Diverse clinical manifestations of X-linked adrenoleukodystrophy in a Chinese family with identical multisite variants of ABCD1 gene.

OBJECTIVE: This study summarized the clinical characteristics of X-linked adrenoleukodystrophy (X-ALD) patients in this family, and two different manifestations of the same variants in a Chinese family were reported in this article. That conducted a follow-up study to further clarify the characteristics of this disease. BASIC METHODS: Clinical data and test results were analyzed, and the exon region of ALD-related gene ABCD1 was sequenced by Sanger sequencing. MAIN RESULTS: Gene analysis showed that there were three ABCD1 variants in the proband, c.1047C>A, c.1415-1416delAG and c.1548G>A. The elder brother of the proband had the same three variants as the proband, but showed different clinical symptoms. The mother was the carrier of three variants. Multisite variants were uncovered in this family, which caused two different manifestations of adult-onset childhood cerebral ALD and adrenomyeloneuropathy. PRINCIPAL CONCLUSION: These findings further increase our knowledge about ABCD1 mutations and the associated phenotypes, which is beneficial for the genetic counseling of patients with X-ALD.

[Toxic effects of ammonium perchlorate on thyroid of rats].

OBJECTIVE: To study the effects of toxicity of ammonium perchlorate (AP) on thyroid of rats. METHODS: Eighty-eight Wistar rats were treated orally with different dosages of AP. Three treated groups received 129, 257, 514 mg.kg(-1).d(-1) of AP respectively and one control group drunk water for 13 weeks. Another 3 groups received 1.2, 46.5, 465.0 mg.kg(-1).d(-1) of AP respectively and one control group drunk water for 36 weeks. The behavior and change of body weight in rats were observed. The levels of thyroid hormones in serum were measured and the pathological changes of thyroid tissue were observed as well. RESULTS: There were no differences in behavior and change of body weight between different AP exposure time. When the rats were treated with AP 514 mg for 13 weeks, free triiodothyronine (FT3, 2.48 pmol/L), free thyroxin (FT4, 13.33 pmol/L) were lower than those in control group (3.24, 20.92 pmol/L respectively, P<0.05). Thyroid-stimulating hormone (TSH, 0.375 mIU/L), thyroglobulin (TG, 3.37 microg/L) were higher than those in control group (0.29 mIU/L, 2.00 microg/L respectively, P<0.05). When the rats were treated with AP 465 mg for 36 weeks, FT3 (2.65 pmol/L) was lower than that in control group (4.97 pmol/L, P<0.01). FT4 in 46.5, 465 mg groups (10.63, 2.17 pmol/L respectively) were lower than that in control group (15.74 pmol/L, P<0.05, P<0.01). TSH in 465 mg group (0.34 mIU/L) was higher than that in control group (0.14 mIU/L, P<0.05). Histopathologic examination showed that follicle proliferation, no colloid in follicle, gore, follicular diminishing or atresia were found in 46.5, 465 mg groups with a dose-effect relationship. CONCLUSIONS: The toxic effects of AP on the growth of rats were not found, but those on the thyroid of rats were found significantly. Thyroid is the target organ of AP. It is considered that none effect dose of AP for rat thyroid may be 1.2 mg.kg(-1).d(-1), its threshold dose may be 46.5 mg.kg(-1).d(-1).