Metabolic Flashcards
What are the 8 major classifications of metabolic disorders?
and what is one example from each class
- Organic acid metabolism: MethylMalonic Acidaemia, proprionic, isovaleric, MSUD
- Fatty Acid Metabolism:MCAD, VLFCAD
- Amino Acid Metabolism: PKU, Homocysteinuria
- Lysosomal Storage disorders: Mucopolysaccaridoses (MPS1-3; Hurler, Hunter and Scheie)
- Carbohydrate metabolism disorders (DKA)
- Urea cycle disorders (OTC - Ornithine carbamylase deficiency)
- Mitochondrial disorders (MELAS)
- Peroxisomal disorders (Zelwegger, adrenoleukodystrophies)
what are the metabolic conditions tested on neonatal screening?
PKU Organic acid metabolic disorders Fatty Acid metabolic disorders amino acid metabolic disorders Galactosaemia
What are the major manifestations of tyrosinaemia?
- acute hepatic crisis: raised transaminases
- Peripheral Neuropahy
- Renal involvement: fanconi like (with hyperphosphaturia, hypophosphataemia, nagma, vit d resistant rickets)
What is the enzyme deficiency in Tyrosinaemia?
fumarylacetoacetate hydrolase
What are the biomarkers for Tyrosinaemia?
elevated levels of succinylacetone in urine or blood and elevated AFP
How is Tyronsinaemia treated?
Restricting phenylalanine and tyroseine can slow progression
The treatment of choice is nitisinone, which inhibits tyrosine degradation at 4-HPPD
What are the major manifestations of Tyrosinaemia Type 2?
- occular: excessive tearing, redness, pain, and photophobia; tyrosine deposits in the eye - corneal lesions.
- painful, nonpruritic hyperkeratotic plaques on the soles, palms, and fingertips. Intellectual disability, which occurs in approximately 50% of patients, is usually mild to moderate.
What are the Amino acid metabolic disorders?
- Phenylalanine
- tyrosine
- Methionine
- Cysteine
- Typtophan
- Valine, Leucine, Isoleucine
- Glycine
- Serine
- Proline
- histadine
11: glutamic acid
12: Lysine - Aspartic acid
What are the causes of albinism?
OCULOCUTANEOUS ALBINISM (OCA)
OCA1 (tyrosinase deficient) TYR 11q14-q21
OCA1A (severe deficiency) TYR 11q14-q21
OCA1B (mild deficiency)* TYR 11q14-q21
OCA2 (tyrosinase positive)† OCA2 15q12-q13
OCA3 (Rufous, red OCA) TYRP1‡ 9p23
OCA4 SLC45A2 5p13.3
Hermansky-Pudlak syndrome HPS1-9 Different chromosomes
Chédiak-Higashi syndrome LYST 1q42.1
OCULAR ALBINISM (OA) OA1 (Nettleship-Falls type)
OA Xp22.3
LOCALIZED ALBINISM Piebaldism KIT 4q12
Waardenburg syndrome (WS1-WS4)
what are the clinical manifestations of homocysteinuria?
how is it inherited?
Autosomal Recessive
- subluxation of the ocular lens (ectopia lentis)
- progressive intelectual disability
- skeletal abnormalities: they are usually tall and thin, with elongated limbs and arachno- dactyly.
what is the treatment for homocysteinuria
Treatment with high doses of vitamin B6 (200-1,000 mg/24 hr) causes dramatic improvement in most patients who are responsive to this therapy. HCU anamix
What are the clinical manifestations of wardenburg and what is the gene associated?
- white forelock
2.Lateral displacement of inner canthi of the eyes, - broad nasal bridge, heterochromia of irides
- sensorineural deafness.
Autosomal Dominant mutation of the PAX3 gene
What is the biochemical marker for homocysteinuria?
- megaloblastic anemia,
- homocystinuria, and
- hypomethioninemia.
The presence of megaloblastic anemia differentiates these defects from homocystinuria due to methylenetetrahydrofolate reductase deficiency
What are the disorders of medium branch chain amino acids?
MSUD (Maple Syrup urine disease)
Progressive encephalopathy from 3rd-5th days of life, lethargy, feeding difficulties, somnolence, cerebral oedema, coma
E1a/BCKDHA/B, E2/DBT, E3/DLD
glucos+insulin IV; enhance protein anabolism
Long term: diet (plasma leu/val/ile) Thiamine
Disorders of branched chain organic acids?
Valine/Isoleucine/Leucine
- metabolised predominantly in the muscle and kidney - important substrates of gluconeogenesis
1. Propionic aciduria (PA)
2. Methylmalonic aciduria (MMA)
3. isovaleric aciduria (IVA)
4. Glutaric aciduria type 1 (GA1)
