion gap?
DKA
Renal failure
Poisoning - salicylate, ethanol, methanol, paraldehyde
IEMs
What is the management of metabolic acidosis?
Treatment of underlying condition
Sodium bicarbonate in severe cases
What conditions cause a metabolic acidosis with a normal anion gap?
Intestinal loss of base - diarrhoea
Renal loss of base - renal tubular acidosis T1+T2
How is hyperammonaemia managed?
Stop any feeds
10% dextrose
Ammonia scavenging medications
Arginine to support urea cycle
PICU for haemofiltration
What are examples of ammonia scavenging medications?
Glycerol phenylbutyrate
Sodium phenylbutyrate
What is it essential to supplement in the diet of a child with PKU?
Tyrosine
What is Barth syndrome?
X-linked disorder affecting cardiolipin metabolism
What features suggest a diagnosis of Barth syndrome?
Male sex
Dilated cardiomyopathy
Neutropenia
Poor feeding and faltering growth
What is the management of Barth syndrome?
Nutritional and immune support
What is the typical blood pattern in Vitamin-D dependent rickets type I?
Low calcium
High PTH
Normal Vit D
Low 1,25-dihydroxycholecalciferol
What causes Vitamin-D dependent rickets type I?
1a-hydroxylase deficiency - meaning kidneys are unable to convert vitamin D to 1,25-dihydroxycholecalciferol
Which enzyme is essential for transporting fatty acids from adipose tissue to mitochondria?
Carnitine acyltransferase I
How does Refsum’s disease present?
Nocturnal visual loss
Anosmia
Retinitis pigmentosa
Progresses to cerebellar disease, neuropathy and cardiomyopathy
What is Refsum’s disease?
Fatty-acid-oxidation defect where phytanic acid is increased in the serum
What genetic mutation is associated with Refsum’s disease?
PHYH gene mutations
In urea cycle disorders what is the typical blood abnormalities which are generally present in all?
Very high ammonia
High glutamine
High alanine
Low/High arginine - depending on defect
What is the most specific test for galactosaemia?
Reduced or absent galactose-1-phosphate uridyltransferase enzyme
What does MELAS stand for?
Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes
when does galactosaemia typically first present?
End of first week of life
How does galactosaemia typically present?
Jaundice with liver function deterioration
Sepsis common (predisposition for e.coli)
Sick infant with raised ammonia
How is galactosaemia treated?
Lactose and galactose-free diet
What most commonly causes MELAS?
Defects in mitochondrial transfer RNA molecules
What is non-ketotic hyperglycinaemia?
Inherited metabolic disorder where patients cannot break down glycine
What is the typical history of non-ketotic hyperglycinaemia?
Apnoea
Seizures in utero
Hiccups
What is the management of non-ketotic hyperglycinaemia?
Sodium benzoate to lover plasma glycine
Dextromethorphan to block glycine’s central action
What is Gaucher’s disease?
Rare, inherited disorder with decreased levels of glucocerebrosidase
What happens to children with fatty acid oxidation defects during fasting or illness?
Hypoketotic hypoglycaemia
What are the carnitine levels like in a patient with a fatty acid oxidation defect?
Free total free carnitine
Abnormal plasma acylcarnitine profile
How does Gaucher’s disease present?
Displacement of healthy cells in bone marrow
Hepatosplenomegaly
Organ dysfunction
Skeletal deterioration
What is the treatment for fatty acid oxidation defects?
Avoid fasting
Restrict fat
Encourage carbohydrate supplementation
Which enzyme are children deficient in with PKU?
Phenylalanine hydroxylase
What plasma level is elevated in Gaucher’s disease?
Acid phosphidase
What is the blood profile in Vitamin-D resistant rickets (aka X-linked hypophosphataemic rickets)?
Low phosphate
Normal calcium
Normal/low vitamin D
What causes vitamin-D resistant rickets?
Renal phosphate wasting secondary to a renal tubular defect in phosphate transport and likely impaired intestinal absorption of calcium
What does NARP stand for?
Neuropathy, ataxia and retinitis pigmentosa
What are the symptoms of GLUT1 deficiency syndrome?
DD
Seizures which are difficult to control
Low CSF glucose (usually <2.2)
Hoes does NARP present?
Sensory neuropathy and ataxia +/- LDs, seizures and cardiac conduction defects
What is dysfunctional in NARP?
ATP synthase
What fluid should be given for maintenance in a child with a fatty oxidation metabolism disorder?
10% dextrose - unless personalised plan known
How does molybdenum cofactor deficiency typically present?
Neurodegenerative condition - presents with early-onset refractory seizures
How is molybdenum cofactor deficiency diagnosed?
Positive sulphites on urine dipstick
Urinary xanthine may be high
Confirmed by further urinary purine studies
What causes OTC deficiency?
Inability to form citrulline from ornithine and carbamoyl - leads to increased serum and urine conc. of orotic acid
What is the most common urea cycle disorder?
Ornithine transcarbamylase (OTC) deficiency
Which lipid does apolipoprotein CII deficiency typically cause elevated levels of?
Triglycerides
How is molybdenum cofactor deficiency inherited?
AR
What is the treatment for biotinidase deficiency?
Oral biotin supplementation
How does biotinidase deficiency present?
Progressive neurological symptoms (hearing and vision)
Rash +/- hair loss
What is tyronsinaemia?
AR disorder leading to progressive liver failure, neurological disease and renal tubular acidosis
What is positive in the urine in classical tyrosinaemia?
Succinylacetone
What are the characteristic features of mucopolysaccharidoses type IV?
Short stubby fingers
Short stature
Corneal opacities
Dysostosis multiplex with hypoplasia of odontoid process
Hypermobility
Cardiac valve abnormalities
What are the typical features of homocystinuria?
Marfanoid habitus
Intellectual disability
Thromboembolism
Ectopia lentis
How is homocystinuria inherited?
AR
What level is raised on newborn blood spot test in MSUD?
Leucine
How does Kearns-Sayre syndrome present?
Progressive ophthalmoplegia
Ptosis
Cardiac conduction abnormalities
What is typically raised in the CSF in Kearns-Sayre syndrome?
Lactate
What is deficient in citrullinaemia?
Arginosuccinate synthetase
What is Leber’s hereditary optic neuropathy?
Mitochondrial disorder which presents in late childhood to early adulthood with unilateral or bilateral progressive visual loss
