Metabolics Flashcards
what is the treatment for galactosemia
soy formula (there is no lactose or galactose, it is made of sucrose) need to remove all galactose- containing foods from the diet along with adequate calcium supplementation
what are the long term problems associated with galactosemia
female infertility
ovarian failure with primary or secondary amenorrhea
speech dyspraxia
decreased bone mineral density
cognitive deficits (DD and learning disabilities that increase in severity with age)
what is the classical presentation of galactosemia
typically present in the second half of the first week of life
jaundice
hepatomegaly
vomiting
hypoglycemia
seizure
at increased risk for E.coli neonatal sepsis
pseudotumor cerebri can occur and cause a bulging fontanel
what enzyme is deficient in galactosemia
galactose-1-phosphate uridyl transferase deficiency
what makes up lactose
glucose and galactose
how is galactosemia diagnosed?
demonstration of a reducing substance in several urine specimens collected while the patient is on a diet containing lactose
direct enzyme assay using erythrocytes establishes the diagnosis
how is galactoseia inherited?
autosomal recessive
what are the 3 key labs to order if you are worried about an IEM
glucose (many metabolic conditions have hypoglycemia)
ammonia
some measure of acid base status
what is ammonia
the means by which the body clears nitrogen
indicator that you are turning over protein
ammonia serves as an indicator of catabolism and of failure in waste removal
what IEM disorders should you consider if you have a high ammonia
urea cycle defects
organic acidemias
how can you distinguish between urea cycle defect and organic acidemia
urea cycle infant: high ammonia and ALKALOSIS
organic acidemia: high ammonia and ACIDOSIS
what is Gaucher disease
one of the most common lysosomal storage diseases
due to a defect in the glucocerebrosidase gene (part of lipid membrane)
the most prevalent genetic defect among Ashkenazi Jews
what are some features of Gaucher disease
thrombocytopenia
splenomegaly **
hepatomegaly
bone pain/disease ** (erlenmeyer flask deformity, lytic lesions)
Pathologic hallmark of Gaucher disease is Gaucher cell in the RES, particularly the bone marrow
what is one feature used to differentiate glycogen storage disease from Gaucher disease on physical exam
gaucher- splenomegaly
what is Hurler syndrome
MPS-1
infants appear normal at birth but develop coarsening facial features
defect in alpha-iduronidase (an enzyme used to break down mucopolysaccharides)
hepatosplenomegaly
coarse facial features * (heavy brow)
corneal clouding *
large tongue * (protruding tongue, thickened gums)
flat nasal root *
enlarged head circumference
joint stiffness, flexion deformities
short stature
skeletal dysplasia (dysostosis multiplex), clawed hand
hypertrophic cardiomyopathy
Hunter syndrome- similar but x linked (only in boys and no corneal clouding)
what is zellweger syndrome
defect in the biogenesis of the peroxisomes
the peroxisomes do not form properly
what are some diagnostic features of zellweger syndrome
very high forehead extremely large anterior fontanel jaundice/hepatomegaly * progressive kidney failure * severe hypotonia * narrow set eyes broad nasal bridge
what are the 3 main metabolic tests
plasma amino acids
urine organic acids
plasma acylcarnitine
what is the urea cycle
converts ammonia to urea
primarily occurs in the liver
what is the main test for urea cycle defect
plasma amino acids
what bloodwork results are seen with a urea cycle defect
respiratory alkalosis ** huge clue to hyperammonemia
normal electrolytes and anion gap
elevated glutamine +/- Alanine
what is the diagnostic test for UCD
molecular genetics testing
enzymology
what is the treatment for UCD
stop protein stop catabolism by giving IV glucose replace Arginine! provide alternate waste nitrogen pathway (IV NaBenzoate/NaPhenylacetate dialysis- hemodialysis
what is the most common UCD
OTC
ornithine transcarbamylase deficiency
what lab findings are consistent with OTC
high ammonia high glutamine high alanine low citrulline low arginine low urea
how does a patient with OTC present
x linked disorder (females primrily asymptomatic)
infant appears normal at birth but becomes symptomatic following introduction of dietary protein
refusal to eat
vomiting
tachypnea
lethargy
seizures are common
hepatomegay
can have increased ICP with bulging fontanelle and dilated pupils
how can you differentiate CPS1 from OTC
marked increase in urinary orotic acid in patients with OTC deficiency helps differntiate this defect from CPS1 deficiency
CPSI- carbamoyl phosphate synthetase I (another type of urea cycle defect)
what is the chronic management for urea cycle defect
low protein diet, with adequate calories and trace nutrients
supplementation with urea cycle intermediates (ie arginine or citrulline)
N2 scavengers- NaBenzoate, NaPhenylbutyrate
liver transplant
Homocystinuria
inborn error of methionine metabolism
homocysteine is a metabolite of methionine (essential amino acid)
methionine- homocysteine- cystathionine- cysteine
caused by cystathionine b-synthase deficiency
they have large amounts of homocysteine in their urine
tx: may respond to high doses of vitamin B6
physical features of homocystinuria
eye: ectopia lentis, myopia
skeletal abnormalities resembling those of Marfan syndrome
tall with elongated limbs
scoliosis
pectus carinatum or excavatum
high arched palate
crowding of teeth
Vascular: recurrent arterial and venous thrombosis ***
CNS: psychiatric and behavioral disorders, developmental delay
what is the main side effect of pyridoxine (vit B6)
peripheral neuropathy
what is the treatment for homocysteinuria
pyridoxine (B6)
protein (methionine) restriction
Betaine (converts homocysteine to methionine)
Aspirin, heparin SC
what two AA buildup with homocysteinuria
homocysteine and methionine
what vitamins are required for homocysteine to make methionine and for conversion of methionine to homocysteine
B12 and folate
B6
what amino acids build up with propionic/methylmalonic acidemias
VOMIT V- valine O- odd chain fatty acids M- methionine I- isoleucine t- threonine
MMA will be high in the urine with methylmalonic acidemia
what is the diagnostic test for propionic/methylmalonic acidemias
urine organic acids
what urea cycle disorders do we screen for on newborn screening
citrullinemia and ASA lyase deficiency
NOT: NAGS, CPS and OTC
what is adrenoleukodystrophy
x-linked disorder
high levels of very long chain fatty acids found in the tissues and body because of impaired b-oxidation in the peroxisomes
present with hyperactivity, inattention, ataxia
what is PKU? tx?
phenylalanine hydroxylase deficiency elevated phenylalanine low or normal tyrosine tx: diet restriction of phenylalanine does not present acutely
how does MCAD present? tx?
hypoketotic hypoglycemia *
do not tolerate fasting, triggered by minor illness
tx: avoid fasting and catabolism
most common b oxidation disorder
what is the treatment for Gaucher disease
enzyme replacement, miglustat
how do organic Acidemias present
acute encephalopathy
anion gap acidosis, hyperammonemia, hypoglycemia
how do urea cycle defects present
hyperammonemia, NO acidosis, NO hypoglycemia
amino acids may point to the diagnosis
tx: nitrogen scavenger meds Nabenzoate, phenylbutyrate
what are the treatment options for MPS/Hurler syndrome
enzyme replacement therapy
bone marrow/stem cell transplant
what is the best test to diagnose a patient with a mitochondrial disorder
muscle biopsy
hypoglycemia + hepatomegaly isolated hypoglycemia hypoglycemia without ketosis hypoglycemia + hyponatremia/hypotension hypoglycemia + acidosis/ketosis
hypoglycemia + hepatomegaly = GSD
isolated hypoglycemia = hyperinsulinemia
hypoglycemia without ketosis = fatty acid oxidation defect
hypoglycemia + hyponatremia/hypotension = adrenal insufficiency
hypoglycemia + acidosis/ketosis = organic aciduria
Fabry disease
x-linked α-Galactosidase A deficiency present with recurrent severe pain in hands/ feet (precipitated by hot weather, stress, exercise, fatigue) angiokeratoma 2 enzyme replacement therapies
who to refer to metabolic (8)
Recurrent unexplained illness
Unexplained deterioration in clinical status
Liver disease, cholestasis, hepatomegaly (splenomegaly)
Myopathy, Myositis, Rhabdomyolysis
Cardiomyopathy
Unexplained seizures and/or neurological dysfunction
Progressive deterioration in mental status
Children with known or suspected genetic metabolic diseases or a
positive family history
