Inborn Errors of Metabolism

Question 1

phenylketonuria

Answer 1

AR
def: phenylalanine hydroxylase
elevated serum phenylalanine
blond, blue eyed vomiting pt w/ musty odor --> seizures
atopic-like derm

Question 2

homocystinuria

Answer 2

AR
def: cystathionine B-synthase –>
increased methionine & homocysteine, decreased cysteine
MR & charlie chaplin gait
ectopia lentis - lens displaced downward (marfans displaced upwards)
malar flush, livedo reticularis - vasculopathy

Question 3

alkaptonuria (ochronosis)

Answer 3

AR
def: homogentisate 1,2-dioxygenase
histopath: yellow/brown pigment in dermis (banana)
brown pigmentation ears, sclera, axilla, eccrine openings, cerumen

Question 4

trimethylaminuria

Answer 4

fish odor syndrome
mutation FMO3 gene
accumulation trimethylamine in sweat & urine

Question 5

type I hyperlipidemia

Answer 5

eruptive, tendinous, xanthelasmas
high TGC, chylomicrons. low LDL, HDL
GI: acute abd, pancreatitis, hepatosplenomegaly

Question 6

type II hyperlipidemia

Answer 6

planar, tendinous, tuberous
generalized atherosclerosis
arcus cornea
high TGC, LD. low HDL

Question 7

alagille disease

Answer 7

AD
mutation: Jagged 1
hyperlipidemia, xanthomas
congenital intrahepatic biliary hypoplasia
unusual facies

Question 7

alagille disease

Answer 7

AD
mutation: Jagged 1
hyperlipidemia, xanthomas
congenital intrahepatic biliary hypoplasia
unusual facies

Question 8

sitosterolemia

Answer 8

AR
mutation ABSG5 (encoding sterolin-1) or ABCG8 (encoding sterolin-2)
tuberous & tendinous xanthomas, premature cardiovascular ds

Question 8

sitosterolemia

Answer 8

AR
mutation ABSG5 (encoding sterolin-1) or ABCG8 (encoding sterolin-2)
tuberous & tendinous xanthomas, premature cardiovascular ds

Question 9

cerebrotendinous xanthomatosis

Answer 9

AR
sterol 27-hydroxylase mutation
tendinous xanthomas, MR, cataracts

Question 9

cerebrotendinous xanthomatosis

Answer 9

AR
sterol 27-hydroxylase mutation
tendinous xanthomas, MR, cataracts

Question 10

tangier disease

Answer 10

aka familial HDL deficiency
AR
mutation in ATP-binding cassette (ABC1)
hypocholesterolemia, absent HDL, decreased plasma ApoA-1
tonsil enlargement, lipid deposit in skin

Question 10

tangier disease

Answer 10

aka familial HDL deficiency
AR
mutation in ATP-binding cassette (ABC1)
hypocholesterolemia, absent HDL, decreased plasma ApoA-1
tonsil enlargement, lipid deposit in skin

Question 11

Hurler Syndrome

Answer 11

mucopolysaccharidosis
AR
defect: alpha-L iduronidase (can't degrade dermatan sulfate and heparan sulfate)
death before 10 yo - cardiac/resp
MR, taught skin, clouding cornea

Question 12

hunter syndrome

Answer 12

mucopolysaccharidosis
XLR
iduronate-2-sulfatase
no corneal clouding (see to hunt)
firm flesh colored-ivory white papules and nodues of scapula and posterior axillary lines (hunter pulling arrows from quiver)

Question 13

acromegaly presentation

Answer 13

cutis verticis gyrata

hypertrichosis & hyperpigmentation

Question 14

cutaneous findings gigantism

Answer 14

enlarged hands/feet
coarse facies
puffy eyebrows

Question 15

gonadal dysgenesis cutaneous findings

Answer 15

severe nail hypoplasia (pathognomonic)
thin, markedly hyper convex nails (pathognomonic)
cutis verticis gyrata
webbed neck

Question 16

addison’s disease cutaneous findings

Answer 16

hyperpigmented longitudinal nail streaks
hyperpigmentation
blue-black gums
assoc w/ vitiligo

Question 17

leprechaunism

Answer 17

AR - insulin receptor gene
absent subcu fat
acanthosis nigricans, hypertrichosis, hyperpigmentation
elfin facies, lg genitalia

Question 18

rabson-mendenhall syndrome

Answer 18

AR
insulin receptor gene
acanthosis nigricans, coarse facies, gingival hyperplasia

Question 19

Berardinelli-Seip

Answer 19

congenital generalized lipodystrophies
AGPAT2 gene, seipin gene
lAN, hyperhidrosis

Question 20

pseudohypoparathyroidism

Answer 20

AD
LOF mutation of GNAS1
round face, short stature, brachydactyly (knuckle, knuckle, dimple, dimple)
calcinosis cutis

Question 21

mccune albright syndrome

Answer 21

GNAS1 gene mutation | cafe-au-lait coast of Maine

Question 22

Carney complex

Answer 22

``` AD PRKARIA gene (park car..ney) lentigines pigmentation of conjunctiva melanotic schwanomas adrenal, pituitary, testicular, thyroid cancers ```

Question 23

MEN-1

Answer 23

wermer's ds AD parathyroid hyperplasia, pituitary adenomas cutaneous - 'waste basket'

Question 24

MEN-2a

Answer 24

AD ret proto sipple syndrome medullary carcinoma of thyroid, pheo, parathyroid hyperplasia (MPP) lichen amyloid (a)

Question 25

MEN-2b

Answer 25

``` medullary carcinoma of thyroid, pheo, neuromas (MPN) buccal neuromas (b), marfanoid, cafe-au-lait ```

Question 26

Carney complex

Answer 26

``` AD lentigines pigmentation of conjunctiva melanotic schwanomas adrenal, pituitary, testicular, thyroid cancers ```