Metabolics

Question 1

what is the treatment for galactosemia

Answer 1

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

Question 2

what are the long term problems associated with galactosemia

Answer 2

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)

Question 3

what is the classical presentation of galactosemia

Answer 3

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

Question 4

what enzyme is deficient in galactosemia

Answer 4

galactose-1-phosphate uridyl transferase deficiency

Question 5

what makes up lactose

Answer 5

glucose and galactose

Question 6

how is galactosemia diagnosed?

Answer 6

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

Question 7

how is galactoseia inherited?

Answer 7

autosomal recessive

Question 8

what are the 3 key labs to order if you are worried about an IEM

Answer 8

glucose (many metabolic conditions have hypoglycemia)
ammonia
some measure of acid base status

Question 9

what is ammonia

Answer 9

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

Question 10

what IEM disorders should you consider if you have a high ammonia

Answer 10

urea cycle defects

organic acidemias

Question 11

how can you distinguish between urea cycle defect and organic acidemia

Answer 11

urea cycle infant: high ammonia and ALKALOSIS

organic acidemia: high ammonia and ACIDOSIS

Question 12

what is Gaucher disease

Answer 12

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

Question 13

what are some features of Gaucher disease

Answer 13

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

Question 14

what is one feature used to differentiate glycogen storage disease from Gaucher disease on physical exam

Answer 14

gaucher- splenomegaly

Question 15

what is Hurler syndrome

Answer 15

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)

Question 16

what is zellweger syndrome

Answer 16

defect in the biogenesis of the peroxisomes

the peroxisomes do not form properly

Question 17

what are some diagnostic features of zellweger syndrome

Answer 17

very high forehead
extremely large anterior fontanel
jaundice/hepatomegaly *
progressive kidney failure *
severe hypotonia *
narrow set eyes
broad nasal bridge

Question 18

what are the 3 main metabolic tests

Answer 18

plasma amino acids
urine organic acids
plasma acylcarnitine

Question 19

what is the urea cycle

Answer 19

converts ammonia to urea

primarily occurs in the liver

Question 20

what is the main test for urea cycle defect

Answer 20

plasma amino acids

Question 21

what bloodwork results are seen with a urea cycle defect

Answer 21

respiratory alkalosis ** huge clue to hyperammonemia
normal electrolytes and anion gap
elevated glutamine +/- Alanine

Question 22

what is the diagnostic test for UCD

Answer 22

molecular genetics testing

enzymology

Question 23

what is the treatment for UCD

Answer 23

stop protein
stop catabolism by giving IV glucose
replace Arginine!
provide alternate waste nitrogen pathway (IV NaBenzoate/NaPhenylacetate
dialysis- hemodialysis

Question 24

what is the most common UCD

Answer 24

OTC

ornithine transcarbamylase deficiency

Question 25

what lab findings are consistent with OTC

Answer 25

``` high ammonia high glutamine high alanine low citrulline low arginine low urea ```

Question 26

how does a patient with OTC present

Answer 26

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

Question 27

how can you differentiate CPS1 from OTC

Answer 27

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)

Question 28

what is the chronic management for urea cycle defect

Answer 28

low protein diet, with adequate calories and trace nutrients supplementation with urea cycle intermediates (ie arginine or citrulline) N2 scavengers- NaBenzoate, NaPhenylbutyrate liver transplant

Question 29

Homocystinuria

Answer 29

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

Question 30

physical features of homocystinuria

Answer 30

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

Question 31

what is the main side effect of pyridoxine (vit B6)

Answer 31

peripheral neuropathy

Question 32

what is the treatment for homocysteinuria

Answer 32

pyridoxine (B6) protein (methionine) restriction Betaine (converts homocysteine to methionine) Aspirin, heparin SC

Question 33

what two AA buildup with homocysteinuria

Answer 33

homocysteine and methionine

Question 34

what vitamins are required for homocysteine to make methionine and for conversion of methionine to homocysteine

Answer 34

B12 and folate | B6

Question 35

what amino acids build up with propionic/methylmalonic acidemias

Answer 35

``` VOMIT V- valine O- odd chain fatty acids M- methionine I- isoleucine t- threonine ``` MMA will be high in the urine with methylmalonic acidemia

Question 36

what is the diagnostic test for propionic/methylmalonic acidemias

Answer 36

urine organic acids

Question 37

what urea cycle disorders do we screen for on newborn screening

Answer 37

citrullinemia and ASA lyase deficiency | NOT: NAGS, CPS and OTC

Question 38

what is adrenoleukodystrophy

Answer 38

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

Question 39

what is PKU? tx?

Answer 39

``` phenylalanine hydroxylase deficiency elevated phenylalanine low or normal tyrosine tx: diet restriction of phenylalanine does not present acutely ```

Question 40

how does MCAD present? tx?

Answer 40

hypoketotic hypoglycemia * do not tolerate fasting, triggered by minor illness tx: avoid fasting and catabolism most common b oxidation disorder

Question 41

what is the treatment for Gaucher disease

Answer 41

enzyme replacement, miglustat

Question 42

how do organic Acidemias present

Answer 42

acute encephalopathy | anion gap acidosis, hyperammonemia, hypoglycemia

Question 43

how do urea cycle defects present

Answer 43

hyperammonemia, NO acidosis, NO hypoglycemia amino acids may point to the diagnosis tx: nitrogen scavenger meds Nabenzoate, phenylbutyrate

Question 44

what are the treatment options for MPS/Hurler syndrome

Answer 44

enzyme replacement therapy | bone marrow/stem cell transplant

Question 45

what is the best test to diagnose a patient with a mitochondrial disorder

Answer 45

muscle biopsy

Question 46

``` hypoglycemia + hepatomegaly isolated hypoglycemia hypoglycemia without ketosis hypoglycemia + hyponatremia/hypotension hypoglycemia + acidosis/ketosis ```

Answer 46

hypoglycemia + hepatomegaly = GSD isolated hypoglycemia = hyperinsulinemia hypoglycemia without ketosis = fatty acid oxidation defect hypoglycemia + hyponatremia/hypotension = adrenal insufficiency hypoglycemia + acidosis/ketosis = organic aciduria

Question 47

Fabry disease

Answer 47

``` 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 ```

Question 48

who to refer to metabolic (8)

Answer 48

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