Fatty acid oxidation

Question 1

3 steps of fatty acid beta oxidation

Answer 1

1. Fatty acid enters cell carried by albumin
2. Activation of fatty acid by acyl co-A synthase –> made into acyl CoA
3. Entry of fatty acid in mitochondria
   - long chains require carnitine shuttle
   - medium and small chains

Question 2

Carnitine transporter defect
Carnitine uptake defect
- clinical manifestations

Answer 2

INFANCY:

• hypoketotic hypoglycemia
• elevated liver enzymes
• hyperammonemia triggered by fasting or common illnesses

CHILDHOOD:
- myopathy involving heart and skeletal muscle

ADULTHOOD:
- fatigue, asymptomatic

Question 3

Carnitine transporter defect

• diagnosis
• prognosis

Answer 3

DIAGNOSIS

• plasma free and total carnitine low
• high urine carnitine
• molecular genetic analysis of SLC22A5

PROGNOSIS: with carnitine supplementation, excellent

Question 4

CPT IA deficiency

Answer 4

Carnitine not conjugated to long-chain FA

Hepatic encephalopathy precipitated by fasting or fever
Rapid onset of symptoms in association with a relatively common infectious disease, such as febrile or gastrointestinal illness

Question 5

CACT deficiency

Answer 5

Long chain fatty acylcarnitine unable to be transported across inner mitochondrial membrane

Rare
Usually presents in neonatal period with severe hypoketotic hypoglycemia, hyperammonemia
Cardiac arrhythmias and/or hypertrophy
Rare milder form

Question 6

CPT II deficiency

Answer 6

unable to release free carnitine into matrix

the most common of the carnitine shuttle disorders
variable presentation:
NEONATAL
- hypoglycemia, liver failure, cardiomyopathy
- *congenital brain and kidney abnormalities

INFANTILE

• hypoglycemia, liver failure, cardiomopathy
• myopathy

ADULTHOOD
- recurrent exercise or stress-induced myoglobinuria

Question 7

VLCAD deficiency

Answer 7

Early onset:

• hypoketotic hypoglycemia
• cardiomyopathy
• hepatomegaly

Childhood onset:

• hypoketotic hypoglycemia
• hepatomegaly

Adult onet:
- recurrent rhabdomyolysis with myoglobinuria

Question 8

MCAD deficiency

Answer 8

Hypoketotic hypoglycemia
Reye-like syndrome:
- hypoglycemia
-hyperammonemia
- elevated transaminases
- brain edema
- fatty liver
Sudden unexpected death

Question 9

SCAD deficiency

Answer 9

Symptomatic patients:

• failure to thrive, hypotonia
• many other symptoms, most of which of which have a questionable relationship to biochemical defect

Question 10

Multiple Acyl CoA Dehydrogenase Deficiency (MADD)

Diagnosis

Answer 10

All Acyl CoA DHs share flavoprotein as an electron acceptor
Deficiencies of ETF and ETF:CoQ oxireductase result in secondary deficiencies of all of the primary dehydrogenases

Diagnosis:

• urine organic acids
• blood acylcarnitines- C4-18 elevations
• Molecular genetic analysis
• enzyme assay

Question 11

MADD clinical features

Answer 11

TYPE I: neonatal onset with congenital abnormalities

TYPE II: neonatal onset, no congenital abnormalities

TYPE III: late-onset

neonatal forms - usually fatal

late-onset - variable

Question 12

LCHAD deficiency genetics

Answer 12

alpha-subunit gene of trifunctional protein HADHA

common mutation

Question 13

LCHAD deficiency symptoms

Answer 13

Hypoketotic hypoglycemia
Reye-like symptoms
- hypoglycemia
- hyperammonemia
- elevated transaminases
- hepatomegaly
- fatty liver
- brain edema
lactic acidosis
cardiomyopathy. myopathy
retinopathy
peripheral neuropathy
failure to thrive