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• Pharmacological chaperones as a potential therapeutic option in methylmalonic aci-
Most relevant
duria cblB type. JorGe-FinniGan a, brasil s, underhauG J, ruíz-sala P, Merinero b, baner-
scientific r, d lr, u M, M a, P b. Humman Molecular Genetics (2013)
Jee esViatGarteartínezérez
articles
22(18):3680-9.

• A novel regulatory defect in the Branched-Chain Alpha-ketoacid dehydrogenase

complex due to a mutation in the PPM1k Gene causes a mild variant phenotype of
maple Syrup Urine disease. oyarzabal a, Martínez-Pardo M, Merinero b, naVarrete r

desViat lr, uGarte M, rodríGuez-PoMbo P. Human Mutation (2013) 34(2): 355-362.

• Clinical Biochemical and molecular studies in pyridoxine-dependent epilepsy. anti-
sense therapy as possible new therapeutic option. b P, l G G-
elénérezuisonzálezutié
rrez-solana, alFonso Verdú, beGoña Merinero, Patricia yuste-checa, Pedro ruiz-sala, rocio
c, a J, l l M, o c, M á r, M s M,
alVonilalanauraóPezarínscaraMPosarianGelesuizartaaniGuel
Maria Vázquez, MarGarita castro, isaac Ferrer, rosa naVarrete, lourdes ruiz desViat, Pablo
l, M u c P-c. Epilepsia (2013) 54(2) 239-248.
aPunzinaaGdalenaGarteand eliaérezerdá

• A novel congenital disorder of glycosylation type without central nervous system in-
volvement caused by mutations in the phosphoglucomutase 1 gene. Pérez b, Medrano

c, ecay MJ, ruiz-sala P, Martínez-Pardo M, uGarte M, Pérez-cerdá c. J Inherit Metab Dis.
(2013) 36(3):535-42.

• Functional characterization of novel genotypes and cellular oxidative stress studies

in propionic acidemia. GalleGo-Villar l, Pérez-cerdá c, Pérez b, abia d, uGarte M, ri-
e, d lr. J Inherit Metab Dis. (2013) 36(5):731-40.
chard esViat

Our work is focused on the biochemical and genetic diagnosis of inherited meta-
Highlights
bolic diseases and also in the research of their molecular basis. In the last year we

have expanded the metabolomics (quantification of vitamins, sugars and mucopo-
lysaccharides) and enzymatic (CBS and LCHAD) analysis to detect of a number of

new metabolic disorders such as vitamin disorders, glycogen storage and galacto-
semia disorders and lysosomal disorders.

We have generated a proof-of-concept to use the next generation sequencing in the

clinical practice to perform the differential diagnosis of hyperphenylalaninemias.
Additionally we have defined the mutational spectrum of piridoxine-dependent epi-

lepsy in our country and we have identified for first time mutations in the PPM1K
gene encoded for the phosphatase which regulates the BCKDH complex. Finally we

have identified mutations in the PGM1 gene in a patient with congenital disorder of

glycosylation (CDG) connecting the CDG with the glycogenosis storage disorders.

Regarding the research in new therapies we have extensively analysed the effect
of mutants on the splicing and folding processes of genes and protein respectively,

describing several new molecular targets for therapeutic intervention, in the field
of what is known as personalized genetic medicine.

The group has developed a gene specific antisense RNA-based therapy for splicing 13
20
defects in a number of IMD. We are also working on the secondary mitochondrial T
dysfunction present in organic acidurias defects and we have postulated that ROS OR
P
could be a phenotypic modifier in these disorders and also a new therapeutic target RE
L
to treat with antioxidants. We have reported the proof-of concept for application of A
pharmacological chaperones in the treatment of methylmalonica aciduria cblB type.
NU
N
A high-throughput screening from a large drug library has been applied and several A
R /
hits have identified, one of them patented, which in combination with B12 are able E
to improve the stability and activity the mitochondrial protein adenosylcobalamin ER
B
transferase in a therapeutic range. Also we have demonstrated that is able to reach CI
tissue-disease organs such as brain and liver.

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