SLIDE 3 3/3/2017 3 The work up for ASD/GDD
Any of the aforementioned red flags increases the need for this type of evaluation
Broad based "first pass" includes brain MRI, EEG, microarray, Fragile X and biochemical evaluation Findings on brain imaging Referral to a neurologist for further evaluation If these evaluations are all negative, would consider whole exome and sequencing Refer to a clinical geneticist “Exome Clinic” IF biochemical testing is revealing, may need additional testing, eg mitochondrial genome testing Referral to a metabolic specialist
Imaging Findings that are actionable
X-Linked Adrenoleukodystophy Focal Cortical Dysplasia Left Hemisphere Stroke
Rare but Treatable Causes (examples)
- Phenylketonuria (PKU)
- Tested for in newborn screens throughout the U.S. and most of developed world
- 50+ conditions screened for in the U.S., 12 in Germany and 2 in the U.K.
- Presentation: ASD/ID, Irritability, Seizures, hypopigmentation
- Easily treated with dietary restriction of phenylalanine
- Should ALWAYS consider in child born outside of the US
- Arginase deficiency
- Presents with progressive but slow loss of function
- Analogous to ASD regression
- Also notable for progressive spasticity
- Partially treatable by early diet intervention
- Creatine Deficiency Syndromes
- Pyridoxine Dependent Epilepsy (along with regression and ASD features)
- NMDA receptor encephalopathy
Whole Exome Sequencing
Johnsen J M et al. Blood 2013;122:3268-3275
gDNA
