1/5. cholesterol supplementation objectively reduces photosensitivity in the smith-lemli-opitz syndrome.Smith-Lemli-Opitz (SLO) affected children have multiple congenital physical and mental abnormalities; photosensitivity to ultraviolet A (UVA) has recently become a recognized feature. We present a patient with SLO and prominent photosensitivity in whom detailed phototesting has been performed at baseline and following 6 months of cholesterol supplementation. There was significant improvement in the symptoms of photosensitivity, confirmed objectively by phototesting and accompanied by partial correction of the biochemical abnormalities seen in SLO. This case report is the first to show that cholesterol supplementation in SLO can lead to an objective improvement in the associated photosensitivity.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
2/5. Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene.The xeroderma pigmentosum group D (XPD) protein is a subunit of transcription factor tfiih with DNA helicase activity. TFIIH has two functions, in basal transcription and nucleotide excision repair. Mutations in XPD that affect dna repair but not transcription result in the skin cancer-prone disorder, xeroderma pigmentosum (XP). If transcription is also affected, the result is the multi-system disorder trichothiodystrophy (TTD), in which there is no skin cancer predisposition, or in rare cases, XP combined with cockayne syndrome. Up till now there have been no reports of combined clinical features of XP and TTD. We have now identified two patients with some features of both these disorders. One of these, XP189MA, a 3-year-old girl with sun sensitivity, mental and physical developmental delay, has XPD mutations not previously reported, and barely detectable levels of nucleotide excision repair. The other, XP38BR, a 28-year-old woman with sun sensitivity, pigmentation changes and skin cancers typical of XP, has a mutation that has been identified previously, but only in TTD patients with no features of XP. The level of repair of UV damage in XP38BR is substantially higher than that in other patients with the same mutation. With both patients, polarized light microscopy revealed a 'tiger-tail' appearance of the hair, and amino acid analysis of the hair shafts show levels of sulfur-containing proteins intermediate between those of normal and TTD individuals. Our findings highlight the complexities of genotype-phenotype relationships in the XPD gene.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
3/5. Photodistributed blue-gray pigmentation of the skin associated with long-term imipramine use.A 72-year-old white woman presented with progressively increasing slate-gray pigmentation of the face and extensor aspect of the forearms, which she had been suffering from for 8 years. She had been taking imipramine for approximately 30 years. Her other medications included ranitidine and anacin. physical examination revealed slate-gray hyperpigmentation of the skin photodistributed on the face (Figs 1, 2) and extensor aspects of the forearms. Relative sparing of the skin folds, mucous membranes, sclerae, teeth, and nails was noted. The remainder of the physical examination revealed no abnormalities. skin biopsy specimens from the right cheek and right forearm were obtained. Histologic examination revealed collections of variably sized, round to ovoid, yellow-brown globular deposits in the upper and mid dermis (Fig. 2). The deposits were identified within macrophages and free within the dermis. The epidermis was unremarkable and free of deposits. The deposits stained for melanin with a Fontana-Masson stain, but did not stain for iron.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
4/5. prenatal diagnosis in a subset of trichothiodystrophy patients defective in dna repair.Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulphur content, and mental and physical retardation. Numerous additional clinical features may be present, producing a very heterogeneous syndrome. Many cases exhibit ichthyosis and photosensitivity. cells from photosensitive TTD patients show reduced dna repair levels similar to those found in xeroderma pigmentosum. TTD patients have a short life expectancy, and no treatment is known or envisaged. We report the prenatal diagnosis of TTD in two French families, based on dna repair measurements in trophoblasts or amniotic cells, with later confirmation by microscopic analysis of the fetal hairs. Although the dna repair defect was less marked in the fetal cells when compared with fibroblasts from the index case, measurement of dna repair by unscheduled DNA synthesis provided unambiguous evidence of defective dna repair in the fetal cells. This method is therefore a suitable prenatal diagnostic test for those TTD families in which a dna repair defect has been identified.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |
5/5. xeroderma pigmentosum (complementation group D) mutation is present in patients affected by trichothiodystrophy with photosensitivity.We studied the response to UV irradiation in cells from four patients, from three apparently unrelated families, affected by trichothiodystrophy (TTD). They showed all the symptoms of this rare autosomal recessive disorder (brittle hair with reduced sulfur content, mental and physical retardation, ichthyosis, peculiar face) together with photosensitivity. We found a decreased rate of duplicative DNA synthesis in stimulated lymphocytes, reduced survival in fibroblasts, and very low levels of unscheduled DNA synthesis (UDS) in Go lymphocytes and fibroblasts after UV irradiation. Complementation studies showed that normal values of UDS are restored in heterokaryons obtained by fusion of TTD cells with normal and xeroderma pigmentosum (XP)-complementation group A-cells. In contrast the defect is not complemented by fusion with XP-complementation group D-fibroblasts.- - - - - - - - - - ranking = 1keywords = physical (Clic here for more details about this article) |