Past, Pilot, and Proposed
I. PAST

 Over one weekend in Boston, we conducted medical,
nutritional, genetic, neurological, speech/language,
laboratory, and psychological examinations in 33
adults with classic galactosemia.
Supported by Parents of Galactosemic Children, Inc (Galactosemia Foundation)
And New England Genetics Collaborative
RESULTS

 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%
SPEECH

 Reduced tongue strength
 Decreased phonation duration
 Reduced articulation
 Dysarthria
 Apraxia of speech
73%
64%
12%
24%
9%
FERTILITY &
REPRODUCTION

 WOMEN




Primary ovarian insufficiency 100%
Average age of menarche
15 years
Pregnancy
1
Births
1
MEN
 Average age of puberty
 Fathered children
13 years
2
NUTRITION

 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
WHAT WE DIDN’T KNOW
BEFORE

 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
II. PILOT STUDY

 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.
Supported by The Galactosemia Foundation and, in part, by New England
Genetics Collaborative.
METHODS

 10 Adults with galactosemia (5 males/5 females)
 Neuroimaging Study – MRI
 Structural
 DTI
 Functional MRI (fMRI)
 EEG
 Neuropsychological Evaluation
 Neurological Assessment
III. PROPOSED STUDY

 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

 STAY TUNED!