Metabolic Flashcards
- What are the causes of homocystinuria?
2. What are the clinical manifestations?
Homocystene is the metabolite of methionine (essential AA)
- Causes: enzyme deficiency (inherited), B12/B6/ folate deficiency (acquired)
- Atherosclerosis, TIA, clots, deformed bones, ectopia lentis, developmental delay/regression
What is phenylkeyonuria (PKU)?
- Cause?
- Genetics?
- Clinical sx?
- Management?
PKU
- Caused by phenylalanine hydroxylase deficiency leading to a build up of phenylalanine (enzyme metabolises phenylalanine to tyrosine in liver)
- Genetics- autosomal recessive, multiple mutations in chromosome 12q24
- Clincal: demyelination- cognitive impairment, seizures, gait abnormality, osteopaenia, light hair and eyes, visual disturbance, musty odour
- Lifelong dietary restriction
What is maple syrup urine disease?
- Cause?
- Genetics?
- Clinical?
- Management?
- MSUD is where you cannot break down branched chain amino acids (valene, leucine, isoleucine) leading to branched chain ketoaciduria. Caused by BCKAD enzyme deficiency (kreb cycle for gluconeogenesis)
- Autosomal recessive
- Clinical: sweet smelling urine, encephalopathy, cerebral oedema (imcreased Na and H20 into cells), seizures, coma, poor feeding
- Mx- restrict branched chain AA.
Liver transplant (restore normal levels of BCKAD)
What does MCAD stand for?
What kind of metabolic disorder?
Clinical presentation?
MCAD = medium chain acyl CoA reductase deficiency- needed for oxidation of med chain FA to acetyl CoA for ketogenesis
Fatty acid oxidation defect
Clinical: hypoketotic hypoglycaemia, lethargy, encephalopathy
- What is the most common urea cycle disorder?
- Genetics?
- Clinical presentation?
- Management?
- OTC deficiency- enzyme in urea cycle. Causes ammonia build up as cannot be metabolised
- X linked
- Presents w protein aversion, recurrent vomiting, encephalopathy, derranged LFTs and coags
- Low protein diet, sodium benzoate (increase disposal of metabolites), liver transplant
What are two examples of mitochondrial disorders?
Presentation?
Mitochondrial disorder examples:
1. Kearns Sayre syndrome
2. Cytochrome C oxidase def
Causes insufficient ATP production
Presents with metabolic acidosis, lactic acidosis, hypoglycaemia , liver dysfunction
Glycogen storage disase type 1
- Subtypes and cause?
- Presentation?
- Mx?
- Type 1a aka von gierke disease caused by G6P deficiency.
Type 1b due to transport defect of G6P - Severe hypoglycaemia after brief fast with lactic acidosis and ketoacidosis. Hepatomegaly, growth retardation, delayed puberty, renal disease
- High cornstarch diet
- What is MPS type 1?
- Severity scale subtypes?
- Physical features?
- MPS type 1 is complete or partial deficiency in a-L-iduronidase, an enzyme that breaks down dermatin and heparin
- Hurler/hurler scheie/ scheie (most to least severe)
- Coarse facies, frontal bossing, corneal clouding/blindness, fat cheeks, depressed nasal bridge, cardiomyopathy, growth failure, developmental delay/regression, hepatosplenomegaly, herniae , stiff joints and contractures
What is MPS type 2?
Hunter syndrome= MPS 2
X linked
Like hurler syndrome but without corneal clouding
Also has pebbled skin appearance
Gaucher disease
- Cause?
- Presentation?
- Deficiency in glucocerebrocidase which accumulates in lysosomes of macrophages. Mutation in GBA gene
- Anaemia/fatigue, decreased bone density, thrombocytopaenia
Nieman pick disease
- Cause?
- Presentation?
- Deficiency of sphingomyelinase due to mutation on SMPDI gene
- Present with jaundice, hepatosplenomegaly, feeding difficulties, loss of tone and reflexes, cherry red spots in macula, interstitial lung disease. More common in ashkenazi Jews
Tay sachs disease
- Cause?
- Presentation?
- Caused by HEX -A mutation on chromosome 15 causing HEX A accumulation
- Progressive CNS symptoms, cherry red spots in macula
Fabry disease
- Cause?
- Presentation?
- Caused by GLA gene mutation affecting a-GAL-A enzyme
- Tingling neuropathic pain triggered by exercise, angiokeratomas in lowe abdo, decrease sweating, kidney disease, arrythmia
