An 8.5-year-old girl with cerebral X-linked adrenoleukodystrophy is reported from Ben-Gurion University, Beer Sheva, Israel, and Johns Hopkins University, Baltimore, MD. Early development was normal, she could read by 6 years, but severe behavioral problems and deterioration of academic performance developed by 8 years of age. The symptoms of “school phobia” included separation anxiety, oversensitivity to noise, and isolation from peers and teachers. Neurologic exam was normal and intelligence scores by WISC-R were low normal. Achievement was impaired by distractibility and visuospatial defects. Cortisol response to IV ACTH was normal, ruling out adrenal insufficiency. MRI revealed diffuse white matter involvement, most prominent in frontal regions. Very long chain fatty acids in plasma and skin fibroblasts were elevated. Cytogenetic analyses on peripheral lymphocytes showed a deletion at Xq27.2-ter and the unexpected demonstration of a de novo deletion in her paternal X chromosome, involving all of Xq28 and part of Xq27. In combination with the abnormality on the maternal X chromosome, this caused failure of expression of functional ALDP, similar to that in affected males. Neurological and psychological status was stable at 18 months after bone marrow transplant. [1]

COMMENT. Cytogenetic studies are recommended in severely symptomatic X-linked adrenoleukodystrophy heterozygotes. Treatment with bone marrow transplant as recommended in boys with ALD can be beneficial in affected girls.