GALACTOSEMIA STUDIES

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GALACTOSEMIA STUDIES

• Past, Pilot, and Proposed

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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
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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

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SPEECH

• Reduced tongue strength 73
• Decreased phonation duration 64
• Reduced articulation 12
• Dysarthria
  24
• Apraxia of speech 9

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FERTILITY REPRODUCTION

•  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

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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

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WHAT WE DIDNT 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

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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.
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METHODS

• 10 Adults with galactosemia (5 males/5 females)
• Neuroimaging Study MRI
• Structural
• DTI
• Functional MRI (fMRI)
• EEG
• Neuropsychological Evaluation
• Neurological Assessment

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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
  little or no chronic complications.

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• STAY TUNED!