The impact of a ketogenic diet and liver dysfunction on serum very long-chain fatty acids levels.

Peroxisomes play an essential role in mammalian cellular metabolism, particularly in oxidation fatty acid pathways. Serum very long-chain fatty acids (VLCFA), the main biochemical diagnostic parameters for peroxisomal disorders, were examined in 25 neurological patients with epilepsy on a ketogenic diet and 27 patients with liver dysfunction. The data show that patients on a ketogenic diet have increased levels of C22:0 and C24:0, but not C26:0, and normal C24:0/C22:0 and C26:0/C22:0. Patients with liver insufficiency showed a slightly elevated level of C26:0, a normal level of C24:0 and a decreased level of C22:0; thus in 21/27 the ratio of C24:0/C22:0 was increased and 15/27 the ratio of C26:0/C22:0 was increased.

Reproductive function in men affected by X-linked adrenoleukodystrophy/adrenomyeloneuropathy.

BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is the most frequent, severely neurodegenerative, clinically heterogeneous peroxisomal disorder, the signs of which are a consequence of myelin, adrenal cortex, and testes impairment. OBJECTIVE: We studied testosterone, LH, and FSH levels in X-ALD/adrenomyeloneuropathy (AMN) patients. We evaluate the ability to procreate of these patients by analysis of pedigree and family screening by detection of very long-chain fatty acid (VLCFA) levels. SUBJECT AND METHODS: Seventeen patients with X-ALD/AMN (16 with AMN and one asymptomatic) aged 24-48 (mean±S.D., 34.7±5.9) years, were identified based on the clinical picture, magnetic resonance imaging, and the presence of increased serum VLCFA levels. Nine X-ALD/AMN patients' daughters, mean ages ±S.D.=7.7±3.8 years, were identified as heterozygote by elevated VLCFA levels. Serum VLCFA levels were determined as ester derivatives by a gas chromatography method. Serum testosterone, LH, and FSH levels in X-ALD/AMN patients were detected by IRMAs. RESULTS: Serum testosterone levels were at the lowest levels of normal range but serum LH and FSH concentrations were increased in 57.1 and in 42.9% of X-ALD/AMN patients respectively. Among the 11 investigated of X-ALD/AMN married adult men, nine had produced offspring, a total of 13 children. All patients' daughters showed elevated serum VLCFA at heterozygote levels. CONCLUSION: In this study, we report that in a group of X-ALD/AMN married adult men, we did not find a significant decrease in fertility compared with the Polish population (18.2 vs 15%).

Decreasing serum VLCFA levels in ageing X-ALD female carriers.

Adrenoleukodystrophy is an X-linked severe demyelinating disease with pathognomonic accumulation of saturated very long-chain fatty acids (VLCFA) in tissues and body fluids in affected males. The identification of women heterozygotes is also based on increased serum VLCFA concentrations. We describe the results of measuring serum VLCFA concentrations in 59 females of various ages with heightened risk of carrier status. In female carriers aged 22-50 years we found serum VLCFA concentrations in a range characteristic of heterozygotes; VLCFA levels were normal in female carriers aged 55-64 years. In women aged 37-50 years in whom repeat studies of VLCFA concentration were performed after 5 years, a reduction in VLCFA was observed. The results we obtained point to a reduction of serum VLCFA concentrations as X-ALD heterozygotes age.

MRI findings in an asymptomatic boy with X-linked adrenoleukodystrophy and his symptomatic mother.

We report an asymptomatic 15-year-old boy with X-linked adrenoleukodystrophy and his symptomatic 38-year-old mother. MRI revealed similar, subtle high-signal lesions in the periventricular white matter of the parieto-occipital regions, without involvement of the corpus callosum, more pronounced in the mother.

[Cerebral adrenomyeloneuropathy as a late type of adrenoleukodystrophy: case report]. / Mózgowa odmiana adrenomyeloneuropatii jako pózna postac adrenoleukodystrofii. Opis przypadku.

Adrenoleukodystrophy (ALD) is a hereditary disease related to abnormalities in the structure and function of peroxisomes. The nature of disorder arises from defective process of beta-oxidation of very-long-chain fatty acids and their accumulation in various organs. ALD may present as a few phenotypes urologic symptomatology of which depends on proportions of the brain, spinal cord and peripheral nerves affection. Below, we present a case (and its family) of a cerebral type of adrenomyeloneuropathy--a rare form of adrenoleukodystrophy, and discuss its clinical manifestation as well as biochemical, hormonal, electrophysiological, neuropsychological and magnetic resonance imaging (MRI) diagnostics.

Very long-chain fatty acids in Rett syndrome.

UNLABELLED: Rett syndrome (RS), found exclusively in girls, is characterised by a global deceleration of psychomotor development, loss of acquired speech, loss of manual skills and subsequent deceleration of head growth. The cause of this syndrome is so far unknown. To date there are no biological markers for RS; clinical diagnostic criteria were proposed by the Rett Syndrome Diagnostic Criteria Work Group 1988. The first objective of this study was to assay the levels of very long-chain fatty acids (VLCFA), i.e. C22:0, C24:0, C26:0, by gas chromatography in sera of 30 girls with RS. The VLCFA levels in the studied group were lower than the reference range for healthy children and control group. VLCFA levels were again measured after 2 months of L-carnitine administration in the same groups. VLCFA levels had increased. It is possible that the low VLCFA levels have some relation to the lowered carnitine levels. It may be that low carnitine levels impede transportation to mitochondria, thus the oxidation of long-chain fatty acids is inhibited, and compensated to a certain extent by intensified beta-oxidation of VLCFA in the peroxisomal system. Raising carnitine levels could improve substrate delivery for mitochondrial beta-oxidation of long-chain fatty acids, thus reducing the use of VLCFA as substrates for beta-oxidation. We consider VLCFA to be secondary to the pathogenesis of RS, but the possible abnormalities in their levels may provide an insight into the development of this disease. CONCLUSION: Very long-chain fatty acid and carnitine levels are decreased in Rett syndrome L-Carnitine administration increased very long-chain fatty acid levels in serum.

[Examination of very long chain fatty acids in diagnosis of x-linked adrenoleukodystrophy]. / Badanie stezen bardzo dlugolancuchowych kwasów tluszczowych w diagnostyce adrenoleukodystrofii sprzezonej z chromosomem X.

X-linked adrenoleukodystrophy (X-ALD) (McKusick 300100) is a relatively common disorder due to activity deficiency of a peroxisomal transporter of very long chain acyl-CoA synthetase it causes accumulation of endogenous and exogenous saturated very long chain fatty acids (VLCFA) in plasma and in all tissues. X-ALD is characterised by phenotypic variability, about 80% of patients present more or less progressive demyelinization and adrenal insufficiency. The remaining patients have isolated adrenocortical insufficiency or are asymptomatic or presymptomatic. The measurement of VLCFA accumulation in plasma using the GC-MS method is the basis of diagnosis of X-ALD. Among 162 plasma samples from patients suspected of X-ALD, only 2 were from patients suspected of adrenomyeloneuropathy (AMN). In the analysed material we identified 13 X-ALD hemizygotes and 7 X-ALD heterozygotes. Twelve patients presented the childhood cerebral form of X-ALD. VLCFA profiles in plasma were analysed in 6 patients who were on a diet and Lorenzo oil.