5&6 - Inborn Errors of Metabolism

Question 1

2 main presenting signs of inborn error of metabolism

Answer 1

lethargy and poor feeding

Question 2

def enzyme in PKU

Answer 2

phenylalanine hydroxylase

Question 3

problems caused by elevated Phe and dec Tyr in PKU

Answer 3

dec transport of neutral AAs into brain > dec cerebral protein synth
inhib of cholesterol synth
phe fibrils

dec Tyr > dec synth of NTs

Question 4

drug to help treat PKU (does not replace dietary restriction)

Answer 4

sapropterin (Kuvan) - cofactor that can inc PAH enzyme activity, variable results

Question 5

5 basic d/o checked for in newborn screening

Answer 5

PKU
galactosemia
congenital hypothyroid
hemoglobinopathies
congenital adrenal hyperplasia

Question 6

MC urea cycle disorder and inheritance

Answer 6

ornithine transcarbomylase deficiency - X linked

Question 7

why is OTCD not screened for in newborn screen?

Answer 7

present in neonatal period as catastrophic illness due to buildup of ammonia - happens before screen results would be back

Question 8

lab findings in OTCD

Answer 8

hyperammonemia
low serum citrulline
elevated urine orotic acid

Question 9

tx of OTCD

Answer 9

acute - dec ammonia w/ hemodialysis, nitrogen scavengers; prevent muscle breakdown w/ dextrose and insulin, IV arginine
outpatient - protein restricted diet, oral nitrogen scavengers, oral citrulline
liver transplant can “cure” but there are risks obviously

Question 10

Gaucher dz - category, what is wrong, inheritance

Answer 10

lysosomal storage
def of acid-beta glucosidase
AR

Question 11

Gaucher dz - types

Answer 11

type 1 - affects young adults, no nervous system involvement, can be mild to severe but still have some enzyme activity
type 2 - infants, early CNS probs, die in infancy
type 3 - children/young adults, later onset of CNS probs, becomes severe over time

Question 12

tissues affected by Gaucher dz

Answer 12

bone marrow, liver, bone, lung (alveolar macrophages), spleen

Question 13

Hurler spectrum - type of d/o, inheritance, cause

Answer 13

lysosomal storage (GAGs)
AR
def of alpha L iduronidase - needed to degrade heparan and dermatan sulfate

Question 14

hurler syndrome course

Answer 14

nl at birth
over first year - coarse facial features develop, hepatosplenomegaly, umbilical/inguinal hernia, skeletal abnlties
2nd yr - developmental delay, resp infxns, enlarging head, HF, hernias, slowed growth, loss of vision and hearing
lifespan <10yrs

Question 15

spectrum of Hurler syndrome

Answer 15

Scheie > Hurler-Schie > Hurler

least to most severe

Question 16

tx of hurler syndrome

Answer 16

aldurazyme - enzyme replacement

Question 17

Hunter synd - type of d/o, inheritance, cause

Answer 17

lysosomal storage (GAG)
XL
def of iduronate-2-sulfate sulfatase
needed for deg of heparan and dermatan sulfate

Question 18

presentation / course of Hunter synd

Answer 18

onsets at age 2-4, lifespan depends on severity
macrocephaly, short stature, coarse facial features, thick skin, retina problems, progressive hearing loss, URTIs, PNA, heart dz, hepatosplenomegaly, hernias, CNS involvement, joint stiffness

Question 19

tx of Hunter synd

Answer 19

idursulfase - recombinant DNA in human cell line

Question 20

Pompe dz - type of d/o, inheritance, cause

Answer 20

lysosomal storage
AR
lysosomal acid maltase (alpha 1 4 glucosidase) def > buildup of glycogen

Question 21

presentation of Pompe dz

Answer 21

generalized hypotonia, myopathic face, macroglossia, cardiomyopathy, short PR / high amp QRS (hypertrophic cardiomyopathy), vacuolated lymphocytes

Question 22

diff btwn infantile and later onset Pompe dzs

Answer 22

infantile - severe cardiomyopathy, die w/in 2 yrs from cardiac insufficiency
juvenile - more skeletal myopathy > resp failure, progressive weakness, usually spares heart. death in 2nd-3rd decade
adult - progressive proximal weakness w/ diaphragmatic involvement, dilated arteriopathy, carotid art dissection, heart and liver not usually involved

Question 23

tx of Pompe dz

Answer 23

a1glucosidase A - recombinant DNA