Mona Rashad

Dorfman–Chanarin syndrome in Egypt

Dorfman–Chanarin syndrome (DCS) comprises Ichthyosiform nonbullous erythroderma, vacuoles in leukocytes (Jordans anomaly), and variable involvement of liver, muscle, and central nervous system due to abnormal metabolism of triglycerides. To our knowledge, only 29 cases have been described. We report a patient with DCS. A one-year-old Egyptian boy, the first born to first cousins having generalized ichthyosis and heptosplenomegaly (Figs. 1–3) Generalized ichthyosis and bilateral ectropion were noted at birth. Hepatosplenomegaly was discovered at the age of 9 months and umbilical hernia. He had microcytic hypochromic anaemia and normal results of liver function tests except for raised AST (103 IU/L, normal range: 0–35 IU/L). Lipid analysis showed an increase in triglycerides (351 mg/dl, normal range: 40–160 mg/dl), and very low density lipoproteins (70 mg/dl, normal range: 8–23 mg/ dl), with normal total cholesterol. Abdominal ultrasound study showed an enlarged liver, measuring 14 cm in its long axis at midclavicular line with bright echopattern and no focal lesions. Spleen was slightly bulky with no focal lesions. On biopsy there was moderate expansion of portal tracts by fibrous tissue and some mononuclear inflammatory cells. Hepatocytes showed diffuse marked microand macro-vesicular steatosis. Electron microscopy confirmed the previous findings and demonstrated lipid droplets of homogenous appearance and low electron density. Mitochondria showed mild pleomorphism (Fig. 4). Skin biopsy showed a stratified squamous epithelial covering displaying mild hyperkeratosis and acanthosis. Fat droplets were present in the basal and suprabasal cells. There was also mild infiltration of the upper dermis by mononuclear cells. Electron microscopy confirmed the previous findings and documented fat droplets of variable size, not bounded by membranes, seen in the cytoplasm of basal and suprabasal cells of epidermis and Langerhans cells (Fig. 5,6). Bone marrow was slightly hypocellular with an excess of fat globules. Erythroid precursors were markedly decreased at all stages of maturation. Granulocytopoiesis was active at all stages of maturation. Granulocytic cells, particularly the more mature stages, show marked vacuolation. Serum creatinine phosphokinase level was normal, but electromyogram showed a myopathic pattern.

Growth Hormone/IGF-I Axis and Growth Hormone Receptor Mutations in Idiopathic Short Stature

Background/Aims: It was hypothesized that some children with idiopathic short stature (ISS) may have partial insensitivity to growth hormone (GH). In this study analysis of the GH/IGF-I axis as well as GH receptor (GHR) gene was done in children with ISS to determine the possible underlying factor(s) to their short stature. Methods: Forty-eight patients with a diagnosis of ISS were studied; 33 boys and 15 girls aged 13.6 ± 3.7 years. Molecular analysis of the GHR was performed and GH sensitivity was tested by the IGF-I generation test. Results: Basal IGF-I levels were <–2 SD in 22.9%, and 53.5% showed an IGF-I response below 40% (0–38%) to GH stimulation. GH-binding protein (GHBP) levels were below the normative mean in almost all patients. Mutations in the region of the GHR gene that codes for the extracellular domain of the receptor were found in 15.5%; one newly described mutation was recorded. Conclusion: With the possible exception of the novel G62V mutation, functional studies of the other 2 heterozygous mutations found in 6 of our patients are needed in order to prove their impact on short stature.

TNF-238 polymorphism may predict bronchopulmonary dysplasia among preterm infants in the Egyptian population†

Bronchopulmonary dysplasia (BPD) remains as a major and increasing burden in Egypt.

Transporter TAP1-637G and Immunoproteasome PSMB9-60H Variants Influence the Risk of Developing Vitiligo in the Saudi Population

We evaluated whether TAP1-rs1135216 (p.637D>G) and PSMB9-rs17587 (p.60R>H) were significantly associated with the risk and severity of vitiligo among Saudi patients. One hundred seventy-two subjects were genotyped for the TAP1-rs1135216 and PSMB9-rs17587 variants using endonuclease digestions of amplified genomic DNA. The TAP1-rs1135216 and PSMB9-rs17587 mutant alleles were strongly associated with vitiligo, with odds ratios showing five fold and two fold risks (P < 0.0001 and P = 0.007, resp.). In TAP1-rs1135216, the 637G mutant allele was more frequent in cases (74%) than in healthy controls. In cases, the 60H mutant allele PSMB9-rs17587 was less frequent (42%) than the wild-type 60R allele (58%). Vitiligo vulgaris was the most common type of disease, associated with the DG (55%) and GG (46%) genotypes for rs1135216 and with the RH genotype (59%) for rs17587. The heterozygous 637DG and 60RH genotypes were each linked with active phenotypes in 64% of cases. In conclusion, the TAP1-rs1135216 and PSMB9-rs17587 variants are significantly associated with vitiligo, and even one copy of these mutant alleles can influence the risk among Saudis. Vitiligo vulgaris is associated with genotypes containing the mutant G and H alleles.