ssiem 2016 - asmn.re.it
TRANSCRIPT
SSIEM 2016
IN PILLOLE
Mitocondrio
Pearson syndromesideroblastic anemia exocrine pancreas dysfunction (steatorrhea)usually fatal in infancy
Kearns-Sayre syndrome (KSS) obligatory triad:1)Onset before age 20 years2)Pigmentary retinopathy FOO atypical "salt and pepper" retinopathy; ERG often reveals retinal dystrophy3) Progressive external ophthalmoplegia (PEO)
At least one of the following must also be present:Cardiac conduction blockCerebrospinal fluid protein concentration greater than 100 mg/dLCerebellar ataxia
PEOPtosisophthalmoplegia oropharyngeal weakness, variably severe proximal limb weakness
Mitochondrial DNA Deletion Syndromes
Oa 9 pz
5 KSS
NORMALE O POCO SIGNIFICATIVO
4 PMS
3 IDROSSIBUTIRRATO
2 METIL – 3 OH BUTIRRATO
NB AO NORMALI NON ESCLUDE MUTAZIONI MT
DNA
20 pz
Mut. in 12 (60%)
67/113
NB
Detection rate circa 60%
POLIMICROGIRIA?
10 pz con MD
CISTI CEREBELLARI?
2 m
Drug resistent EE
Develop Delay
Seconday microc.
MPS of Infancy
↓ I – IV complex
Difetti nella biosintesi di CQ?
80 pz
Dai 4 mesi
-Ipotono
-Ritardo motorio
-Deterioramento in corso di infezioni intercorrenti
-Acrocianosi / Petecchie
-Diarrea emorragica
-Dismorfismi
-Acidosi lattica + ↑ C4 e C5
-Aciduria Etilmalonica
MNGIE: deoxyribonucleosideEE: sulfide
↑S2H
↓SCAD e COX
sulfite
FARS2
..in addition, double immunostaining with the antibodies against FARS2 and COX IV, a mitochondria marker, revealed that FARS2 was colocalized with COX IV..
6 m motor delay
9 m motor regression
15 m myoclonic seizures
Subsequent spastic paraplegia
Aminoacyl-tRNA synthetases (aaRSs) form a set of housekeeping enzymes that play a crucial role in cellular translation. aaRSs chemically ligate tRNAs with their cognate amino acids producing the aminoacyl-tRNAs (aa-tRNAs) that subsequently bind to the elongation factor, facilitating delivery to the ribosome for mRNA decoding
FARS2 (6p25.1)encodes mitochondrial phenylalanyltRNAsynthetase, which catalyzes the attachment of phenylalanine to itscognate mitochondrial tRNA,
Ma
creatina
1) 17 yrs
- 6 m: develop.delay + Feb seizures > DR epilepsy
- 21 m: gen. dystonic movements
2) 11 yrs (1 cusin)
- 13 m dystonic limb movements
Increased GAA - 80 pts Mental retardation + behavioural disturnbance (Autism,ADHD)
Expressive speech delayHypotonia in young children and later ataxia and dystonia (chorea and episodic ataxia aneddoctal)
Seizures (absence, tonic clonic, myoclonic, focal, generalized but expecially head drop seizures, myoclonic, mycolconic astatic, spasms)
EEG aspecific or high amplitude theta/delta, several cases with multifocal spikesBasal ganglia changes in globus pallidum
TP
Nuove malattie / Nuovi geni
7 GENI
AA
22q11.2 del syndrome
PRODH (prol. oxidase)
17 yrs
Previously
Psycomotor delay
OCD
Mild dysmorphic
NO seizures
And than
Schizophrenia
PRODH (22q11) mut
PROLINA da considerare in particolare se dist. psichiatrico è anticipato da RM e epilessia
ucd
ROUTINE in ASD?
AA plasma?
Ac orotico urina?
Ammonio AST ALT?
ASD
1) 12 AA
2) 15 AA
vit
1) 9m rit.psicomot. + corea + a. megal. (madre anemia pernic)
2) 23m diff. alim. + rit. Psicomot + tremore + (alim. esclusiva seno)
3) 9aa debolezza progress. + parestesia AA inf + pancitopenia + sedia a rotelle
4) 15aa anemia perniciosa + dol. addome+ vomito intermittente + astenia + vertigine
5) 18aa debolezza + diff. cammino + parestesie
DG (MMA e cbl)
malnutrizione severa
anemia perniciosa
abuso N2-O
HC transcobalamina 1
TCII transcobalamina 2