25. Main criteria for Rett
• Partial or complete loss of acquired purposeful hand
skills.
• Partial or complete loss of acquired spoken language
• Gait abnormalities: Impaired (dyspraxic) or absence
of ability.
• Stereotypic hand movements such as hand wringing/
squeezing, clasping/tapping, mouthing and
washing/rubbing automatisms
Ann Neurol 2010
26. Supportive criteria for atypical RTT
• Breathing disturbances when awake
• Bruxism when awake
• Impaired sleep pattern
• Abnormal muscle tone
• Peripheral vasomotor disturbances
• Scoliosis/kyphosis
• Growth retardation
• Small cold hands and feet
• Inappropriate laughing/screaming spells
• Diminished response to pain
• Intense eye communication - ‘‘eye pointing’’
27. Diagnosis of Rett and variants
• Required for typical or classic RTT
– A period of regression followed by recovery or
stabilization
– All main criteria and all exclusion criteria
– Supportive criteria are not required, although often
present in typical RTT
• Required for atypical or variant RTT
– A period of regression followed by recovery or
stabilization
– At least 2 of the 4 main criteria
– 5 out of 11 supportive criteria
Ann Neurol 2010
28. The Role of MeCP2 in Rett Syndrome
• Amir and others (1999)
• 90% of patients with RS have mutations in MECP2
• Two forms of MeCP2: 2A and 2B
• X-linked
MBD: Methy-CpG binding domain
TRD: Transcription repression domain
29.
30. Rett syndrome and its variants
• RTT variants
– Zappella variant (preserved speech variant), characterized by the
recovery of some degree of speech
– the congenital variant (recognized since birth and often caused by
FOXG1 mutation
– the “early onset seizure variant”- or Hanefeld variant.
• MECP2: Methyl-CpG-binding protein 2 (MeCP2)
• CDKL5: Cyclin-dependent kinase-like 5
• FOXG1: forkhead box G1
• NTNG1: Netrin-G1 precursor
36. Cerebrospinal Fluid Concentrations of Folate, Biogenic
Amines and Pterins in Rett Syndrome: Treatment with
Folinic Acid
A. Ormazabal1, R. Artuch1, M. A. Vilaseca1, A. Aracil2, M. Pineda2
1 Department of Clinical Chemistry, Hospital Sant Joan de Déu, Barcelona, Spain
2 Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
Background: Previous studies in Rett syndrome (RS) patients suggested various
abnormalities in biogenic amines, pterins, and folate values in cerebrospinal fluid
(CSF). Our aim was to analyse these metabolites in CSF of 16 RS patients (age
range: 2 - 23 years). Biogenic amines, pterins, and 5-methyltetrahydrofolate were
measured by HPLC with electrochemical and fluorescence detection. Results: CSF
values of 5-methyltetrahydrofolate were decreased in 8 out of 16 RS patients
(average: 53.6 nmol/L; range: 19 - 92) when compared with our reference values
(average: 74.6 nmol/L; range: 45 - 127). These eight patients had epilepsy, while 4
out of 16 RS patients who did not have epilepsy showed normal CSF 5-
methyltetrahydrofolate concentrations. Values of biogenic amines or pterins were
decreased in four of the patients with low values of 5-methyltetrahydrofolate. No
correlation was observed between CSF values of 5-methyltetrahydrofolate and
pterins, biogenic amines, or age. Supplementation with folinic acid was applied in six
out of the eight patients with CSF 5-methyltetrahydrofolate deficiency. An
improvement was noticed in all cases. Conclusions: An important percentage of RS
patients showed 5-methyltetrahydrofolate concentrations under the reference values.
Therefore, analysis of CSF 5-methyltetrahydrofolate seems advisable in RS,
especially in patients with epilepsy and those resistant to antiepileptic drugs.
42. GABA
• The subtle dysfunction of GABAergic neurons
• The GABA level and the ratio of GABA to glutamate
in frontal lobe in autism are significantly lower than
that of the control group
• GABA(A) receptors are reduced in the brain of
individuals with autism.
• GABA transaminase inhibitors such as Vigabatrin may
improve stereotypies in autism and Rett syndrome.
43. • L-carnitine, an important antioxidant that improves
mitochondrial function
• 骨髓移植(2012,小鼠)
44.
45. Absence of MECP2 in RTT causes excessive Sqle transcription
and accumulation of cholesterol.
46. Dextromethorphan and Rett syndrome
• Receptors for glutamate, in particular the NMDA type, are
increased in the brain of young RTT patients (<10 years of
age).
• Dextromethorphan has been shown to block NMDA receptors
and is already used to treat children and infants with
respiratory infections and nonketotic hyperglycinemia.
• Dextromethorphan may improve language and socialization
skills in patients with Rett syndrome.