Treatment of Severe Hypertriglyceridemia During Pregnancy With High Doses of Omega-3 Fatty Acid and Plasmapheresis.

OBJECTIVE: Severe hypertriglyceridemia carries increased health risks, including the development of pancreatitis. The objective of this study was to report on management of 2 cases with severe gestational hypertriglyceridemia. CASES: In case 1, a 33-year-old pregnant woman presented with serum triglyceride level of 14 000 mg/dL after discontinuing hypolipidemic medications. She was treated with Lovaza 12 g/day, and serum triglyceride remained near normal at level of less than 800 mg mg/dL until delivery. In case 2, a 28-year-old patient (29th week gestation) presented with acute pancreatitis and triglycerides >4000 mg/dL. She was treated with Gemfibrozil, Lovaza, insulin infusion, subcutaneous heparin, and escalated to plasmapheresis. She successfully delivered a baby at the week of 36th and her triglyceride level was 304 mg/dL after that. DISCUSSION: Case 1 was treated with high-dose Lovaza and case 2 was treated with plasmapheresis successfully. Triglyceride levels were reduced to less than 500 mg/dL until delivery of healthy babies in both cases. CONCLUSION: Omega-3 fatty acids and plasmapheresis may be effective and safe to treat pregnant women with severe hypertriglyceridemia and pancreatitis.

ADRENAL INSUFFICIENCY SECONDARY TO BILATERAL ADRENAL HEMORRHAGE ASSOCIATED WITH ANTIPHOSPHOLIPID SYNDROME.

OBJECTIVE: Antiphospholipid syndrome (APS) can involve multiple organ systems but endocrine manifestations are rare. In most cases adrenal insufficiency (AI) is the first endocrine manifestation of APS. The prompt diagnosis of AI is critical as this disorder is a life-threatening disease that may lead to fatal outcomes if left untreated. We present a case of AI associated with APS the patient was diagnosed promptly and managed successfully. METHODS: The diagnosis of APS was based on a combination of clinical features (deep venous thrombosis and pulmonary embolism) and laboratory findings (lupus anticoagulant, anticardiolipin antibody, anti-beta-2 glycoprotein-I antibody), without alternative diagnosis to explain the clinical findings. AI was diagnosed by low morning serum cortisol with elevated adrenocorticotropic hormone (ACTH) level as well as an ACTH stimulation test. RESULTS: A 50-year-old male presented with deep venous thrombosis of the left extremity diagnosed by compressive ultrasound, and was subsequently diagnosed with a pulmonary embolism by computed tomography angiography and treated with heparin. Two days later, he developed hypotension and bilateral flank pain, and an abdominal computed tomography scan revealed bilateral adrenal hemorrhage. Laboratory results showed a serum cortisol of 3.3 mcg/dL (stress normal, 25 to 35 mcg/dL) and ACTH of 319 pg/mL (stress normal, 128 to 218 pg/mL), consistent with primary AI. Symptoms improved quickly with hydrocortisone therapy. The patient still required glucocorticoid therapy for at least 4 years thereafter. CONCLUSION: In all cases of adrenal hemorrhage and infarction with unknown etiology, screening with lupus anticoagulant and anticardiolipin antibodies is imperative. Recognition of this high-mortality condition allows for appropriate screening and confirmatory tests leading to a prompt diagnosis and timely management.

A rapidly enlarging painful neck mass in a 59-year-old woman.

Primary care physicians and endocrinologists should be aware that neck masses with concerning features like, in this case, a delay in evaluation and treatment may dramatically shorten a patient's life.

Parkinson's disease and low frequency alleles found together throughout LRRK2.

Mutations within LRRK2, most notably p.G2019S, cause Parkinson's disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. >50% likeness to one set). Set I, affected, carried certain low frequency alleles located in multiple functional domains. Set II was unaffected. Set III, also affected, resembled set II except for slightly elevated frequencies of minor alleles not defining set I. We conclude that certain low frequency alleles distributed throughout LRRK2 are a genetic background to a third of cases, defining a distinct subset.

Genetic control of human brain transcript expression in Alzheimer disease.

We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

Comprehensive analysis of LRRK2 in publicly available Parkinson's disease cases and neurologically normal controls.

Mutation of LRRK2, encoding dardarin, is the most common known genetic cause of Parkinson's disease (PD). The large size of this gene and the relative ease with which the most common mutations can be screened means that although more than 50 LRRK2 screening papers have been published, few have analyzed the entire coding sequence. Furthermore, no comprehensive sequence-based analysis has been performed on control samples. Here, we present sequencing of all coding exons in a series of 275 PD cases and 275 neurologically normal controls and analysis of the LRRK2 locus for whole gene multiplications or deletions. We also present case-control SNP association results using 74 SNPs genotyped across LRRK2. We identified six novel disease-associated missense mutations, including two that altered the same residue of the protein. These data and analysis of previously reported disease-segregating mutations shows that the majority of disease-causing mutations lie in the C-terminal half of the protein.

A survey of genetic human cortical gene expression.

It is widely assumed that genetic differences in gene expression underpin much of the difference among individuals and many of the quantitative traits of interest to geneticists. Despite this, there has been little work on genetic variability in human gene expression and almost none in the human brain, because tools for assessing this genetic variability have not been available. Now, with whole-genome SNP genotyping arrays and whole-transcriptome expression arrays, such experiments have become feasible. We have carried out whole-genome genotyping and expression analysis on a series of 193 neuropathologically normal human brain samples using the Affymetrix GeneChip Human Mapping 500K Array Set and Illumina HumanRefseq-8 Expression BeadChip platforms. Here we present data showing that 58% of the transcriptome is cortically expressed in at least 5% of our samples and that of these cortically expressed transcripts, 21% have expression profiles that correlate with their genotype. These genetic-expression effects should be useful in determining the underlying biology of associations with common diseases of the human brain and in guiding the analysis of the genomic regions involved in the control of normal gene expression.