Inborn Errors of Metabolism

Question 1

Cobalamin C disease

Answer 1

Defect in protein that converts Vit B12 in body

Question 2

PKU

Answer 2

PAH; AR
Most common IEM; 1 in 10,000
Defect in PAH enzyme/cofactor BH4 that coverts Phe to Tyr
“Classical PKU” (>1200umol/L) vs. “hyperphe” (<600 umol/L)
Epilepsy, ID, behavior problems, autistic features, Parkinsonian features, musty odor, eczema
If treated, still at risk for executive function defecits, ADHD, “fogginess”, learning impairment, fatigue, headaches, anxiety, depression, social struggles
Maternal PKU has teratogenic effects (similar to FAS)

Question 3

Maple syrup urine disease

Answer 3

AR; BCKDHA, BCKDHB, DBT
inability to break down BCAAs
1:185k
Ash Jew: 1:26k
Mennonite: 1:385

Question 4

Ornithine transcarbamylase (OTC) deficiency

Answer 4

OTC; X-linked
Urea cycle disorder; ammonia accumulates from lack of proper breakdown of proteins
Damages liver and nervous system
Neonatal-onset and late-onset forms
1 in 14k - 77k
Jesse Geisinger

Question 5

methylmalonic acidemia

Answer 5

AR; MMUT, MMAA, MMAB, MCEE, & one more

-different subtypes: severe infantile (MMUT) & partially deficient

Question 6

Fumurase Hydratase Deficiency

Answer 6

AR; FH gene
(AD is HLRCC renal cancer syndrome)
-LOF of tumor suppressor encoding fumurate hydratase, which is involved in the conversion of fumurate to L-malate in the tricarboxylic acid (Krebs) cycle, leading to increased fumurate levels