Wolfram syndrome (DIDMOAD) is a rare diffuse neurodegenerative disorder characterised by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and a wide variety of abnormalities of the central nervous system, urinary tract and endocrine glands. It may be familial or sporadic. Reported features on MRI of the brain are absence of the physiological high signal of the posterior lobe of the pituitary, shrinkage of optic nerves, chiasm and tracts, atrophy of the hypothalamic region, brain stem, cerebellum, and cerebral cortex. We report a 12-year-old girl with a 5-year history without brain stem, cerebellar or cerebral atrophy. MRI showed an unusual feature: a focus of high signal on PD- and T2-weighted images in the right substantia nigra. This is consistent with previously reported neuropathological post-mortem studies, but has never been reported in vivo.

A significantly smaller volume of the affected globe is an additional feature of Coats disease.

Pseudoxanthoma elasticum (PXE) is a mendelian disorder characterized by calcification of elastic fibers in skin, arteries, and retina. It results in dermal lesions, arterial insufficiency and retinal hemorrhages, leading to macular degeneration. PXE is transmitted either as an autosomal dominant or recessive trait and several sporadic cases have been observed. Mutations in the ABCC6 gene have been identified very recently in patients. Here, we report on a large Italian family affected by pseudoxanthoma elasticum for which linkage analysis had pointed to a region encompassing markers D16S3069-D16S405-D16S3103; hemizygosity of marker D16S405 allowed us to detect a submicroscopic deletion of at least 900 kb involving ABCC6, ABCC1, and MYH11. Mutation analysis on the other allele of the family, as well as on two additional sporadic cases, revealed nonsense (Y227X, R518X, R1164X) and frame-shift (c.960delC) mutations in ABCC6 (MRP6) further confirming the role of this multi-drug resistance gene in the etiology of pseudoxanthoma elasticum. Furthermore, clinical re-examination of members of the family harboring the deletion led to the detection of additional features, potentially caused by the deletion of the MYH11 gene. In the course of the analysis five nonpathogenic variants were found in ABCC6: 1233T>C, 1245G>A, 1838 T>G (V614A), 1890C>G, and 3506+83C>A. Hum Mutat 18:85, 2001.

Conclusions Type II tyrosinaemia in Italy has no regional preponderance. Neuromotor retardation and/or microcephaly seem to be correlated with the higher values of tyrosine. Enzyme studies have been refused in all patients. Treatment with a low tyrosine diet has been successful when accepted: since in many patients the diagnosis was made rather late, it is not possible to evaluate the results of the diet for the prevention of neuromotor retardation.

No abstract