Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) deficiency: a rare case with bicytopenia and coagulopathy.

Mitochondrial 3-hydroxymethylglutaryl-CoA synthase-2 (HMGCS2) is the main enzyme involved in ketogenesis. It is an essential enzyme for the catalysis of ß-oxidation-derived-acetyl-CoA and acetoacetyl Co-A to produce ß-hydroxy-ß-methylglutaryl-CoA (HMG-CoA) and free coenzyme A.The deficiency of this enzyme (3-hydoxy-3-methylglutaryl-CoA synthase) is a very rare metabolic disorder with limited cases described in the literature. The manifestations of this disease include hypoketotic hypoglycaemia, metabolic acidosis, lethargy, hepatomegaly with fatty liver and encephalopathy.We report a middle childhood male who presented with hepatosplenomegaly, lymphadenopathy and bicytopenia. The case was diagnosed by the whole exome sequencing which revealed a homozygous missense variant of uncertain significance in HMGCS2 gene.

Relation of Wnt Signaling Pathway Inhibitors (Sclerostin and Dickkopf-1) to Left Ventricular Mass Index in Maintenance Hemodialysis Patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in hemodialysis (HD) patients. It predicts poor prognosis. Several inhibitors regulate Wnt canonical pathways like Dickkopf-related protein-1 (Dkk-1) and sclerostin. OBJECTIVES: To investigate the relationship between serum sclerostin, Dkk-1, left ventricular mass (LVM), and LVM index (LVMI) in HD patients. METHODS: This is a cross-sectional study including 65 HD patients in our HD unit. Patients were divided into two groups according to LVMI (group 1 with LVMI < 125 gm/m2 (N = 29) and group 2 with LVMI > 125 gm/m2 (N = 36)). Echocardiographic evaluation of the LVM, aortic, and mitral valves calcification (AVC and MVC) was done. Serum levels of sclerostin and Dkk-1 and patients' clinical and biochemical data were recorded. RESULTS: Group 2 showed significantly higher age, blood pressure, AVC, and MVC and significantly lower hemoglobin, sclerostin, and Dkk-1 levels. LVM and LVMI had a significant linear negative correlation to both serum sclerostin and Dkk-1 (r = -0.329 and -0.257, P=0.01 and 0.046 for LVM; r = -0.427 and -0.324, P=0.001 and 0.012 for LVMI, resp.). Serum Dkk-1 was an independent negative indicator for LVM and LVMI in multiple regression analyses (P=0.003 and 0.041 with 95% CI = -0.963 to -0.204 and -0.478 to -0.010, resp.). CONCLUSION: Serum sclerostin and Dkk-1 were significantly lower in HD patients with increased LVMI > 125 gm/m2, and both had a significant linear negative correlation with LVM and LVMI. Dkk-1 was a significant negative independent indicator for LVM and LVMI in HD patients.

Hepatoprotective activity of Cyperus alternifolius on carbon tetrachloride-induced hepatotoxicity in rats.

OBJECTIVE: The present work explored the potential hepatoprotective activity of total ethanol and successive extracts of Cyperus alternifolius L (Cyperaceae) against carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats and to isolate their bioactive constituents. METHODS: For isolation and identification of the compounds, column chromatography and spectroscopic analysis were used, a model of hepatotoxicity by CCl(4) in rats was used to evaluate the total ethanol extract and its successive fractions. RESULTS: Phytochemical screening of C. alternifolius revealed the presence of different phytochemical groups. The plant proved to be safe for human use because it did not induce any signs of toxicity or mortality in mice when administered orally at doses up to 5000 mg kg(-1). The total alcoholic extract in doses of 100 and 200 mg kg(-1) and the successive extracts (ether, chloroform and ethyl acetate) in a dose of 10 mg kg(-1) exhibited a significant (p ≤ 0.05) protective effect by lowering the elevated serum levels of aspartate aminotransferase: 230.4, 218.8, 224.6, 227.4 and 231.6 U L(-1), respectively, compared with 111.6 U L(-1) for silymarin (25 mg kg(-1)). Serum levels of alanine aminotransferase were also reduced: 77.4, 72.7, 79.7, 76.0 and 79.7 U L(-1) compared to 63.7 U L(-1) for silymarin. Alkaline phosphatase: 164.6, 158.0, 163.6, 154.7 and 166.4 U L(-1) compared to 138.2 U L(-1) for silymarin. Total bilirubin: 0.50, 0.46, 0.55, 0.52 and 0.57 mg dl(-1) compared to 0.42 mg dl(-1) for silymarin. Cholesterol: 213.1, 200.0, 192.7, 193.6 and 197.1 mg dl(-1) compared to 180.3 mg dl(-1) for silymarin. Triglycerides: 237.3, 222.4, 209.5, 206.8 and 210.2 mg dl(-1) compared to 196.8 mg dl(-1) for silymarin. Eight phenolic compounds were isolated from C. alternifolius for the first time and identified as esculetin 1, umbelliferon 2, imperatorin 3, psoralen 4, xanthotoxin 5, quercetin 6, quercetin-3-O-rutinoside 7 and gallic acid 8. CONCLUSIONS: The results concluded that C. alternifolius possesses significant protective effect against hepatotoxicity induced by CCl(4).

Comparative study of the effect of a daily steroid regimen versus a weekly oral pulse steroid regimen on morphological changes, blood sugar, bone mineral density and suprarenal gland activity.

BACKGROUND: The most serious side effects of systemic steroids include osteoporosis and suprarenal suppression. Many steroid regimens have been suggested to minimize these side effects; one of them is oral steroid pulse therapy. OBJECTIVE: To compare the side effects of a daily oral steroid regimen versus a weekly oral steroid pulse regimen on bone mineral density and suprarenal suppression. METHODS: Thirty patients with different skin diseases were divided into two groups: 15 for oral daily steroids (ODS) (group 1) and 15 for weekly oral pulse steroids (WOPS) (group 2). They were evaluated for bone mineral density (measured by DEXA) and suprarenal suppression (measured by serum cortisol level), morphological changes and blood sugar. Treatment was continued for 6 months to 3 years. RESULTS: Cushingoid features in group 1 were observed in 73%, yet they were not detectable in group 2. Disturbed blood sugar in group 1 was 33% and 0% in group 2. The serum cortisol level was lower in patients on ODS than those on WOPS. The effect of WOPS on bone mineral density was very limited in comparison with the ODS. CONCLUSION: Weekly oral steroid pulse therapy induces no significant bone loss and no suprarenal suppression and can be an alternative option in the treatment of chronic disorders requiring long-term oral steroid therapy.