Metabolic Flashcards
Toxic molecule disorder meds
Benzoate and phenylbutyrate
Treatment hurler disease (MPS1)
Laronidase
Stem cells
MPS1 (hurler) vs 2 (hunter) vs 3 (San sanfilipo)
Hunter is x linked (boys) and no Corneal clouding (cf 1)
3 no course features and no HSM with heparan sulphate only in urine
Infantile spasms (movement disorder) and regression Typical MRI (loss myelination)
Think Leigh disease
Red flags for metabolic disease
Multi system especially neurological
Episodic
Triggered by foods, illness, exercise
FHx
Lesch-Nyhan is
Juvenile gout
Pantothenate kinase-associated neurodegeneration (PKAN)
Brain iron accumulation
Mucopolysaccharidoses
Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes
What is glycolysis
Break down of glucose to pyruvate
High anion gap acidosis
Organic acidaemia
Ammonia and urea cycle defects
Toxic to brain and causes respiratory centre in brain causes hyperventilation and respiratory alkalosis
Recurrent hypoglycemia associated with intercurrent illness in the absence of
metabolic acidosis or other electrolyte imbalances is suggestive of…
Severe untreated can cause..
Recurrent hypoglycemia associated with intercurrent illness in the absence of
metabolic acidosis or other electrolyte imbalances is suggestive of carnitine
deficiency.
Untreated carnitine deficiency can result in irreversible cardiomyopathy and
skeletal muscle dysfunction.
Vomiting lethargy and hypoglycaemia with fasting could be..
MCAD
Bone, lung, HSM (big spleen) in which disorder
Variable neuro depending on type
Gaucher
Type I: impaired olfaction and cognition
Type II: serious convulsions, hypertonia, mental retardation, and apnea
Type III: muscle twitches known as myoclonus, convulsions, dementia, and ocular muscle apraxia
Presents with FTT, fatty stools and on exam Acanthocytosis blood film, Retinitis pigmentosa, Hypocholesterolemia/low blood cholesterol in which syndrome
Abetalipoproteinemia
REtinitis pigmentosa combined with ophthalmoplegia, dysphagia, ataxia, and cardiac conduction defects is seen in ??
A mitochondrial DNA disorder Kearns-Sayre syndrome (also known as Ragged Red Fiber Myopathy)
Carnitine used in treatment of which metabolic disorders
Carnitine (binds to and helps excrete
organic acids)
Born normal Severe early (within 6m) Dev regression and FTT
AR trait family history may be present
On exam have HSM, cherry red spot eye exam
Diagnosis?
Neimann-pick A
(deficient acid sphingomyelinase - low on testing lysosomal enzyme chr 11 therefore the protein accumulates)
B - like A but has pulmonary involvement
Treatment of GLUT-1 transporter disorder
Treat with the ketogenic diet 3-4:1 ratio
OR regular complex carbs plus oral ketones
Newborn screening includes
PKU • Hypothyroidism • CAH (not in Australia) • CF • Galactosaemia (not Victoria) • Expanded Newborn Screening: tandem mass spectrometry: FAOD’s, MSUD, some amino/organic acidemias • SCID, ALD, MPS and others coming….
Hurler treatment
Bone marrow transplant
• Enzyme replacement therapy
• Palliative (skeletal, cardiac, carpel
tunnel, behavioural)
• Prenatal testing is available
Presents with rigidity, dysarthria, dystonia
retinitis pigmentosa, progressive mental retardation, cognitive impairment, spasticity, tremors
Increased deposition of what in what syndrome?
Iron
Pantothenate kinase-associated neurodegeneration
Ectopia
lentis, tall stature
(marfinoid), thrombotic
Metabolic disease?
Homocystinuria
Early: Liver dysfunction. Renal tubular, cataracts.
Late: neuro and ovarian failure
Which disorder?
Galactosemia
Addisons like sx and neuro disease with characteristic MRI changes
Adrenoleukodystrophy
Even with mamanagemnt are people with PKU growth and development affected
Yes
Urinary glycosaminoglycans increased in which diseases
Lysosomal storage (not Neimann pick - diagnosed through white cell lysosomal enzyme levels sphingomyelinase)
Misty odour blonde blue eyes child normal at birth and then delayed, vomiting some eczema ? Cause
PKU
High succinylacetone in serum and urine diagnosis and treatment
Tyrosinaemia type 1
Tx: nitisinone
Number of metabolic disorders screened for in NZ
28
Manage Leigh disease with
Thiamine
Self injurious behaviour (biting lips) occurs with?
Lesch-Nyhan
Coma 3 days old
unable to break down the amino acids leucine, isoleucine and valine
Ketoaciduria
Maple syrup urine disease
Necrotic areas in CNS (looks similar to MS)
Leigh syndrome
Mitochondrial disorder
4 month old weak floppy with cardiomegaly (dilated cardiomyopathy)?
Pompe
Mutations in the GAA gene cause Pompe disease. The GAA gene provides instructions for producing an enzyme called acid alpha-glucosidase (also known as acid maltase). This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. The enzyme normally breaks down glycogen into a simpler sugar called glucose, which is the main energy source for most cells.
Mutations in the GAA gene prevent acid alpha-glucosidase from breaking down glycogen effectively, which allows this sugar to build up to toxic levels in lysosomes. This buildup damages organs and tissues throughout the body, particularly the muscles, leading to the progressive signs and symptoms of Pompe disease.
FTT and thromboembolic stroke can be presentation of
Homocysteinuria
Long bones Erlenmeyer flask appearance
Gauche
Hypersegmented neuts in
Folate deficiency
1 week old. Cataracts, vomiting since breast fed, E. coli sepsis with galactose-1-phosphate uridyl assay dx
Galactosaemia
Coarse fancies and hypoplasia Odontoceti process neck bones?
MPS VI or morquios syndrome
OTC deficiency is what kind of metabolic disorder
Urea cycle defect
Wrinkles tissue paper on cytomplasm in?
Gaucher disease
Foamy macrophages in?
Niemann-Pick disease
Boy with corneal opacity, decreased sweating and angiokeratomas on skin has?
(Can have vascular disease of kidney heart and brain too)
Fabry disease
Vascular glycosphingolipid deposition
Normal at birth prolonged jaundice then at 3 years degenerative and mild HSM
Specific sign is vertical supranuclear gaze palsy
Positive NPC gene
Other test and diagnosis?
Filipin stain positivity in cultures fibroblasts
Neiman-Pick C
