scholarly journals Clinical Manifest X-Linked Recessive Adrenoleukodystrophy in a Female

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Gyda Hlin Skuladottir Jack ◽  
Karolina Malm-Willadsen ◽  
Anja Frederiksen ◽  
Dorte Glintborg ◽  
Marianne Andersen
Keyword(s):  
Adrenal Glands ◽  
Present Report ◽  
Lower Limbs ◽  
Long Chain Fatty Acids ◽  
Intracellular Accumulation ◽  
Biochemical Tests ◽  
The Central Nervous System ◽  
Climbing Stairs ◽  
Long Chain ◽  
Tendon Reflexes

Adrenoleukodystrophy (ALD) is a rare X-linked inherited leukodystrophy with a reduced capacity for degradation of very long chain fatty acids (VLCFAs). The intracellular accumulation of VLCFA leads to demyelination in the central nervous system (CNS) and cell destruction in the adrenal glands. ALD primarily affects males; however, females may develop milder symptoms that may be difficult to recognize. The present report describes a 35-year-old female who experienced a feeling of heaviness in the upper and lower limbs, pain in both knees, and difficulty climbing stairs, running, and jumping. Clinical examination revealed decreased sensitivity in the feet, particularly to touch. Deep tendon reflexes in the lower limbs were brisk, and Babinski's sign was present bilaterally. Multiple sclerosis (MS) was excluded, and all clinical and biochemical tests were normal. After two years of progressing symptoms, the patient was reevaluated and plasma levels of VLCFA were found to be elevated. Seven years prior to this finding, the patient had been found to be heterozygous for the missense mutation c.1679C>T, p.Pro560Leu on theABCD1gene (ATP-Binding Cassette subfamily D1). In conclusion, the patient's symptoms could be attributed to ALD. The present case underlines the importance of reevaluating family history in women presenting with vague neurological symptoms.

scholarly journals X-linked adrenoleukodystrophy: clinical and laboratory findings in 15 Brazilian patients

2000 ◽  
Vol 23 (2) ◽  
pp. 261-264 ◽  
Author(s):  
Carmen R. Vargas ◽  
Daniella de M. Coelho ◽  
Alethéa G. Barschak ◽  
Carolina F.M. de Souza ◽  
Ana C.S. Puga ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Early Identification ◽  
Signs And Symptoms ◽  
Long Chain Fatty Acids ◽  
Adrenocortical Insufficiency ◽  
Limb Weakness ◽  
Laboratory Findings ◽  
Physician Awareness ◽  
The Central Nervous System ◽  
Long Chain

Adrenoleukodystrophy (X-ALD) is an X-linked recessively inherited peroxisomal disorder, phenotypically heterogeneous, characterized by progressive white-matter demyelination of the central nervous system and adrenocortical insufficiency. We investigated 15 male X-ALD patients varying in age from 7 to 39, diagnosed among 108 suspected patients referred for investigation. Plasma levels of very long chain fatty acids (VLCFA) were measured at our laboratory using gas chromatography (GC). Eleven cases of childhood X-ALD and four cases of adrenomyeloneuropathy (AMN) were diagnosed. Adrenal leukodystrophy insufficiency and limb weakness were the most frequent symptoms, appearing in 12, 8 and 6 of the patients, respectively. Physician awareness of X-ALD seems inadequate to judge by age at diagnosis and lengthy interval between the start of symptoms and diagnosis. This is the first published series of Brazilian patients with X-ALD. We determined signs and symptoms relevant for diagnosis, as early identification seems important for treatment outcome. In addition, diagnosis identifies carriers, who could benefit from genetic counselling and prenatal diagnosis.

scholarly journals Pharmacological complementation remedies an inborn error of lipid metabolism

2019 ◽  
Author(s):  
Meredith D. Hartley ◽  
Mitra D. Shokat ◽  
Margaret J. DeBell ◽  
Tania Banerji ◽  
Lisa L. Kirkemo ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Inborn Error ◽  
Axonal Degeneration ◽  
Parent Drug ◽  
Neurological Deficits ◽  
Long Chain Fatty Acids ◽  
The Central Nervous System ◽  
Cns Penetration ◽  
Long Chain ◽  
Slow Turnover

SummaryX-linked adrenoleukodystrophy (X-ALD) is a rare, genetic disease in which increased very long chain fatty acids (VLCFAs) in the central nervous system (CNS) cause demyelination and axonal degeneration, leading to severe neurological deficits. Sobetirome, a potent thyroid hormone agonist, has been shown to lower VLCFA levels in the periphery and CNS. In this study, two pharmacological strategies for enhancing the effects of thyromimetics were tested in Abcd1 KO mice, a murine model that has the same inborn error in metabolism as X-ALD patients. First, a sobetirome prodrug (Sob-AM2) with increased CNS penetration lowered CNS VLCFAs more potently than sobetirome, and was better tolerated with lower peripheral exposure, but was unable to unable to break the efficacy threshold of CNS VLCFA lowering in Abcd1 KO mice. Second, co-administration of thyroid hormone with sobetirome enhanced VLCFA lowering in the periphery compared to sobetirome alone but did not produce greater lowering in the CNS. These data suggest that the extent of CNS VLCFA lowering in Abcd1 KO mice is limited by a mechanistic threshold related to slow turnover kinetics, potentially related to the lack of frank X-ALD disease in this model. However, Sob-AM2 has improved potency at correcting the lipid abnormality associated with X-ALD in the CNS with better tolerance than the parent drug sobetirome.

The biochemistry of copper deficiency - II. Synthetic processes

1956 ◽  
Vol 145 (919) ◽  
pp. 195-205 ◽  
Keyword(s):  
Fatty Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Nucleic Acid ◽  
Copper Deficiency ◽  
Long Chain Fatty Acids ◽  
Phospholipid Synthesis ◽  
The Central Nervous System ◽  
Long Chain ◽  
Chain Fatty Acids

The biochemistry of copper deficiency is studied in order to gain some understanding of the metabolic disturbances which lead to demyelination of the central nervous system in disease. In the preceding paper we reported our investigation of the enzyme systems, blood chemistry and amino-acid excretion in copper-deficient rats, and in this paper extend the study to investigate the syntheses of phospholipid, long-chain fatty acids, ribose nucleic acid, protein and protohaem. Phospholipid synthesis is found to be depressed considerably in copper deficiency. This is due to a failure in the process of condensation of acyl CoA with α-glycerophosphate to form phosphatidic acids. The reasons are discussed. The syntheses of long-chain fatty acids and ribose nucleic acid are normal, whilst the synthesis of protein is inconstantly affected by copper deficiency. Protohaem synthesis is depressed by a degree which exactly parallels the anaemia. The conclusion is drawn that the anaemia is due to a decrease in haematopoiesis rather than an increased destruction of red cells. The possible interrelationships of the disturbances of phospholipid synthesis and cytochrome oxidase activity and the relevance of each to demyelination of the central nervous system are discussed.

Postprandial Activation of Coagulant Factor VII by Long-chain Dietary Fatty Acids

1996 ◽  
Vol 76 (03) ◽  
pp. 369-371 ◽  
Author(s):  
T A B Sanders ◽  
G J Miller ◽  
Tamara de Grassi ◽  
Najat Yahia
Keyword(s):  
Fatty Acids ◽  
Dietary Fatty Acids ◽  
Factor Vii ◽  
Fat Intake ◽  
Long Chain Fatty Acids ◽  
Postprandial Lipaemia ◽  
Increased Risk ◽  
Coagulant Activity ◽  
Long Chain Triglycerides ◽  
Long Chain

SummaryFactor VII coagulant activity (FVIIc) is associated with an increased risk of fatal ischaemic heart disease (IHD). Several reports have suggested that dietary fat intake or hypertriglyceridaemia are associated with elevated levels of FVII. This study demonstrates that an intake of long-chain fatty acids sufficient to induce postprandial lipaemia in healthy subjects leads to a substantial elevation in both FVIIc and the concentration of FVII circulating in the activated form. Such an increase in FVIIc could not be induced by medium-chain triglycerides. These results suggest that the consumption of a sufficient amount of long-chain triglycerides to induce postprandial lipaemia induces the activation of FVII.

scholarly journals Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 682-682 ◽  
Author(s):  
Kayla Dillard ◽  
Morgan Coffin ◽  
Gabriella Hernandez ◽  
Victoria Smith ◽  
Catherine Johnson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Weight ◽  
Fatty Acid ◽  
Liver Injury ◽  
Olive Oil ◽  
Coconut Oil ◽  
Long Chain Fatty Acids ◽  
Medium Chain ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

Long chain fatty acids can form aggregates and affect the membrane integrity

2021 ◽  
Vol 204 ◽  
pp. 111795
Author(s):  
Gulen Melike Demirbolat ◽  
Goknil Pelin Coskun ◽  
Omer Erdogan ◽  
Ozge Cevik
Keyword(s):  
Fatty Acids ◽  
Membrane Integrity ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids
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