Metabolics

Question 1

Hyperammonemia, what to check next

Answer 1

Assess for acidosis and ketouria

Question 2

Etiologies of hyperammonemia and acidosis without ketosis

Answer 2

FAOD

Question 3

Hyperammonemia without acidosis or ketosis etiology

Answer 3

Check plasma citrus line

Question 4

Hyperammonemia with ketosis and acidosis etiology

Answer 4

Lactic acidemia
Glutaric aciduria
Pyruvate carboxylase deficiency
B methylcrotonyl glycinuria
Propionic, methylmalonic and isovaleric acidurias

Question 5

Initial evaluation of an infant with possible metabolic disorder

Answer 5

CBC (for neutropenia and thrombocytopenia)
Electrolytes and arterial blood gas (for acidosis/alkalosis, anion gap)
Glucose
Calcium
Plasma ammonia
Lactate and pyruvate
LFTs
PT
Ketones
Reducing substances
NBS

Question 6

Secondary evaluation for targeted eval of infant with possible metabolic disorder

Answer 6

PAA
UOA
plasma carnitine and acylcarnitine profile
Plasma uric acid
BHOB and FFA
CSF amino acid analysis
Peroxisomal function tests

Question 7

Galactosemia cause, inheritance, symptoms

Answer 7

Galactose 1 phosphate uridyl transferase - if absent classic Galactosemia

AR

Poor feeding, vomiting, jaundice, liver failure, lethargy, renal, tubular, dysfunction, hepatomegaly , E. coli infections

Labs: increased LFT, increased indirect bili and later elevated d bili, low glucose, increased galactose in urine

Question 8

Next steps after abnormal galactose on NBS

Answer 8

Change to non lactose diet
Check lft, urine reducing substances, galactose 1 phosphate
Quantitative rbc GALT assay 

Question 9

Galactokinase deficiency
Inheritance, clinical presentation, abnormal newborn screen 

Answer 9

AR
Cataracts
If elevated galactose and normal RBC GALT
Test for urine reducing substances and then test for galactokinase if present reducing substances OR test epimerase if absent reducing substances

Question 10

Glycogen storage diseases that effect liver

Answer 10

Also have direct influence on blood glucose
Type I (Von gierke), 6 (Hers), 8

Question 11

GSD that effect muscle and anaerobic work

Answer 11

Type 5 (mcardle) and 7 (tarui)

Question 12

GSD that effect both liver and muscle

Answer 12

Type 3 (Forbes)

Question 13

GSD that affect various tissues yet no direct effect on blood glucose or anaerobic function

Answer 13

Type 2 (pompe) and type 4 (Andersen)

Question 14

Neonatal presenting GSD

Answer 14

Von gierke (type 1) and pompe (type 2)

Question 15

Type 1 GSD enzyme deficiency

Answer 15

Glucose 6 phosphatase

Question 16

Type 2 GSD enzyme deficiency

Answer 16

Lysosomal alpha glucosidase

Question 17

Deficiencies that cause hereditary fructose intolerance

And lab findings

Answer 17

Fructokinase
Fructose 1-phosphate aldolase

Findings: low glucose because of blockage of glycogenolysis (F1P inhibits phosphorylase activity and inhibits gng)
Absence of enzyme F1P adolase
Abnormal LFTs
Reducing substances in urine

Question 18

Urea cycle defects presentation

Answer 18

Majority present after age 1 or 2 days
Poor oral intake
Vomiting
Tachypnea
Lethargy followed by hypotonia
Seizures
Signs of liver disease

Question 19

Lab findings of UCD

Answer 19

Severe hyperammonemia
Primary resp alkalosis (maybe from cerebral edema if hyoerammonemia)
Normal glucose

Question 20

UCD pathway

Answer 20

Page 102 of review book

Question 21

how to diagnosis UCD

Answer 21

SAA
UOA (orotic acid)
Fibroblast or hepatocyte enzyme activity

Question 22

Diagnosis for N acetylglutamate synthetase

Answer 22

Glutamine/alanine: high
Urine orotic acid: low
Citrulline: low
Arginine: low

Question 23

Diagnosis of Carbamyl phosphate synthetase

Answer 23

Glutamine/alanine: high
Urine orotic acid: low
Citrulline: low
Arginine: low

Question 24

Diagnosis of ornithine carbamyl transferase

Answer 24

Glutamine/alanine: high
Urine orotic acid: high
Citrulline: low
Arginine: low

Question 25

Diagnosis of argininosuccinic acid synthetase

Answer 25

Glutamine/alanine: high Urine orotic acid: high Citrulline: high Arginine: low

Question 26

Diagnosis of arginosuccinic lyase deficiency

Answer 26

Glutamine/alanine: high Urine orotic acid: high Citrulline: high Arginine: low

Question 27

Deficiency of arginase to argininemia diagnosis

Answer 27

Glutamine/alanine: high Urine orotic acid: high Citrulline: high Arginine: high

Question 28

Treatment of UCD - hyperammonemia

Answer 28

Neurologic outcomes correlate with duration of hyperammonemia Hydration Remove nitrogen via medications (sodium benzoate and sodium phenylacetate) - renal function necessary because excreted in urine Hemodialysis if ammonia >500 Eliminate protein and minimize catabolism Provide IV glucose Supplement with arginine

Question 29

Maple syrup urine disease deficient

Answer 29

Ketoacid dehydrogenases that require thiamine

Question 30

Maple syrup urine disease lab findings

Answer 30

Send urine ketones, SAA, UOA Ketonuria Hypoglycemia Maple syrup urine odor Metabolic acidosis Urine dinitrophenylhydrazine test -> forms white precipitates Definitive: ketoacid dehydrogenase assay of skin fibroblasts of WBCs Prenatal dx: decreased keroacid dehydrogenase activity in cultured amniocytes or choriovillus cells

Question 31

Maple syrup urine disease s/s

Answer 31

Usually within first few days to weeks Poor feeding Vomiting Lethargy Tachypnea Death if untreated By 4 days, neurologic abnormalities: lethargy, irritability, alternating hypotonia and hyerptonia, dystonia, apnea, seizures, signs of cerebral edema

Question 32

MSUD neurologic outcome a/c

Answer 32

Correlate with plasma leucine concentrations