Hematologic/immunologic disorders/multiple congenital anomalies

Question 1

results from half normal activity of hydroxymethylbilane synthase (HMBS)

Answer 1

Acute intermittent porphyria

aka Porphobillinogen deaminase deficiency

Triad: hyponatremia, abdominal pain, seizure

colorless urine (when light exposed turns dark)

Tx: IV heme (Panhematin)

Question 2

What substance is increased during acute attackes of acute intermittent porphyria

Answer 2

increase in urine (porphobilinogen)

PBG and urine delta-amonolevulinic acid (ALA)

Question 3

loss or dysfunction of all 4 alpha thal alleles, hydrops fetalis, severe hypochromic anaemia

Answer 3

HB Bart

Question 4

F5 G to A substitution at nt 1691 (100%)

Answer 4

Factor V Leiden thrombophilia

The G>A substitution affects an APC cleavage site and the mutant factor V
Leiden is inactivated 10x more slowly and persists longer in circulation-> inc. thrombin generation

Question 5

Severe cases of Factor VIII deficiency 45% caused by this type of mutation

Answer 5

Hemophillia A: FactorVIII deficiency

XLR

• F8* intron 22 gene inversion (45%)
• F8* intron 1 gene inversion in (3%)

Question 6

Target mutation testing (60% C282Y/C282Y ; 3% C282Y/ H63D)

Answer 6

HFE- associated hereditary hemochromotosis

Question 7

recurrent febrile episodes with fever

peritonitis

erysipelas-like erythema

synovitis or pleuritis

AA type amyloidosis

possible treatment?

Answer 7

Familial Mediterranean Fever

MEFV : AR

Tx: Cholchicine: decrease inflammatory attacks and amyloid desposition

Question 8

recurrent infections in males in the first two years of life

S pneumonia and H influenzae most common infections

marked decrease in all immunoglobulins

abcent B cells (CD 19+)

Answer 8

X-linked agammaglobulinemia

(Bruton’s agammaglobulinemia)

• BTK*
• XLR*

Question 9

shawl scrotum

hypertelorism

short stature

cryptorchidism

intellectual disability

disorder and inheritance?

Answer 9

Aarskogg Syndrome

XLR FGD1

milder manifestation in females

Question 10

maternal virillization during pregnancy with an affected fetus

cranosynostosis

ambiguous genetalia

skeletal abnormalities

may be picked up on newborn screen with elevated 17-OH progesterone

Answer 10

Antley-Bixler Syndrome

PORD : AR

cytochrome P450 reductase def.

low maternal e3 during pregnancy

prenatal testing: maternal urinary steroid profile

Question 11

cone-rod dystrophy

post-axial polydactyly

male hypoganadotropic hypogonadism

GU abnormalities

renal abnormalities

Answer 11

Bardet-Biedel

BBS1 and BBS10

AR

defects in cillia or intraflagellar transport

Question 12

malformation of the outer inner and middle ear

hearing loss

brachail fistulea and cysts

renal malformations

Answer 12

brachio-oto-renal syndrome

EYA1 SIX1 SIX5

Autosomal dominant

Question 13

eye coloboma

heart defects

choanal atresia

retardation of growth/ ID

GU abnormalities

Ear anomalies

Answer 13

CHARGE syndrome

CHD7

Autosomal dominant

Question 14

sever to profound ID

Short Stature <3% in height

stimulus induced drop episodes

self-injury

short fleshy hands

large mouth , everted bottom lip

large ears

Answer 14

Coffin-Lowry Syndrome

XLD

RPS6KA3

Question 15

macrocephaly

preaxial polydactly

syndactyly

allelic with pallister-hall syndrome

Answer 15

Greig cephalopolysyndactyly

GLI3

7p13

AD

haploinsufficiency

involved in regulation of SHH pathway

Question 16

hypotonia in infancy

jerky eye movments

oculomotor apraxia

tacypnea and or apnea

molor tooth sign (cerebellar vermis hypoplasia) on MRI

pigment retinopathy and renal disease

rare hepatic fibrosis

Answer 16

Joubert Syndrome

AR

Question 17

elongated PF

everted inner lower eyelid

prominant arched eyebows

short collumela

large cupped ears

long eyelashes

vertabral anomalies

Answer 17

Kabuki syndrome

KMT2D (60%)

Question 18

most common terminal deletion syndrome

hypotonia, growth delay ID

cleft L/P

majority are matternally derived

Answer 18

Monosomy 1p36 deletion syndrome

Question 19

broad deviated thumbs and first toes

beaked nose

short stature (normal prenatal growth)

intellectual disability

low hanging columella

high palate and grimacing smile

tumors

Answer 19

Rubinstein-Taybi Syndrome

CREBBP, EP300

CREBBP abnormal gene product: interfere with acytelation of histones; also a tumor suppresor

AD

Question 20

infantile hypotonia

feeding difficulty and FTT

short stature

stereotypical behaviour : “self-hug” and “lick and flip”

sleep problems

brachycephaly, hypotelorism, square face everted upper lip, deep set eyes and prognathism

Answer 20

Smith-Magenis Syndrome

17p11.2 deletion (includes the RAI1 gene)

AD

Question 21

greek warrior helmet appearence (broad nasal bridge that continues to the forehead, high forehead with prominant glabella)

pre and post natal growth def.

IgA deficiency

Pulmonary valve stenosis

absence seizures

Answer 21

Wolf-Hirschorn Syndrome

4p minus (Monosomy 4p)

87% de novo

valproate responsive absence seizures

Question 22

oversensitive to light

blisters on skin

excess urioporphyrin and hepatocarboxyporphyrin

Answer 22

Porphoryia Cutanea Tarda

UROD- Urophorphyrinogen decarboxylase deficiency

Type 2- AD result in 50% reduction of UROD

TX: Hydroxychloroquinones

Triggers: HIV, iron , led Hep C, alcohol