Genetics of Metabolic Bone Disease (t1.3a)

Question 1

X-linked hypophosphatemic rickets

Answer 1

Acellular endopeptidase: Vitamin D-resistant rickets

Rickets
Short stature
Impaired renal phosphate reabsorption and vitamin D metabolism

Question 2

Hypophosphatasia

Answer 2

Alkaline phosphatase gene: Generalized impairment of skeletal mineralization

Rickets
Bow leg
loss of teeth
short stature

Question 3

Familial osteolysis

Answer 3

OPGL, Rankl (osteoprotegrerin, receptor activator for nuclear factor kB ligand): Idiopathic multicentric osteolysis

facies - slender nose, maxillary hypoplasia, micrognathia
rheumatoid arthritis like hand deformities

Question 4

Mucopolysaccharidosis type I (MPSI)

Answer 4

alpha-L-iduronidase deficiency: lysosomal enzymes for breaking glycosaminoglycans

Hunter syndrome - progressive cellular damage that affects the development of neurologic and musculoskeletal systme
short stature
bone dysplasia

Question 5

Mucopolysaccharidosis type II (MPSII)

Answer 5

Iduronate sulfatase deviciency - X-linked recessive

Hunter syndrome - mild to moderate features of MPS

Question 6

Mucopolysaccharidosis type III (MPSIII)

Answer 6

IIIa) Heparan N-sulfatase
IIIb) N-acetylglucosaminidase 6-sulfatase
IIIc) acetyl-coenzymeA:alpha-glucosaminide-N-acetyltransferase
IIId) N-acetylglucosamine 6-sulfatase

Sanfilippo syndrome- severe neurologic syndrome with mild progressive musculoskeletal syndrome

Question 7

Mucopolysaccharidosis type IV (MPSIV)

Answer 7

IVa) N-acetylgalactosamine 6-sulfatase
IVb) beta-galactosidase

deficiency of lysosomal enzymes for breaking down keratin sulfate

Morquio syndrome: bell-shaped chest, spine anomalyh, short long bones, dysplasia of hip, knee, ankle, wrist
Odontoid hypoplasia