amino acid disorders + urea cycle disorders + lipid disorders

Question 1

amino acid disorders discussed in this class

Answer 1

phenylketonuria (PKU)

maple syrup urine disease (MUSD)

alkaptonuria

Question 2

PKU inheritance + general

Answer 2

autosomal recessive

impaired ability to metabolize phenylalanine

Question 3

PKU genetic abnormality

Answer 3

mutations involving loci encoding for PAH on chromosome 12q

mutations include substitutions, insertions, deletions

Question 4

PKU

enzyme affected

Answer 4

phenylalanine hydroxylase (PAH)

Question 5

PKU

effect on substrate/byproduct

Answer 5

buildup of phenylalanine

Question 6

PKU

pathophys

Answer 6

elevated levels of plasma phenylalanine that disrupts essentail cellular proccesses in the brain and eventually causes mental retardation

PKU levels of phenylalanine are 6-80 mg/dl (normal is 1 mg/dl)

Question 7

PKU

clinical manifestations

Answer 7

untreated PKU has severe mental retardation

normal at birth then progressive developmetnaly delay

must catch early and control

Question 8

PKU

expression/penetrance

Answer 8

disease freq. varies by population

turkey has high incidence rate

high in yeminite jewish populaiton, northern/eastern europe, italy, and china

Question 9

PKU treatment

Answer 9

restoring normal blood phe levels thru restricting dietary phe

strong relationship exists between control of blood phe levels in childhood and IQ

Question 10

rare autosomal recessive diorder that involves defects in catabolic pathway of branched chain amino acids

Answer 10

maple syrup urine disease

Question 11

MUSD

genetic abnormality

Answer 11

caused by mutaiton of 1 of 6 loci that envode for the branched chain amino acid complex (BCKAD complex)

Question 12

BCKAD complex

Answer 12

composed of 4 catalytic components and 2 regulatory enzymes

most mutations occur in the catalytic compenent section

normally involved in decarboxylation of alpha keto acids of branched chain AAs to their acyl-CoA

Question 13

MUSD

enzyme affected

Answer 13

BCKAD Complex

Question 14

branched chain amino acids

Answer 14

leucine, isoleucine, valine

Question 15

effect on substrate/byproduct

MUSD

Answer 15

accumulation of branched chain amino acids (valine, leucine, isoleucine)

Question 16

leucine accumulation

Answer 16

neurological symptoms bc it is transported rapidly across BBB and metabolized to yield presumably glutamate and glutamine

Question 17

elevation of plasma isoleucine…

Answer 17

maple syrup odor of urine

Question 18

clinical manifestation of MSUD

Answer 18

accumulation of any of the 3 AA leads to encephalopathy and progressive neurodegeneration in infants not treated

poor feeding, vomiting, failure to thrive, increased lethargy

Question 19

MSUD expression and prevalance

Answer 19

more prevalant in populations with high frequency of consanguinity

ex. mennonite community of Lancaster County, PA

symptoms devleop in neonates aged 4-7 days

variability

Question 20

MSUD

treatment

Answer 20

early diagnosis and diet intervention to prevent complications and allow normal IQ

dietary restriction of branched chain AAs to only what is minimally needed

thiamine supplement

Question 21

Alkapotnuria

Genetic abnormality

Answer 21

HGO gene

defect in catabolic pathway of tyrosine

Question 22

intermediate product of tyrosine catabolic pathway

Answer 22

homogentisic acid

Question 23

Alkapotnuria

enzyme affected

Answer 23

deficiency of HGO

Question 24

Alkapotnuria

effect on substrate/byproduct

Answer 24

deficiency of HGO causes accumulation of homogentisic acid

homogentisic acid is rapidly cleared in kidney and excreted

Question 25

Alkapotnuria

Answer 25

Plasma homogentisic acid is originally low due to rapid kidney clearence *however* w/time it is *depostited in cartilage throughout the body* resulting in a build up of dark pigment (**onchronosis**) normally transparent tissues will become slate blue

Question 26

Alkaptonuria clincial manifestations

Answer 26

upon contact with open air, homogentisic acid is ozidized to form a pigment like polymeric material causes the **black color of standing urine** by 4th decade, tissues are slate blue *arthritis* (spine, lrg joints)

Question 27

Alkaptonuria expression

Answer 27

HGO shows a wide spectrum of mutation with high variability

Question 28

Alkaptonuria treatment

Answer 28

redution of Phe and Tyr reduces homogentisic acid excretion vitamin C supplement for older children and adults to reduce cartilage deposits

Question 29

urea cycle disorder discussed in this class

Answer 29

orinthine transcarbamylase deficiency

Question 30

orinthine transcarbamylase deficiency inheritance

Answer 30

X linked disorder (mostly in males, not females bc of X-inactivation)

Question 31

orinthine transcarbamylase deficiency enzyme

Answer 31

**orinthine transcarbamylase** deficiency used in urea cycle to detoxify and excrete nitrogen

Question 32

orinthine transcarbamylase deficiency clincial manifestations

Answer 32

excess nitrogen causing **severe hyperammonemia** in neonate (24-48 hrs after ingesting protein) progressive lethargy and decreased levels of conciousness Ias nitrogen levels increase) symptomatic females may displat headache or vomiting after consuming high protein meals and learning diabilities

Question 33

orinthine transcarbamylase deficiency expression/penetrance

Answer 33

primary affects males females be symptomatic

Question 34

orinthine transcarbamylase deficiency treatment

Answer 34

early, aggresive IV fluid, glucose, benzoic acid, penylacetate **high risk of recurrent hyperammonemia**

Question 35

lipid disorder discussed in this class

Answer 35

medium chain acyl-CoA Dehydrogenase (MCAD)

Question 36

most common fatty acid metabolic disorder

Answer 36

medium chain acyl-CoA dehydrogenase (MCAD)

Question 37

MCAD genetic abnormality

Answer 37

results from deficiency of medium chain acyl-coenzyme A dehydrogenase

Question 38

enzyme affected MCAD

Answer 38

medium chain -acyl coenzyme A dehydrogenase

Question 39

MCAD effect on substrate/byproduct

Answer 39

fasting results in **accumulation of fatty acid intermediates and exhausts gluclose supply**

Question 40

MCAD clinicla manifestations

Answer 40

**episodic hypoglycemia** *often provoked by fasting* may have vomiting and lethargy following fasting in children cerebal edema and encephalopathy

Question 41

MCAD treatment

Answer 41

support during times of nutritional stress eat enough calories and avoid fasting