5&6 - Inborn Errors of Metabolism Flashcards
2 main presenting signs of inborn error of metabolism
lethargy and poor feeding
def enzyme in PKU
phenylalanine hydroxylase
problems caused by elevated Phe and dec Tyr in PKU
dec transport of neutral AAs into brain > dec cerebral protein synth
inhib of cholesterol synth
phe fibrils
dec Tyr > dec synth of NTs
drug to help treat PKU (does not replace dietary restriction)
sapropterin (Kuvan) - cofactor that can inc PAH enzyme activity, variable results
5 basic d/o checked for in newborn screening
PKU galactosemia congenital hypothyroid hemoglobinopathies congenital adrenal hyperplasia
MC urea cycle disorder and inheritance
ornithine transcarbomylase deficiency - X linked
why is OTCD not screened for in newborn screen?
present in neonatal period as catastrophic illness due to buildup of ammonia - happens before screen results would be back
lab findings in OTCD
hyperammonemia
low serum citrulline
elevated urine orotic acid
tx of OTCD
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
Gaucher dz - category, what is wrong, inheritance
lysosomal storage
def of acid-beta glucosidase
AR
Gaucher dz - types
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
tissues affected by Gaucher dz
bone marrow, liver, bone, lung (alveolar macrophages), spleen
Hurler spectrum - type of d/o, inheritance, cause
lysosomal storage (GAGs) AR def of alpha L iduronidase - needed to degrade heparan and dermatan sulfate
hurler syndrome course
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
spectrum of Hurler syndrome
Scheie > Hurler-Schie > Hurler
least to most severe
tx of hurler syndrome
aldurazyme - enzyme replacement
Hunter synd - type of d/o, inheritance, cause
lysosomal storage (GAG)
XL
def of iduronate-2-sulfate sulfatase
needed for deg of heparan and dermatan sulfate
presentation / course of Hunter synd
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
tx of Hunter synd
idursulfase - recombinant DNA in human cell line
Pompe dz - type of d/o, inheritance, cause
lysosomal storage
AR
lysosomal acid maltase (alpha 1 4 glucosidase) def > buildup of glycogen
presentation of Pompe dz
generalized hypotonia, myopathic face, macroglossia, cardiomyopathy, short PR / high amp QRS (hypertrophic cardiomyopathy), vacuolated lymphocytes
diff btwn infantile and later onset Pompe dzs
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
tx of Pompe dz
a1glucosidase A - recombinant DNA
