Maple Syrup Urine Disease 2012

Summary

place summary in here

Biochemical disease mechanism

MSUD affects a protein called branched-chain alpha-keto acid dehydrogenase complex (BCKDHC), which is involved in the degradation of branched amino acids (Val, Leu, Ile). BCKDHC consists of four subunits:

subunit	name	chromosomal gene location	MSUD-type
BCKDHA	Branched chain keto acid dehydrogenase E1, alpha polypeptide	19q13.1-q13.2	1a
BCKDHB	branched chain keto acid dehydrogenase E1, beta polypeptide	6q14.1	1b
DBT	Dihydrolipoamide branched chain transacylase E2	1p31	2
DLD	dihydrolipoamide dehydrogenase	7q31-q32	3

Reference sequence

Reference sequence (uniprot)

Mutated sequence

• Nonsense/missense mutatet sequence BCKDHA

>sp|P12694|ODBA_HUMAN 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial OS=Homo sapiens GN=BCKDHA PE=1 SV=2
MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAE
FIDKLEFIQPNVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILY
ESQRQGRISFYMTNYGEEGTHVGSAAALDNMNLVFGQYWEAGVLMNQDYPLELFMAQCYG
NISDLGKGRKMPVHYGCKERHFVTISSPLATQTPQVVGAAYAAKRANANRVVICYFGEGA
ASEGDAHASFNFTATLEYPIIFFWWNSGYAISTPTSEQYRGDDIPA|GPRYGIMSIC/HVD
SNAVFAVYNARKEA|RRAVAENQPFLTKTMTYRIGHHSTSDDSSAYHSVDEVNYWDKQDH
PISWLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLCSDMH/CQEMPA
QLRKQQESLARHLQTYGEHNPLDHFDK

• Nonsense/missense mutatet sequence BCKDHB

>sp|P21953|ODBB_HUMAN 2-oxoisovalerate dehydrogenase subunit beta, mitochondrial OS=Homo sapiens GN=BCKDHB PE=1 SV=2 MAVVAAAAGWLLRLRAAGAEGHWRRLPGAGLARGFLHPAATVEDAAQRRQVAHFTFQPDP EPREYGQTQKMNLFQSVTSALDNSLAKDPTAVIFGEDVAFGGVFRCTVGL|DKYGKDRGF NTLLCEQGIGGFGIRIVVTGATAIAEIQFADYIFPAFDKIVN|AAKYH/CYRSWDLFYCGS LTIPSPWGCDGHGALYHSQSAEAFFAR/YCPGIKVVKPGSPFQARGLLLSCIEDKNPCIFF EP|ILHRAAAEEAPIEPYNIPLSQAEVI|EGSDVTLVACSTQVHAI|EVASMAKEKLGVS CEVIDLRTIIPWDVDTICKSVIKTG|LLISHEAPLTGGFALKISSTVQEECFLNLEALIS RVCGYDTPFPHIF|PFYIPDKWKC|DALRKMINY

• Nonsense/missense mutatet sequence DBT (leading to type 1)

>sp|P11182|ODB2_HUMAN Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial OS=Homo sapiens GN=DBT PE=1 SV=3 MAAVRMLRTWSRNAGKLICVRYFQTCGNVHVLKPNYVCFFGYPSFKYSHPHHFLKTTAAL RGQVVQFKLSDIGEGIREVTVKEWYVKEGDTVSQFDSMCEVQSDKASVTITSRYDGVIKK LYYNLDDIAYVRKPLVDTETEALKDSEEDVVETPAVSHDEHTHQEIKGRKTLATPAVRRL AMENNIKLSEVVG|GKDGRILKEDILNYLEKQTGAILPPSPKV|IMPPPPKPKDMTVPIL VSKPPVFTGKDKTEPIKGFQKATVKTMSAALKIPHCGYCDEIDLTELVKLREELKPIAFA RGIKLSSMPFFLNAASLGLLQFPILNASVDENCQNITYKASNNIGIAMDTEQGLIVPNVK NVQICSIFDIATELNRLQKLGSVSQLSTTGLTGGTFTPSNIGSIGGTFAKQVIMPPEVAI GALGSIKANPRFNQKGEVYKAQIMNMSWSDDRRVIDGATMSPFSNLWKSYLENPAFMLLD LK

• Nonsense/missense mutatet sequence DBT (leading to type 2)

• Nonsense/missense mutatet sequence DLT (leading to type 2)

>sp|P09622|DLDH_HUMAN Dihydrolipoyl dehydrogenase, mitochondrial OS=Homo sapiens GN=DLD PE=1 SV=2 MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKA AQLGFKTVCIEENETLGGTCLNVGCIPSKALLNNSHYYHMAHGTDFASRGIEMSEVRLNL DKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNIL IATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELCSVWQRLGADVT AVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGK AEVITCDVLLVCIGRRPFTKNLGLEELGIEVDPRGRIPVNTRFQTKIPNIYAIGDVVAGP MLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDI ARVCHAHLTLSEAFGEANLAASFGKSINF