A mild form of Alstrom disease associated with metabolic syndrome and very high fasting serum free fatty acids: two cases diagnosed in adult age.

Alstrom syndrome (ALMS) is a very rare genetic autosomal recessive disease, characterized by early-onset severe abdominal obesity, impaired glucose tolerance or type 2 diabetes with insulin resistance, acanthosis nigricans, hyperlipidemia, childhood progressive retinal degeneration or retinitis pigmentosa and neurosensory hearing loss or deafness, cardiomyopathy, and other endocrine disorders. Genetic studies locate the ALMS gene on chromosome 2p12-13. The aim of this paper is to describe and discuss two unrelated cases of a mild ALMS form diagnosed after the age of 40 and 60, respectively, in adult fertile female patients. These cases showed several features of the disease plus other alterations characteristic of the classic "metabolic syndrome," including hypertension, hyperfibrinogenemia, and thrombotic states. Moreover, the patients had very high fasting serum free fatty acid (FFA) levels (2150 and 1919 micromol/L, respectively), which proved to be sensitive to inhibition by oral glucose tolerance test (OGTT)-induced hyperinsulinemia as well as to caloric restriction. ALMS may have an adverse prognosis and is often underdiagnosed. Its mild form, which allows a long survival, may also be associated with the late complications of the metabolic syndrome, leading to increased vascular risk.

Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.

The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P < .01 and -52%, P < .0001, respectively). Both lean and obese patients affected by chronic active B or C hepatitis (n = 26), with autoantibodies and without signs of hepatic insufficiency or cirrhosis, presented reduced TG (-57%, P < .01 and -61%, P < .001, respectively). A marked TG decrease (-73%, P < .001) was observed in the lean patients affected by lupus-like syndrome (n = 7). The lean and obese patients with systemic lupus erythematosus or rheumatoid arthritis (n = 11) showed TG decrease (-66%, P < .01 and -55%, P < .05, respectively). In patients affected by anamnestic allergy or atopic dermatitis/asthma (n = 66), both lean and obese, TGs were reduced (-67%, P < .0001 and -62%, P < .001, respectively). In isolated cases of diverse autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barré syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P < .01 and -57%, P < .01, respectively). Concerning FFA (n = 69), value in lean patients (n = 22) vs that in lean controls (n = 18) was increased (520 +/- 31 vs 299 +/- 30 mcEq/L, +74%, P < .001), whereas value in obese patients (n = 18) vs that in obese control subjects (n = 11) was decreased (542 +/- 34 vs 774 +/- 62, -30%, P < .01). This opposite behavior of FFA in lean and obese patients needs to be confirmed. Data in this study seem to indicate that low TG value may be a precocious marker of autoimmunity or immune system hyperreactivity.

A clinical variant of familial Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive inherited disease consisting of (1) partial oculocutaneous albinism (with nystagmus, strabism, and visual acuity loss), (2) platelet storage pool deficiency (with bleeding diathesis), and (3) disorder of "ceroid" metabolism with a multisystem tissue lysosomal ceroid deposition. HPS is less uncommon in Puerto Rico, where the most important studies have been performed, but is a very rare disease in Europe. HPS basic defect remains unknown, even if an HPS-causing gene was identified in chromosome segment 10q23-q23.3, and several mutations have been reported. The aim of this article is to discuss, on the basis of a review of relevant literature, a new familial HPS clinical variant observed in 2 young sisters (aged 16 and 23 years old, respectively), characterized by the typical symptoms of this syndrome. Our patients also suffered from diffuse interstitial pulmonary disease and an unexpectedly increased platelet aggregation and were prone to bacterial infections. Interestingly, we observed urinary tract abnormality in the younger HPS sister and a porencephalic cyst in the older HPS sister; both of these developmental defects have been reported in the Cross syndrome (or oculocerebral hypopigmentation syndrome). It seems that in our patients, an overlapping of the phenotypic manifestations of different rare syndromes may be present. The presence of ceroid-like autofluorescent material in urinary sediment together with the histologic aspects and the autofluorescence of oral mucosa biopsy are consistent with a ceroid-like lipofuscin storage. HPS should be carefully tested for in suspected cases to prevent the severe visual impairment, rapidly progressive pulmonary fibrosis, and other complications associated with this disorder.

Low fasting serum triglyceride and high free fatty acid levels in pulmonary fibrosis: a previously unreported finding.

OBJECTIVE: The authors describe here the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in pulmonary fibrosis, a finding that has never been reported before. PATIENTS AND METHODS: TGs were measured in: (a) 44 patients (3 male and 41 female; mean age SEM: 63.06 +/- 4.04 years) who have been hospitalized in the authors' department in the past 2 years for chronic interstitial or fibrosing pulmonary disease (FP); (b) 20 patients (4 male and 16 female; mean age: 69.80 +/- 2.96 years) affected by various nonfibrosing pneumopathies or bronchopathies (NFP); (c) 110 control subjects (CS), composed of 15 male and 95 female consecutive patients (mean age: 67.52 +/- 1.52 years) hospitalized in 1999 for minor nonlung-related illnesses. In 24 FP and 36 CS patients, FFA have also been measured. All subjects investigated had no clinical or laboratory evidences of liver, kidney, or thyroid diseases, nor a history of hormonal treatment, alcohol consumption, smoking, or dietary disorders. None of the subjects investigated was under treatment with lipid lowering agents or with other drugs that could affect the levels of TG or FFA or their measurement (including ascorbic acid). RESULTS: Compared with CS, the FP group showed a 61% reduction of TG (0.64 +/- 0.03 vs 1.63 +/- 0.08 mmol/L; P <.001), whereas no significant difference was observed between NFP and CS groups. Serum FFA in FP showed a 63% increase compared with CS (P <.01). In the FP group, TGs were also low in 5 patients with type 2 diabetes (0.76 +/- 0.11 mmol/L, -53%, P <.001) and in 6 obese (body mass index [BMI] > 29 kg/m2) subjects (0.51 +/- 0.03, -69%, P <.01), although it is known that TGs are often elevated in diabetes and obesity. CONCLUSIONS: Chronic interstitial or pulmonary fibrosis is associated with low TG and high FFA levels. Although it is known that the lung contains lipoprotein lipase and is a significant source of plasma postheparin lipase activity, the mechanisms of this change remain to be clarified. Since insulin-like growth factor-I (IGF-I) is known to lower TG and increase FFA, a role could be played by the enhanced production of IGF-I that has been reported to occur in pulmonary fibrosis.