Based on clinical symptoms, CSF neurotransmitters profile is highly indicative for the diagnosis of aromatic l-amino acid decarboxylase deficiency. Treatment options are limited, in many cases not beneficial, and prognosis is uncertain. Only 15 patients with a relatively mild form clearly improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors.

A crossover study was conducted to examine the effects on plasma lipoprotein concentrations of substituting lean white fish (LWF) for beef, port, veal, eggs, and milk products (BPVEM) within prudent isoenergetic diets. Fourteen premenopausal women received 8784 kJ--20% as protein, 50% as carbohydrates, and 30% as lipids [ratio of polyunsaturated to monounsaturated to saturated fatty acids (P:M:S) of 1:1:1 compared with 0.4:1:1 in preexperimental diet]--and 260 mg cholesterol/d. After 4 wk, the BPVEM diet significantly reduced concentrations of plasma cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol, apolipoprotein B, HDL-apolipoprotein A-I, and LDL-apolipoprotein B (P<0.05) as well as plasma postheparin hepatic triacylglycerol lipase activity compared with the preexperimental diet. These effects are probably attributable to elevation of the P:M:S. These responses were not observed with the LWF diet, suggesting that fish protein in LWF maintains unchanged plasma cholesterol concentrations despite a high P:M:S. The LWF diet, compared with the preexperimental diet, reduced very-low-density-lipoprotein triacylglycerol (P<0.05) and also the ratio of LDL cholesterol to apolipoprotein B (P<0.05), revealing the presence of denser LDL particles. Compared with the BPVEM diet, the LWF diet induced lower concentrations of very-low-density-lipoprotein triacylglycerols (P<0.05) and higher concentrations of LDL triacylglycerol and LDL apolipoprotein B (P<0.05), which were not associated with any increase in lipoprotein lipase activity. These results suggest that LWF as a substitute for BPVEM in isoenergetic diets with an elevated P:S produces minimal improvement in the lipoprotein profile in premenopausal women.

Absent hepatic lipase (HL) activity results in dyslipidemia and premature atherosclerosis. DNA sequencing of the HL gene from subjects with heritable HL deficiency identified a new C to T substitution within exon 8 that in the mature enzyme caused a threonine to methionine change at position 383 (T383M). With a rapid DNA detection method we observed that all 6 individuals with complete HL deficiency from 2 families had the T383M mutation. None of 50 random unrelated unaffected subjects had this mutation. We propose that T383M is specific to families with heritable HL deficiency. Furthermore, structural variation at the HL gene, possibly in combination with other factors, appears to be etiologic in HL deficiency.

A total of 35 homozygous and 1320 heterozygous patients with familial hypercholesterolemia (FH) was screened for the presence of six low‐density lipoprotein receptor (LDLR) gene mutations previously reported among French‐Canadians. The geographic distribution of patients' birthplaces and the relative prevalence of these six mutations in the LDLR gene in the province of Quebec were compared. For this purpose, the 16 administrative regions of the province of Quebec were grouped into seven geographic regions. The relative frequency of the six mutations differed in the seven regions: the > 15 kb deletion (& Delta; >15 kb) had the highest relative frequency in the Bas St‐Laurent/Gaspésie region, and the point mutation in exon 3 had the highest relative frequency in the Saguenay‐Lac‐St‐Jean/Cǒte‐Nord region. In the Montreal area, the Δ >15 kb and the mutation in exon 3 had prevalence rates of 71.2% and 13.0%, respectively, whereas the relative frequencies of the Δ > 15 kb and the point mutation in exon 3 in the Quebec city region were 57.5 and 21.8%, respectively. Finally, in Saguenay‐Lac‐St‐Jean/Cǒte‐Nord, the relative frequency of the Δ > 15 kb only reached 31.5% and the point mutation in exon 3, 59.2%. Thus, on the north shore of the St. Lawrence River, the prevalence of the Δ > 15 kb decreases from west to north‐east, whereas the relative frequency of the mutation in exon 3 appears to increase. These observations provide a better characterization of FH among French‐Canadians of Quebec, a Canadian province with a high prevalence of this inherited disease.

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We have reported three missense mutations (G188E, P207L, and D250N) in the lipoprotein lipase (LPL) gene among French-Canadians, resulting in the absence of measurable postheparin plasma LPL activity in homozygotes. Presence of triglyceride- and cholesterol-rich VLDL, as well as cholesterol-poor HDL particles, has been shown in heterozygotes affected by partial reduction in postheparin LPL activity. However, significant heterogeneity in their plasma triglyceride levels has been found, even among individuals carrying the same LPL gene mutation, indicating that factors other than LPL deficiency could affect the phenotypic expression of hypertriglyceridemia in the heterozygous state. The aim of the present study was to examine the combined effects of abdominal fat accumulation and hyperinsulinemia on plasma triglyceride levels among heterozygous patients for familial LPL deficiency. Based on sex and BMI, 43 heterozygotes (25 women and 18 men) were matched with noncarrier control subjects. Our data indicate that heterozygotes with higher abdominal fat deposition, as defined as waist girth values above the 50th percentile, had higher plasma triglyceride levels than nonobese heterozygotes. However, an important proportion of male heterozygote subjects were hypertriglyceridemic, even in absence of abdominal obesity, suggesting that another factor(s) was involved in the modulation of hypertriglyceridemia in these subjects. Indeed, multivariate analyses revealed that fasting hyperinsulinemia was a significant correlate of hypertriglyceridemia among these heterozygotes. Results of the present study indicate that abdominal obesity and hyperinsulinemia both have deleterious effects on plasma triglyceride levels in familial LPL deficiency. It is suggested that heterozygotes with moderate obesity and/or insulin resistance may be at higher risk of coronary artery disease because of the expression of an atherogenic lipoprotein phenotype among these patients.

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