First half of biochem path

Question 1

I-cell disease (inclusion cell disease/mucolipidosis type II)

Answer 1

Lysosomal storage disorder
Defect in N-acetylglucosaminyl-1-phosphotransferase
Golgi fails to phosphorylate mannose residues so less mannose-6-phosphate
Proteins secreted extracellularly and not sent to lysosome as mannose usually does

Clinic: coarse facies, clouded corneas, joint restriction, high plasma levels of lysosomal enzymes

Fatal in childhood

Question 2

Zellweger syndrome

Answer 2

Peroxisomes normally catabolize v. long FA, branching FA, AA and EtOH
If defective, can’t make plasmalogens (phospholipids in myelin)

Hypotonia, seizures, hepatomegaly, early death

Question 3

Refsum disease

Answer 3

Peroxisomes normally catabolize v. long FA, branching FA, AA and EtOH
If defective, can’t make plasmalogens (phospholipids in myelin)

Scaly skin, ataxia, cataracts, night blindness, short 4th toe, epiphyseal dysplasia

Question 4

Kartagener syndrome

Answer 4

1˚ ciliary dyskinesia
Dynein arm defect, can’t move cilia

Decreased fertility, ectopic pregnancy, bronchiectasis, sinusitis, otitis, hearing loss, situs inversus

Question 5

Vascular type Ehler-Danlos syndrome

Answer 5

Type III Collagen defect
Organ or vessel rupture
Defective cleavage of C and N termini in forming tropocollagen outside the cell

Question 6

Classical type Ehler-Danlos syndrome

Answer 6

Defective cleavage of C and N termini in forming tropocollagen outside the cell
Type V collage defect

Question 7

Osteogenesis imperfecta

Answer 7

Type I collagen defect from quantitative or qualitative deficiency
Common, less procollagen made in cell
Fracture, blue sclera, tooth abnormalities, hearing loss

Qualitative defect is more severe

Question 8

Menkes disease

Answer 8

XLR defect in ATP7A (impaired Cu absorption and transport)
decreased lysyl oxidase activity on tropocollagen (Cu is a cofactor) less collagen

Brittle, kinky hair, growth retardation, hypotonia

Question 9

Marfan syndrome

Answer 9

Ch15 AD FBN1 gene
fibrillin normally forms a sheath around elastin

Tall, pectus carinatum, hypermobile joints, long limbs, cystic medial necrosis of aorta, aortic incompetence, dissecting aortic aneurysms, floppy mitral valve, subluxation of lenses (superotemporally)

Question 10

Prader-Willi syndrome

Answer 10

Ch15
Maternal imprinting with paternal mutation/deletion
OR maternal uniparental disomy

Hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia

Question 11

Angelman syndrome

Answer 11

Ch15
Paternal imprinting with maternal mutation/deletion
OR paternal uniparental disomy

Seizures, ataxia, inappropriate laughter, severe intellectual disability

Question 12

Pseudopseudohypoparathyroidism

Answer 12

Labs are normal
Paternally imprinted genes for PTH-R expressed throughout body except bone and kidney where maternal (work) are expressed, so you get the phenotype of hypoPTH, but the labs are normal

Question 13

Hypophosphatemic rickets

Answer 13

XLD; increased phosphate wasting at PCT; vitamin-D resistant

Presents like rickets

Question 14

MELAS

Answer 14

Mitochondrial inheritance
Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes

Biopsy: ragged red fibers

Question 15

CF

Answer 15

See chapter FA p56 (review in pulm/GI)

Question 16

DMD/BMD/myotonic dystrophy

Answer 16

FA p57; review in MSK

Question 17

Fragile X sydrome

Answer 17

XLD; TNR in 5’UTR of CGG (chin, giant gonads)
leads to hypermethylation and silencing of FMR1 gene

2nd most common inherited intellectual disability

Clinic: post-pubertal macroorchidism, long face, large jaw, large everted ears, autism, mitral valve prolapse

Question 18

Down syndrome

Answer 18

Trisomy 21
Intellectual disability, flat facies, prominant eipcanthal folds, single palmar crease, gap b/w 1st and 2nd toes, duodenal atresia, Hirschsprung dz, heart defect AVSD

Early onset AD, risk of ALL, AML

Maternal age a risk

Some due to Robertsonian translocation 14 and 21

1st tri: high bhCG
2nd tri: high bhCG; low AFP

Question 19

Edwards syndrome

Answer 19

trisomy 18
Prominent occiput, rocker-bottom feet, intellectual disability, nondisjunction, clenched fists, low set ears, micrognathia, heart defect
Death by 1y

1st tri: low bhCG
Quad: low bhCG/AFP

Question 20

Patau syndrome

Answer 20

Trisomy 13
Severe intellectual disability, rocker-bottom feet, microphthalmia, cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia, congenital heart defect
death by 1y
low bhCG

Question 21

Cri-du-chat syndrome

Answer 21

del5p

Microcephaly, intellectual disability, meowing, epicanthal folds, VSD

Question 22

Williams syndrome

Answer 22

del7q including elastin gene

Elvin facies, intellectual disability, hypercalcemia (Vit. D sensitivity), good verbal skills, friendly, CVdz

Question 23

DiGeorge syndrome

Answer 23

del22q11

Thymic, parathyroid and cardiac defects

Question 24

Velocardiofacial syndrome

Answer 24

palate, facial and cardiac defects

have PT and thymus