Genetics Unit 27: Metabolic Diseases

Front 1

3 categories of inborn errors of metabolism

Back 1

1) Cellular poisoning of cell by abnormal metabolite or high concentrations of normal metabolites.
2) Energy deficient
3) Mixed types

Front 2

Types of Cellular Poisoning IEM

Back 2

Small molecules:
-aminoacidopathies
-organic acidurias
-urea cycle defects
Large molecules:
-Lysosomal storage disease
-glycogen storage disease

Front 3

Types of Energy deficient IEM

Back 3

Congenital lactic acidemias
mitochondrial enzyme defects
fatty acid oxidation defects

Front 4

Types of mixed types of IEM

Back 4

peroxisomal defects

Front 5

Whats the difference between diseases which deal with small (diffusable) substrates vs large (macromolecules)?

Back 5

Pathology for macromolecule diseases is confined to the tissues where the substrate is accumulating while smaller molecules are more unpredictable with their ability to diffuse and damage other cells.

Front 6

PKU presentation

Back 6

Seem normal at birth, may have a mousy odor. Should be considered if a newborn presents with sepsis-like symptoms.

Front 7

PKU untreated consequences

Back 7

Severe mental retardation, pigment dilution, rash, seizures, microencephaly.

Front 8

PKU Diagnosis

Back 8

Elevated serum phenylalanine, can do genetic testing.

Front 9

What causes the pathology of PKU

Back 9

Normal metabolite in abnormal amounts. While enzyme is only located in the liver, disorder is in brain. Is a multifactorial disorder (must be exposed to dietary phenyalanine.

Front 10

Benign Hyperphenylalaninemias

Back 10

Also due to a PAH deficiency but not as severe. Can respond to a low protein diet alone.

Front 11

PKU genetics

Back 11

Deficient PAH activity. Most people are compound heterozygotes of 4 common alleles.

Front 12

Defects in BH4

Back 12

Will present with what seems to be benign hypephenylalaninemias but will actually have a more severe disorder (this is also checked for when elevated phenylalanine is measured).

Front 13

Maternal PKU

Back 13

Caused by women with PKU who dont maintain diet and then give birth. Can cause problems with baby.

Front 14

Clinical tells for someone having acute PKU effects

Back 14

Hyperreflexive and lighter colored hair (means they havent been sticking to their diet). These changes are reversible.

Front 15

Urea cycle defect presentation

Back 15

normal for first 24-48. Protein intake followed by lethargy, vomiting, seizures, and eventually coma.

Front 16

Urea cycle enzyme deficiency pathology and mech.

Back 16

Ultimately leads to elevated ammonia and glutamate levels resulting in encephalopathy and death.

Front 17

Urea cycle enzyme deficiency treatment

Back 17

Low protein diet, arginine supplementation, and sodium benzoate/phenylacetate/phenylbutyrate to increase ammonia excretion.

Front 18

Urea cycle enzyme deficiency diagnosis

Back 18

Severe hyerammonemia, respiratory alkalosis, abnormal serum AAs.

Front 19

Galactosemia genetics

Back 19

Autosomal recessive disorder. Can be caused by deficiencies in GALT/GPUT, galactokinase, and epimerase

Front 20

Galactosemia presentation

Back 20

Appear normal at birth. Symptoms begin first week of life after lactose if given:
-Vommitting/diarrhea
-E.coli sepsis
-FTT
-Hepatomegaly and jaundice
-Cataracs
-Cerebral adema

Front 21

Galactosemia diagnosis

Back 21

Galactosemia/galactosuria, hypophosphatemia, hypokalemia, hypoglycemia

Front 22

Galactosemia pathology

Back 22

Will be fatal by 2 weeks if untreated. Mental retardation if delayed treatment. Women can get ovarian failure regardless.

Front 23

Galactosemia treatment

Back 23

Soy formula, no dairy, no high galactose fruits, calcium supplementation.

Front 24

MCAD deficiency presentation

Back 24

Patients between 5-24 months present with vomiting, lethargy, hypotonia, difficulty feeding, and coma usually with a history of fasting.

Front 25

MCAD Diagnosis

Back 25

Hypoketotic, hypoglycemia, mild hyperammonemia, low carnitine, mild enlargement of liver and abnormal liver function.

Front 26

MCAD treatment

Back 26

Intrevenous glucose and hydration, L-carnitine, and avoidance of fasting.

Front 27

MSUD disease mech

Back 27

Disorder in BCAA metabolism resulting in elevated levels of leucine, isoleucine, and valine.

Front 28

MSUD presentation

Back 28

Appear normal at birth. IN first week of life develop vomiting, lethargy, high pitched cry, neuro deterioration, seizures, coma, death. Kids urine smells like maple syrup.