Metabolic/Thermal

Question 1

What are symptoms of galactokinase deficiency? Galactose-1-phosphate-uridyltransferase deficiency?

Answer 1

Galactokinase: only symptom is cataracts
Galactose-1-phosphate-uridyltransferase: galactosemia (AR, poor feeding, vomiting, cataracts, E. coli sepsis) Inc risk of premature ovarian failure, even if treated well. Cataracts usually regress once treated.

Question 2

How to diagnose galactosemia?

Answer 2

Low glucose
Elevated urine reducing substances
Hyperchloremic metabolic acidosis (normal lactate and pyruvate)
Newborn screen

Question 3

What are symptoms of galactokinase deficiency?

Answer 3

Cataracts, HIGH glucose
High urine reducing substances
High galactose

Question 4

What is Pompe disease?

Answer 4

Glycogen storage disorder (type II)
Deficiency of lysosomal alpha glucosidase
Symmetric severe muscle weakness with big failing heart
Die within 1 year

Question 5

What is von Gierke disease?

Answer 5

Type I glycogen storage disease
Glucose 6 phosphatase deficiency
Causes lactic acidosis (only type that does this) with low glucose. Inc risk of infections, hepatomegaly, bleeding disorder 2/2 liver failure
Prog: early death if no treatment

Question 6

What is fructosemia?

Answer 6

Autosomal recessive
Fructose intolerance
Def of fructokinase or fructose 1-phosphate aldolase
Will present once having cows milk protein formula or when eating fruits/veggies
Sx: low glucose, high urine reducing substances

Question 7

What is most common urea cycle defect?

Answer 7

Ornithine carbamyl transferase
X linked recessive
Elevated urine orotic acid
High ammonia

Question 8

What are sx of argininosuccinic acid synthetase?

Answer 8

Urea cycle defect
Citrullinemia (very very high)
Brittle hair
Orotic aciduria, with high ammonia

Question 9

What are sx of arginosuccinic lyase?

Answer 9

Autosomal recessive urea cycle defect

Bottle hair, elevated citrulline with orotic aciduria and only when severe has high ammonia

Question 10

What are sx of arginase deficiency?

Answer 10

Argininemia (can’t make urea from arginine)
Autosomal recessive urea cycle defect
Progressive spastic diplegia
Orotic aciduria

Question 11

What causes the respiratory alkalosis in urea cycle defects?

Answer 11

Hyperventilation 2/2 cerebral edema caused by hyperammonemia

Question 12

What will be high in all urea cycle defects?

Answer 12

Glutamine and alanine

Question 13

What determines neurologic outcomes in urea cycle defects?

Answer 13

Duration of hyperammonemia

Question 14

What becomes an essential amino acid in most urea cycle disorders?

Answer 14

Arginine (except in arginase deficiency)

Question 15

What is Maple Syrup Urine Disease?

Answer 15

Disorder of metabolism of branched chain amino acids (leucine, isoleucine, valine)
Autosomal recessive
Ketoacids in urine = maple syrup odor in urine

Question 16

How to dx maple syrup urine disease

Answer 16

Elevated urine organic acids (ketoacids of leucine, isoleucine, valine)
Urine dinitrophenylhydrazine test - will have white precipitates if excess branched chain ketoacids

Question 17

What determines cognitive outcomes in Maple Syrup urine disease?

Answer 17

Plasma leucine concentrations

Question 18

What is PKU?

Answer 18

Phenylketonuria
Autosomal recessive
Can’t digest phenylalanine
Musty or mousy odor

Question 19

What is most common cause of PKU?

Answer 19

Phenylalanine hydroxylase deficiency (can’t convert phenylalanine to tyrosine). Will have high phenylalanine and normal/low tyrosine

Question 20

What is tyrosinemia?

Answer 20

Autosomal recessive
Deficiency of fumarylacetoacetate hydrolase-> toxins accumulate leading to severe liver disease
Can have albinism, FTT, hepatic cancer

Question 21

How to diagnose tyrosinemia? How to treat?

Answer 21

High tyrosine levels, normal blood phenylalanine
Will have elevated blood and urine succinylacetone
Treat: avoid phenylalanine, tyrosine, methionine
Use nitisinone to prevent breakdown of phenylpyruvate (only treatment that helps liver)
May need liver transplant

Question 22

What is homocystinuria?

Answer 22

Autosomal recessive
Most common is deficiency of cystathionine synthetase. High homocysteine (blood and urine) and high methionine
Sx: downward dislocated lens, tall with fragile bones, stiff joints, dev delay.
*usually asymptomatic in neonatal period
Rx: pyridoxine/B6 (cofactor), decrease methionine, supp cysteine and folate

Question 23

What is nonketotic hyperglycinemia?

Answer 23

Autosomal recessive
Impacts fetus!
Sx quick, by 48 hrs. Severe lethargy, seizures. Agenesis of corpus callosum. Hiccups.
High glycine everywhere but no ketones
No treatment, very bad prognosis. Can try sodium benzoate and Valium to decrease seizures

Question 24

Histidinemia

Answer 24

Deficiency of histidase
Usually benign, some mental def, speech issues
High blood and urine histidine
Add ferric chloride to urine -> blue green (detects imidazole pyruvate acid)

Question 25

Cystinuria

Answer 25

Deficiency of cysteine (problem with amino acid transport across cell membrane) High cysteine in urine, low in blood Dx: nitroprusside urine test (detects ketoacids)

Question 26

Lysinuric protein intolerance

Answer 26

Abnormal amino acid transport across cell membrane -> deficiency of lysine, arginine, and ornithine Sx: ok if breastfed until protein increases, then FTT, lethargy High ammonia Rx: supplement with citrulline

Question 27

Hartnup disease

Answer 27

Defect in amino acid transport leading to deficiency of tryptophan Presents childhood/later in life Pellagra-like skin, ataxia, dev delay/sz Dx: hyperaminoaciduria with normal/low plasma amino acids

Question 28

Isovaleric acidemia

Answer 28

Abnl leucine metabolism (autosomal recessive) Deficiency of isovaleryl-CoA dehydrogenase *sweaty feet odor* Poor feeding, vomiting. 50% neonatal mortality Met acidosis with high ammonia, usually normal glucose Rx: glycine (to increase nontoxic isovalerylglycine production), restrict protein

Question 29

3-methylcrotonyl glycinuria

Answer 29

Downstream one step from isovaleric acidemia, presents 6m-3y *odor of male cat urine* Met acidosis, high ammonia, low glucose Dx: elevated 3-hydroxyisovaleric acid and 3-methylcrotonylglycine Rx: restrict protein, give biotin (cofactor)

Question 30

Proprionic acidemia

Answer 30

Autosomal recessive Deficiency of propionyl-CoA carboxylase Dysmorphic (high forehead, broad nose), FTT, dev delay, big liver. Inc infections Ketones AND high glycine, with high ammonia (can have low sugar)

Question 31

Methymalonic acidemia

Answer 31

Another Ketotic hyperglycinemia (like propionic acidemia). Def of methylmalonyl-CoA isomerase Same sx, ketones, high glycine, high ammonia Rx: abx, vitamin B12 aka cobalamin (cofactor)

Question 32

Mevalonic aciduria

Answer 32

Defect of mevalonate kinase (cholesterol synthesis pathway) Sx: FTT, dev delay, dysmorphic Dx: no metabolic acidosis, sugar normal, inc creatine kinase, increased mevalonic acid. Test skin fibroblasts or WBCs for enzyme activity. Rx: high cholesterol diet

Question 33

Glutaric aciduria type I

Answer 33

Autosomal recessive Deficiency of glutaryl-CoA dehydrogenase. Presents after 1 year with decompensation with infection Big head, progressive neuro sx Dx: low glucose, high ammonia, high urine glutaric acid levels. Frontotemporal atrophy of brain Rx: carnitinen and riboflavin (B12) supp

Question 34

Hydroxymethylglutaryl-CoA lyase deficiency

Answer 34

Causes hypoketotic hypolgycemia Last step in ketone synthesis from fatty acids Seizures, hypotonia Rx: frequent feeds, high carb diet

Question 35

What is most common fatty acid oxidation disorder?

Answer 35

Medium chain acyl-CoA dehydrogenase deficiency (MCAD) | Can’t oxidize FA completely -> hypoketotic hypoglycemia, severe acidosis

Question 36

Long chain 3-hydroxylacyl-CoA deficiency (LCHAD)

Answer 36

Deficiency of 3 hydroxylacyl coa dehydrogenase Autosomal recessive FTT, cardiomyopathy, higher mortality than MCAD *heterozygous LCHAD pregnant women can get acute fatty liver disease Sx: nonketotic hypoglycemia, high ammonia. Rx: supp with MCT to bypass defect, carb rich frequent meals

Question 37

Carnitine deficiency

Answer 37

Lethargy, muscle weakness, cardiomyopathy Important cofactor in transport of long chain FA across mitochondrial membrane Leads to hypoketotic hypoglycemia

Question 38

Glutaric aciduria type II

Answer 38

Multiple acyl-CoA deficiency Hypotonia, coma, dysmorphic (big forehead, flat nose) Smells like *sweaty feet* Causes met acidosis, low sugar, abnl urine organic acids

Question 39

What are signs of mucopolysaccharidosis?

Answer 39

Dystosis multiplex Alder-Reilly bodies in WBCs Urine mucopolysaccharides

Question 40

What kind of diseases have macular cherry red spots?

Answer 40

Lysosomal storage diseases affecting lipid storage and brain Example: Niemann-Pick A

Question 41

How to differentiate Gaucher I, Neimann-Pick A, and Tay sachs?

Answer 41

All are lipid lysosomal storage disorders Gaucher - HSM but normal eyes and brain Neimann-Pick A - cherry red spots on retina (50%), HSM, and CNS disease Tay-sachs - cherry red spots and cns disease, NO hsm.

Question 42

What are important mitochondrial disorders? Main sx?

Answer 42

Pyruvate dehydrogenase complex deficiency Pyruvate carboxylase deficiency Sx: severe lactic acidosis and neuro abnormalities (will have high pyruvate)

Question 43

Biotinidase deficiency

Answer 43

Same sx as biotin deficiency Alopecia, rash, immune deficits. Can lead to deafness, blindness, seizures if not dx and Rx. Rx: biotin supplement

Question 44

Wilson disease

Answer 44

Abnl copper transport, copper deposits everywhere Liver disease CNS disease as adult Cornea with Kayser-Fleischer rings Dx: low ceruloplasmin with only slight decrease in copper Rx: D-penicillamine to chelate copper, rarely liver transplant

Question 45

Menkes disease

Answer 45

``` X linked recessive Defect in copper transport, poor absorption of copper Brittle kinky steely hair Dev delay, sz, progressive CNS sx Big sagging lips, abnl eyebrow Osteoporosis, skin/joint laxity Tortuous arteries Low ceruloplasmin AND low copper Rx: daily copper injections ```

Question 46

Zellweger syndrome

Answer 46

Aka hepatocerebrorenal syndrome Decreased peroxisomal function, limited oxidation of long chain FA Dysmorphic (high forehead, wide fontanel, flat nose and orbital ridge) FTT, seizures, cataracts, glaucoma Dx: absent or decreased peroxisomes, high VLC FA, bile acid accumulation Rx: None, die by 1 year

Question 47

Which disorders cause sweaty feet odor?

Answer 47

Isovaleric acidemia | Glutaric aciduria type II

Question 48

What causes urine to smell like male cat urine?

Answer 48

3-methylcrotonyl glycinuria | Multiple carboxylase deficiency

Question 49

What are results of ferric chloride urine test?

Answer 49

Blue green -> PKU Green/gray -> MSUD Green -> tyrosinemia

Question 50

How is neonatal heat loss different from adult?

Answer 50

4x greater