Characteristics: A neurodegenerative brain disorder resulting in macrocephaly and lack of head control by three to five months of age. Affected individuals fail to achieve sitting, ambulation, or speech, and often die in early childhood to teen years.
Incidence: 1 in 10,000 Ashkenazi Jewish individuals, unknown in other ethnicities.
Inheritance: Autosomal recessive.
Cause: Deleterious ASPA gene mutations.
Mutations Tested: Y231X(C>A), E285A, A305E, 433(-2)A>G; benign polymorphism Y231Y(C>T).
Clinical Sensitivity: 98 percent in Ashkenazi Jewish; 55 percent in non-Ashkenazi Jewish.
Methodology: Genomic DNA is assayed by PCR and allele-specific primer extension by bead array with fluorescence detection.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: Deleterious mutations other than Y231X, E285A, A305E, 433(-2)A>G will not be detected. Rare diagnostic errors may occur due to primer site mutations.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.
Refer to Statement C under Testing Information at http://www.aruplab.com.