Inborn Errors of Metabolism Flashcards
What is the most common carbohydrate defect?
symptoms include: failure to thrive, hepatic insufficiency, cataracts, developmental delay, poor growth and development
What enzyme is mutated in this disease?
How do we screen for it?
Galactosemia
Galactose-1-phosphate uridyl transferase
OR
galactokinase gene
cannot convert galactose to glucose-- uses alternative pathway galctitol and galactonate
check blood for enzyme activity
What disease is appears after adding fruit to the diet?
Symptoms: fruit makes children noxious
What enzyme is defective?
Hereditary fructose intolerance
fructose 1,6-bisphosphate aldolase
What disease is caused characterized by the following symptoms?
hypoglycemia, hepatomegaly, no sleeping through the night
What defectve enzyme is responsible?
Von Gierke Disease
glucose-6-phosphate
What is the most common cause of hyperphenylalenemia?
What body processes are disrupted by hyperphenylanenmia?
How do we screen for it?
How can it be managed?
Phenylketonuria
defect in phenylalanine hydroxylase, which converts phyenylalanine to tyrosine
disrupts myelination, protein synthesis, and developmental delays
All newborns are tested
low levels of phenylalanine while getting enough protein & tyrosine
What disease is characteized by brown, maple syrup smelling urine?
What enzyme is deficient in this disease?
Maple Syrup Urine Disease
branched chain ketoacid dehydrogenase
accumulation of by-products leads to neurodegeneration and death; it is not mamagable
common in Mennonites of Lancaser, PA
What is the most common fatty acid disease?
Symptoms: episodic hypoglycemia after fasting; vomiting, lethargy after minor illness; can become comatose and die
What enzyme is deficent in these individuals?
How is it treated?
MCAD deficiency
medium-chain acyl-coenzyme A dehydrogenase
fatty acid intermediates accumulate, insufficient ketone bodies, glycogen gone
supportive care, provide usable calories (glucose), avoid fasting
missense A-G
What disease occurs when corticosteroid synthesis is blocked?
What are the symptoms of this disorder? Severe forms?
21 Hydroxylase (CYP21) deficiency
excess precursors can be adrogenic or weak androgens
virilization in females; ambiguous genetalia
severe forms caus salt-washing (low sodium levels, weight loss, lethargy, dehydration, death)
What disease is the most sever of the peroxisome disorders?
Symptoms?
What enzyme is mutated?
Zellwegger
neonatal hypotonia, progressive white matter disease, distincitive face, death in infancy
mutations in proteins needed for peroxisome biogenesis & importing proetins into matrix
What happens in lysosomal storage disorders?
materials that lysosomes degrade accumulate in tissuses and cause dysfunction
(mucopolysaccharides, sphingolipids, glycoproteins & glycolipids)
What type of lysosomal storage disorder is caused by a reduced degradation of glycosaminoglycants (heparan sulfate, dermatan sulfate, keratan sulfate, chondroitin sulfate)?
How are the diseases within this type similar and different?
What are the symptoms of this type of disorder?
Which 3 cause developmental delay?
Mucopolysaccharidoses
autosoma recessive (except hunter = X-linked)
chronic, progressive multisystem deterioation
problems with hearing, vision, joint & cardiovascular system (abnormal facial features)
Developmental delay (hunter, hurler, sanfilippo)
What type of lysosomal storage disorder is caused by deficient sphingolipid degradation?
What are the 3 well-known disorders that fall under this category and their associated enzyme deficiency?
Sphingolipidoses
- Gaucher (beta-glyucosidase deficienty)
- rare, except in Ashkenzi Jews
- shows up in kids
- nose bleeds, hepatosplenomegaly, fractures
- Tay-Sachs (beta-hemosaminidase A deficienty)
- hypotonia at birth, cherry red spot on macula of eye, by 6 mo go backwards in development, dont reach 2 yrs
- Niemann-Pick (sphingomyelinase deficienty)
- poor prognosis
What enzyme is deficient in I-cell disease?
What is the physiological impact of this?
deficient phosphotransferase
mannose-6-phosphate signal is not added to enzymes, which targets them for the lysosome
accumulated products appear as inclusions
Defects in which 4 urea cycle disorders cause accumulation of precursors, lethary and coma (high ammonia)?
- Carbamoyl phosphate synthetase (CPS)
- ornithine transcarbamoylase (OTC)
- Argininosuccinate synthetase (ASA)
- Arginosuccinase (AS)
What is the most common urea cycle defect? Why?
What symptoms are seen by carriers?
How can it be maintained?
OTC deficiency b/c it is X-linked
women can be symptomatic carriers
women who are symptomatic carriers can get strong headaches after eating protein
need sufficient calories and protein, but was to prevent hyperammonemia from excess nitrogen
What symptoms are characteristic of Cystinuria? What is it caused by?
What are the 2 types?
cystinuria causes a problem with the transporter for dibasic amino acids & high levels are found in the urine
since cystine is lease soluble of dibasic amino acids it can form kidney stones
Type I: SLC3A1
Type II and III: SLC7A9
Code for heaby and light chains of brush border amino acid tansporter b
less transport, less aa recovered, mor in urine
*kidney cells can occur intracellularly if defective transporter for lysosomes
