Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome: a treatable genetic liver disease warranting urgent diagnosis.

Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is an autosomal recessive disorder caused by a defect in ornithine translocase. This condition leads to variable clinical presentations, including episodic hyperammonaemia, hepatic derangement, and chronic neurological manifestations. Fewer than 100 affected patients have been reported worldwide. Here we report the first two cases in Hong Kong Chinese, who were compound heterozygous siblings for c.535C>T (p.Arg179*) and c.815C>T (p.Thr272Ile) in the SLC25A15 gene. When the mother refused prenatal diagnosis for the second pregnancy, urgent genetic testing provided the definitive diagnosis within 24 hours to enable specific treatment. Optimal management of these two patients relied on the concerted efforts of a multidisciplinary team and illustrates the importance of an expanded newborn screening service for early detection and treatment of inherited metabolic diseases.

Effects of rosuvastatin on vascular biomarkers and carotid atherosclerosis in lupus: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of rosuvastatin on vascular biomarkers and carotid intima-media thickness (IMT) in systemic lupus erythematosus (SLE). METHODS: SLE patients with inactive disease and subclinical atherosclerosis were randomized in a double-blinded manner to receive either rosuvastatin (10 mg/day) or matching placebo (half in each group were also randomly allocated low-dose aspirin). After 12 months, treatment was unblinded. Patients treated with rosuvastatin and aspirin were continued on the same medications for another 12 months. Plasma levels of homocysteine, high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1, P-selectin, and thrombomodulin were measured at baseline, 6 months, and 12 months. Measurement of carotid IMT was repeated at 24 months. RESULTS: Seventy-two patients were studied (97% women, mean ± SD age 50.8 ± 9.7 years). Thirty-six patients were randomly assigned to each of the study arms (18 patients in each arm also received aspirin). Baseline clinical characteristics and medications were similar between the two groups. At 12 months, the mean low-density lipoprotein cholesterol (mean ± SD 2.62 ± 1.04 mmoles/liter to 1.69 ± 0.72 mmoles/liter; P < 0.001) and median hsCRP levels (1.26 mg/liter, interquartile range [IQR] 2.3 to 0.88 mg/liter, IQR 1.1; P = 0.02) decreased significantly in the rosuvastatin group. There was no significant change in homocysteine, and aspirin use did not influence the levels of the biomarkers studied. A subgroup analysis of patients with a Systemic Lupus Erythematosus Disease Activity Index score ≤2 revealed a significant decrease in hsCRP (1.20 mg/liter, IQR 2.3 to 0.92 mg/liter, IQR 1.1; P = 0.04) and thrombomodulin levels (0.76 ng/ml, IQR 1.2 to 0.67 ng/ml, IQR 1.0; P = 0.001) with rosuvastatin treatment. At 24 months, the IMT of the internal carotid arteries appeared to be decreased in patients treated with rosuvastatin, which was well tolerated. CONCLUSION: In stable SLE patients, low-dose rosuvastatin leads to a significant reduction in hsCRP and thrombomodulin levels, which may possibly help to reduce cardiovascular risk.

Plasma clozapine levels and clinical response in treatment-refractory Chinese schizophrenic patients.

PURPOSE: To evaluate clinical efficacy of clozapine in relation with its plasma level in a group of Chinese patients with treatment-resistant schizophrenia. In addition, the relationship between plasma level and side effects were examined. METHOD: Fifty-one patients with treatment-resistant schizophrenia were put on a fixed dose of clozapine at 300 mg/day for 6 weeks. Non-responders to week 6 received 500 mg/day in subsequent 6 weeks. Responders to week 6 continued to receive 300 mg/day. Clozapine plasma levels were checked at weeks 6 and 12. FINDINGS: No association was found between clozapine plasma level, response and side effects. Sodium valproate was found to elevate clozapine plasma level while lowering norclozapine/clozapine ratio. CONCLUSION: Clozapine plasma level was not found to be associated with response and side effect in Chinese treatment-resistant schizophrenic patients. Various explanations were postulated for the lack of relationship observed between clozapine plasma level and response in this population.