Inborn Errors of Metabolism Flashcards
(35 cards)
What are the classes of Metabolic Disorders?
1) Carbohydrate Metabolism
2) Amino Acid Metabolism
3) Lipid Metabolism Disorders
4) Organic Acid Metabolism
5) Urea Cycle Disorders
6) Energy Production Defects
7) Transport Defects
8) Metal Ion transporters
What is the most common carbohydrate deficiency?
What is it’s main metabolic disorder?
Classical Galactosemia (1 in 55k) - Cannot convert galactose to glucose efficiently.
What are the symptoms of Galactosemia?
1) Failure to thrive
2) Hepatic insufficiency
3) Cataracts
4) Developmental delay
5) In long term - poor growth and mental retardation
6) Screening by checking blood for enzyme activity, dietary restriction
What is the enzyme deficiency in classical galactosemia? What is the genetic mutation that effects this disorder?
Deficiency in Galactose -1- phosphate uridyl transferase.
Enzyme deficiency due to a missense mutation in exon 6
What is the main enzyme defect in Hereditary Fructose Intolerance?
What type of food begins to show signs of defect?
- defect in fructose 1,6 bisphosphate aldolase
in kidney cortex. - Fruit
What is the prevalence of Hereditary Fructose intolerance?
1 in 20,000
What is the main enzyme defect in Von Gierke Disease? Metabollically what is its affect?
- Main defect in glucose-6-phosphatase
- Glucose from glycogen not released from liver, G-6-P otherwise metabolized
What are the main organs affected by Von Gierke’s Disease?
What are the main symptoms associated?
- Liver, skeletal muscle, kidney affected.
- Hepatomegaly and hypoglycemia
What is the main enzyme defective in Phenylketonuria?
What cannot be made?
- Main defect in Phenylalanine hydroxylase gene (PAH)
- Phenylalanine cannot be converted into Tyrosine and thereby produce Dopamine–>Melanin or (via another pathway) Tyrosine can’t produce Fumarate and acetoacetate (krebs cycle?)
In PKU what is the main product buildup and what are its effects.
- Phenylalanine is the main buildup This causes disruption in : Myelination, protein synthesis, and eventual retardation. High level in pregnant mother can affect fetus
What cannot be metabolized in Maple Syrup Urine Disease?
- Cannot metabolize branched chain ketoacids from branched chain amino acids
In Maple Urine Disease what can the bi products lead to?
BCAA can lead to neurodegeneration and death in months
What is the enzyme defect in MCAD deficiency?
- Medium-chain acyl-coenzyme A dehydrogenase deficiency leading to fatty acid intermediates accumulation with insufficient ketone bodies, glycogen gone.
What are the presenting symptoms of MCAD deficiency?
Episodic hypoglycemia after fasting. Mutation due to a missense A–>G lysine–>glutamate conversion
- Vomiting and lethargy after minor illness
What is the treatment of MCAD deficiency?
-Provide usable calories (glucose),
What is the main problem win congenital Adrenal Hyperplasia?
What can excess precursors cause?
- Block in corticosteroid synthesis.
- Excess precursors can be androgenic or converted to weak androgens, virilization of females in utero
What are the main symptoms of the severe form of Congenital Adrenal Hyperplasia?
- Severe forms cause salt-wasting (peeing out Na+) - weight loss, lethargy, dehydration, death
Defects in what 4 enzymes cause an accumulation of precursors in the urea cycle? What would there symptoms be?
- Carbamoyl phosphate synthetase (CPS), Ornithine transcarbamoylase (OTC), Argininosuccinate synthetase (ASA), Argininosuccinase (AS).
- Symptoms: lethargy and coma
What amino acids are affected in Cystinuria?
What are the gene defects that lead to type I and type II and type III.
What defect do these genes result in?
- Cystine (obviously), Lysine, arginine, and ornithine all have high levels in urine.
- Type I mutates SLC3A1
- Type II and III mutates SLC7A9
- Defect in the heavy and light chains of the brush border aa transporter; Cystinosis (defective transporter for lysosomes–> stones in lysosomes)
What type of genetic inheritance is OTC deficiency passed from generation to generation?
- What type of carriers are women?
- What is the treatment?
- X-linked gene
- Women can be symptomatic carriers
- Treatment: sufficient calories and protein for normal growth and dev., prevent hyper-ammonemia from excess nitrogen.
What is the defect in Wilson Disease?
-Where and what results from the accumulations?
- Defect in copper excretion to biliary tract, leading to accumulations in liver, progressive liver disease and neurological abnormalities.
What are the main symptoms of Wilson’s Disease?
1) Acute or chronic liver disease
2) Dysarthria (diminished coordination
3) Arthropathy, Cardiomyopathy
4) Kidney damage, hypoparathyroidism
5) Kayser-Fleischer ring (green-brown ring in eye)
What is the gene defect that causes Wilson Disease?
ATP7B- Single missense in 40%
- Predominant expression in liver and kidney
- Adenosine triphosphatase with six tandem copies of metal-binding sequence.
What is the main physiological problem in Hereditary Hemochromatosis?
When does it normally appear in an individual?
- Excessive iron absorption in intestine that eventually accumulates in liver, kidney, heart, joints, pancreas.
- Incomplete penetrance (delayed onset with age) - 40 in men and 60 in women (menstration/menopause)
