AMINOACIDOPATHIES – CLASSIFICATION AND DIAGNOSIS : AMINOACIDOPATHIES – CLASSIFICATION AND DIAGNOSIS Dr. Hariharan, II yr MD biochemistry
15.09.2010 Moderator - Dr.Ragavendran,
Professor,
Dept of pediatrics
Co-ordinator- Dr. Ashok kumar, MD, DLO, Assistant Professor,
Dept of Biochemistry
History : History 1908- Garrod – alkaptonuria, benign pentosuria, albinism, cystinuria
Følling’s -phenylketonuria (PKU) in 1934
Harry Harris-1955-starch gel electrophoresis-demonstrated of a large number of protein polymorphisms in humans
discovery of PKU sparked the search for other clinically significant inborn errors of metabolism> 500 disorders
What can go wrong? : A A B C D negative E F Apoenzyme + cofactor What can go wrong?
Incidence of aminoacidurias : Incidence of aminoacidurias
Inheritance : Inheritance
Urea cycle defects : Urea cycle defects NH3 + H20 + CO2 Carbamoyl phosphate Hyperammonemia I Hyperammonemia II OTC Urea citrullinemia Argino succinic aciduria
Branched chain aminoacidurias : Branched chain aminoacidurias Isovaleryl coA dehydrogenase Alpha ketoacid dehydrogenase
Homocystinurias : Homocystinurias Homocystinuria 1 Cystathionine Homocystinuria 3 Homocystinuria 2 N5-N10 MTHF transferase MTHFR
Phenylalanine and tyrosine : Phenylalanine and tyrosine Tyrosinemia 2 Tyrosinemia 1 Alkaptonuria PKU hydroxylase Amino transferase Hydrolase
Laboratory investigation : Laboratory investigation Blood
Electrolytes, glucose, ammonia
URINE-
Ferric chloride test- alkaptonuria
Cyanide nitroprusside -S-
DNPH-MSUD
Benedict’s test -alkaptonuria
Thin layer chromatography
Tandem mass spectrometry
Confirmatory tests : Confirmatory tests PKU- plasma phenyl alanine levels, urinary metabolites
Tyrosinemias-plasma tyrosine levels, urine- succinyl acetone
Homocystinurias- increased plasma methionine & homocysteine. Low cystine
MSUD- increased leucine, isoleucine, valine
Urea cycle defects- ammonia, glutamine, alanine, other aminoacids
Collection of urine sample : Collection of urine sample
Screening in newborn : Screening in newborn Guthrie’s test- earliest
Various procedures in varying countries
References : References Vasudevan- textbook of biochemistry
A clinical guide to inherited metabolic disorders- Clarke
Pubmed.com
Wikipedia.org
Slide 18: Thank you