Past, Pilot, and Proposed. Over one weekend in Boston, we conducted medical, nutritional, genetic, neurological, speech/language, laboratory, and.

Past, Pilot, and ProposedPast, Pilot, and Proposed

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

STAY TUNED!