Galactosemia (Galactose-1-phosphate uridyl transferase [GALT] deficiency

defective metabolism of galactose (a breakdown product of lactose)

lab --> Both Direct and indirect bilirrubin levels may be elevated

Achoncroplasia --> Most common cause of Dwarfism

most common skeletal dysplasia; AD inheritance; Full penetrance
defective endochondral ossification and growth disorders of the long bones
due to activating mutation of the fibroblast growth factor receptor 3 gene (FGFR-3)
located in chromosome 4

FGFR-3 is a Tyrosine Kinase Receptor (Mutation leads to gain of function)

FGFR-3 gene activating mutation --> Inhibited chondrocyte proliferation and
dysfunctional endochondral ossification of the long bones
Characterized by: Trident hands, short extremities (Rhizomelia),
Narrow trunk, Macrocephaly, fontal bossing and flattened nose, Spinal Canal
stenosis
Complications --> Inc risk CV disease; Obesity

Defective type I collagen synthesis --> osteogenesis imperfecta (OI)

Blue sclerae + Triangular facial appearance + recurrent fractures -->bone fragility
Deafness + Dentiogenesis imperfecta + Tendon instability

Early closure of the epiphyseal growth plates -->precocious puberty

Increased activity of osteoclasts -->results in demineralization of bone tissue,

as in osteoporosis.

Inactivation of fibroblast growth factor receptor 1 (FGFR1) -> Kallmann syndrome

Disproportionaly long arms + Delayed puberty and Anosmia

Growth hormone deficiency -->proportionate (not disproportionate) short stature

+ muscular atrophy + Infantile voice + Sparse hair growth + delayed puberty

Osteo-blasts differentiate from mesenchymal stem cells in the periosteum

the First step of bone formation is osteoblastic production of OSTEOID

deposition of Calcium Phosphate into Osteoid wich is converted to Hydroxyapatite
OSteoid --> Proteinaceous Matrix composed of most type I Collagen

Vitamin K deficiency
Associated with Crohn's Disease/Cystic Fibrosis --> Fat soluble vitamin
deficiencuies
Prolonged Antibiotic Use
Lab: ↑ PT and PTT
Normal Bleeding time
Can cause Neonatal Hemorrhage
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Thiamine (B1)
Active (coenzyme) form --> Thiamine pyrophosphate (TPP)
Primary function --> Decarboxylation of Alpha-Keto acids (Carbohydrate metabolism)

Thiamine deficiency (Most common in alcoholics)

- Wernicke & Korsakoff Syndrome
(ataxia, nystagmus, ophthalmoplegia) / (confabulation, psychosis)
--> Glucose (Dextrose)infusion before thiamine depletes ATP
(ATP depletion in vitamin B1 (thiamine) deficiency is worsened by glucose infusion)

Dry Beriberi --> Peripheral Polyneuropathy (Sensory and motor impariments)

Wet Beriberi --> dilated Cardiomyopathy/High-output Congestive Heart Failure
+ peripheral edema + Polyneuropathy