Past, Pilot, and Proposed. Over one weekend in Boston, we conducted medical, nutritional, genetic,...
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Transcript of Past, Pilot, and Proposed. Over one weekend in Boston, we conducted medical, nutritional, genetic,...
Over one weekend in Boston, we conducted
medical, nutritional, genetic, neurological, speech/language, laboratory, and psychological examinations in 33 adults with classic galactosemia.
I. PAST
Supported by Parents of Galactosemic Children, Inc (Galactosemia Foundation) And New England Genetics Collaborative
Full Scale IQ 88 (range: 55-122) Tremor 46% Employed 79% Married or living with partner 27% Anxiety (Currently or in the past) 52% Depression (Currently or in the past) 39% Low bone density 24%
RESULTS
Reduced tongue strength 73% Decreased phonation duration 64% Reduced articulation 12% Dysarthria 24% Apraxia of speech 9%
SPEECH
WOMEN
Primary ovarian insufficiency 100% Average age of menarche 15 years Pregnancy 1 Births 1
MEN Average age of puberty 13 years Fathered children 2
FERTILITY & REPRODUCTION
Low calcium intake 80% Low vitamin D intake 75% Normal height for males & females Normal body mass index (BMI) 58% Underweight 13% (females only) Overweight 25% females/24% males Obese 13% females/6% males
NUTRITION
Adult Phenotype
height is well within average range Speech issues resolve 46% had tremor Few men engage in sexual relationships and father
children Underlying deficit may be motor
No genotype/phenotype correlation Older subjects no worse than younger
subjects
WHAT WE DIDN’T KNOW BEFORE
Specific aims
Assess the relevance of neuroimaging and electroencephalogram (EEG) measurements in adults with galactosemia in explaining the pathogenesis and timing of neurocognitive impairments and neurological symptoms in galactosemia.
To determine if there is evidence for a right hemispheric developmental deficit in galactosemia.
II. PILOT STUDY
Supported by The Galactosemia Foundation and, in part, by New EnglandGenetics Collaborative.
10 Adults with galactosemia (5 males/5
females) Neuroimaging Study – MRI
Structural DTI Functional MRI (fMRI)
EEG Neuropsychological Evaluation Neurological Assessment
METHODS
Specific aim #1 Recruit 2,200 subjects with
hereditary galactosemia from North America and Europe over a five year period of time.
Specific aim #2 Perform comprehensive phenotyping on 150 adult subjects with galactosemia.
Specific aim #3 Establish a data coordinating center for an International Galactosemia Research Consortium and Galactosemia Bio-repository at the Manton Center for Orphan Disease Research at Children's Hospital Boston
Specific aim #4 Perform whole genomic DNA sequencing on 10 subjects with Q188R/Q188R genotype and severe neurological complications and on 10 subjects with Q188R/Q188R genotype and little or no chronic complications.
III. PROPOSED STUDY