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1.
J Clin Lab Anal ; 35(3): e23672, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33258201

ABSTRACT

BACKGROUND: Our aims were to describe the first Mexican patient with abetalipoproteinemia and to perform a comparative analysis of biochemical, clinical, and genetic characteristics of 100 cases reported in the literature. METHODS: We performed biochemical and molecular screenings in a Mexican girl with extremely low lipid levels and in her family. Further, we integrated and evaluated the characteristics of the cases with abetalipoproteinemia described in the literature. RESULTS: Our patient is a six-year-old girl who presented vomiting, chronic diarrhea, failure to thrive, malabsorption, acanthocytosis, anemia, transaminases elevation, and extremely low lipid levels. MTTP gene sequencing revealed homozygosity for a novel mutation p.Gly417Valfs*12 (G deletion c.1250). With the analysis of the reported cases, 60 clinical features (14 classical and 46 non-classical) were observed, being the most common acanthocytosis (57.5%), malabsorption (43.7%), and diarrhea (42.5%); 48.8% of the patients presented only classic clinical features, while the remaining 51.2% developed secondary effects due to a fat-soluble vitamin deficiency. An odds ratio analysis disclosed that patients diagnosed after 10 years of age have an increased risk for presenting clinical complications (OR = 18.0; 95% CI 6.0-54.1, p < 0.0001). A great diversity of mutations in MTTP has been observed (n = 76, being the most common p.G865X and p.N139_E140) and some of them with possible residual activity. CONCLUSION: The first Mexican patient with abetalipoproteinemia presents a novel MTTP mutation p.Gly417Valfs*12. Three factors that could modulate the phenotype in abetalipoproteinemia were identified: age at diagnosis, treatment, and the causal mutation.


Subject(s)
Abetalipoproteinemia/genetics , Carrier Proteins/genetics , Mutation , Abetalipoproteinemia/etiology , Adolescent , Adult , Child , Female , Humans , Male , Mexico , Middle Aged , Pedigree
2.
Ideggyogy Sz ; 68(11-12): 417-21, 2015 Nov 30.
Article in English | MEDLINE | ID: mdl-26821516

ABSTRACT

Hyperglycaemia induced movement disorders, such as hemiballism are rare disorders. The syndrome is characterised by the triad of hemiballism, contralateral T1-hyperintense striatal lesion and non-ketotic hyperglycaemia. Here we report a patient with untreated diabetes presenting with acute onset of hemiballism. MRI revealed T1 hyperintensity of the head of the caudate nucleus and the anterior putamen. The patient also had acantocytosis. Based on the detailed examination of the neuroradiological results and earlier findings we will discuss the pathomechanism. Based on previous findings microhemorrhages, extensive mineralisation, gemistocytic astrocytosis might play a role in the development of the imaging signs. The connectivity pattern of the striatal lesion showed extensive connections to the frontal cortex. In coexistence with that the most severe impairment was found on the phonemic verbal fluency task measuring frontal executive functions.


Subject(s)
Cognition Disorders/etiology , Cognition Disorders/pathology , Corpus Striatum/pathology , Dyskinesias/etiology , Executive Function , Frontal Lobe/pathology , Hyperglycemia/complications , Speech Disorders/etiology , Abetalipoproteinemia/etiology , Abetalipoproteinemia/pathology , Adult , Caudate Nucleus/pathology , Diabetes Complications/pathology , Dyskinesias/pathology , Humans , Hyperglycemia/pathology , Magnetic Resonance Imaging , Male , Memory, Short-Term , Putamen/pathology , Speech Disorders/pathology
3.
J Med Case Rep ; 8: 390, 2014 Nov 27.
Article in English | MEDLINE | ID: mdl-25427442

ABSTRACT

INTRODUCTION: Klippel-Trenaunay syndrome is a rare congenital mesodermal abnormality characterized by bone and soft tissue hypertrophy, extensive hemangioma and venous abnormalities. We report the case of a patient with two additional rare clinical manifestations in the background of Klippel-Trenaunay syndrome, namely, acanthocytosis and splenic and retroperitoneal lymphangioma. CASE PRESENTATION: A 24-year-old Sri Lankan man from North Central Province in Sri Lanka presented to our general medical unit with symptomatic anaemia. He had been diagnosed with Klippel-Trenaunay syndrome at the age of six years, with hemihypertrophy of his right lower limb and strawberry naevi over both lower limbs. His blood film results were positive for acanthocytes, which accounted for more than 20% of the red blood cell population. He was also found to have extensive splenic lymphangiomas and a large retroperitoneal lymphangioma encasing the mesentric vessels in the right para-aortic region. An extensive battery of tests to identify a secondary cause for the acanthocytosis failed to show any positive results. CONCLUSIONS: Retroperitoneal lymphangioma has been reported in association with Klippel-Trenaunay syndrome once before, but an association with acanthocytosis has never been reported. Given the rarity of all three conditions this is not surprising. The cause of acanthocytosis in this setting is currently unresolved. It is plausible that this may be a primary association with Klippel-Trenaunay syndrome, as an alternative aetiology was not found.


Subject(s)
Abetalipoproteinemia/etiology , Klippel-Trenaunay-Weber Syndrome/complications , Lymphangioma/etiology , Retroperitoneal Neoplasms/etiology , Splenic Neoplasms/etiology , Humans , Klippel-Trenaunay-Weber Syndrome/diagnosis , Lymphangioma/diagnosis , Lymphangioma/pathology , Male , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/pathology , Spleen/pathology , Splenic Neoplasms/diagnosis , Splenic Neoplasms/diagnostic imaging , Splenic Neoplasms/pathology , Tomography, X-Ray Computed , Young Adult
4.
Handb Clin Neurol ; 113: 1799-810, 2013.
Article in English | MEDLINE | ID: mdl-23622402

ABSTRACT

The catalytic properties of many enzymes depend on the participation of vitamins as obligatory cofactors. Vitamin B12 (cobalamin) and folic acid (folate) deficiencies in infants and children classically present with megaloblastic anemia and are often accompanied by neurological signs. A number of rare inborn errors of cobalamin and folate absorption, transport, cellular uptake, and intracellular metabolism have been delineated and identification of disease-causing mutations has improved our ability to diagnose and treat many of these conditions. Two inherited defects in biotin metabolism are known, holocarboxylase synthetase and biotinidase deficiency. Both lead to multiple carboxylase deficiency manifesting with metabolic acidosis, neurological abnormalities, and skin rash. Thiamine-responsive megaloblastic anemia is characterized by megaloblastic anemia, non-type I diabetes, and sensorineural deafness that responds to pharmacological doses of thiamine (vitamin B1). Individuals affected with inherited vitamin E deficiencies including ataxia with isolated vitamin E deficiency and abetalipoproteinemia present with a spinocerebellar syndrome similar to patients with Friedreich's ataxia. If started early, treatment of these defects by oral or parenteral administration of the relevant vitamin often results in correction of the metabolic defect and reversal of the signs of disease, stressing the importance of early and correct diagnosis in these treatable conditions.


Subject(s)
Abetalipoproteinemia/diagnosis , Ataxia/diagnosis , Biotinidase Deficiency/diagnosis , Folic Acid Deficiency/diagnosis , Thiamine Deficiency/diagnosis , Vitamin B 12 Deficiency/diagnosis , Vitamin E Deficiency/diagnosis , Vitamins/therapeutic use , Abetalipoproteinemia/drug therapy , Abetalipoproteinemia/etiology , Ataxia/drug therapy , Ataxia/etiology , Biotinidase Deficiency/drug therapy , Biotinidase Deficiency/etiology , Child , Folic Acid Deficiency/drug therapy , Folic Acid Deficiency/etiology , Humans , Thiamine Deficiency/drug therapy , Thiamine Deficiency/etiology , Vitamin B 12 Deficiency/drug therapy , Vitamin B 12 Deficiency/etiology , Vitamin E Deficiency/drug therapy , Vitamin E Deficiency/etiology
6.
Am J Med Sci ; 324(5): 281-4, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12449451

ABSTRACT

We report the case of a 17-year-old woman with anorexia nervosa (AN) who developed an abetalipoproteinemia-like lipid profile and acanthocytosis. These abnormalities resolved slowly as her nutritional status improved. We considered 3 possible causes of an abetalipoproteinemia-like lipid profile in AN: (1) depletion of hepatic substrate for apolipoprotein B synthesis, (2) lack of exogenous fatty acids with exhaustion of endogenous stores of triglycerides in adipose tissue, and (3) preservation of the lipoprotein lipase (LPL) mass. This unusual case provides important clues that enhance our understanding of lipid metabolism under exogenous and endogenous fat deprivation and highlights the pivotal role of LPL as a gatekeeper of the energy source.


Subject(s)
Abetalipoproteinemia/diagnosis , Abetalipoproteinemia/etiology , Acanthocytes , Anorexia Nervosa/complications , Anorexia Nervosa/diagnosis , Acanthocytes/pathology , Adolescent , Anemia/etiology , Anorexia Nervosa/pathology , Anorexia Nervosa/therapy , Body Weight , Diagnosis, Differential , Female , Humans , Length of Stay , Nutrition Disorders/etiology , Nutritional Status , Parenteral Nutrition, Total , Psychotherapy , Thrombocytopenia/etiology , Treatment Outcome
14.
J Biol Chem ; 270(24): 14281-5, 1995 Jun 16.
Article in English | MEDLINE | ID: mdl-7782284

ABSTRACT

The microsomal triglyceride transfer protein (MTP) is a heterodimer composed of the multifunctional enzyme, protein disulfide-isomerase, and a unique large, 97 kDa, subunit. It is found as a soluble protein within the lumen of the endoplasmic reticulum of liver and intestine and is required for the assembly of very low density lipoproteins and chylomicrons. Mutations in MTP which result in an absence of MTP function have been shown to cause abetalipoproteinemia. Here, the gene encoding the MTP 97-kDa subunit of an abetalipoproteinemic subject, which we have previously demonstrated lacks MTP activity and protein (Wetterau, J. R., Aggerbeck, L. P., Bouma, M.-E., Eisenberg, C., Munck, A., Hermier, M., Schmitz, J., Gay, G., Rader, D. J., and Gregg, R. E. (1992) Science 258, 999-1001), was isolated and sequenced. A nonsense mutation, which predicts the truncation of the protein by 30 amino acids, was identified. To investigate if this apparently subtle change in MTP could explain the observed absence of MTP, protein disulfide-isomerase was co-expressed with either the normal or mutant MTP 97-kDa subunit in Sf9 insect cells using a baculovirus expression system. Although there were high levels of expression of both the normal and mutant forms of the MTP 97-kDa subunit, only the normal subunit was able to form a stable, soluble complex with protein disulfide-isomerase. These results indicate that the carboxyl-terminal 30 amino acids of the MTP 97-kDa subunit plays an important role in its interaction with protein disulfide-isomerase.


Subject(s)
Abetalipoproteinemia/metabolism , Carrier Proteins/metabolism , Glycoproteins , Isomerases/metabolism , Triglycerides/metabolism , Abetalipoproteinemia/etiology , Base Sequence , Carrier Proteins/chemistry , Carrier Proteins/genetics , Cell Line , Cholesterol Ester Transfer Proteins , DNA Primers , Humans , Male , Middle Aged , Molecular Sequence Data , Mutation , Nucleopolyhedroviruses/genetics , Protein Disulfide-Isomerases , Structure-Activity Relationship
15.
JAMA ; 270(7): 865-9, 1993 Aug 18.
Article in English | MEDLINE | ID: mdl-8340987

ABSTRACT

Abetalipoproteinemia is a rare genetic disease that has provided important new insights into the physiology of lipoprotein assembly and vitamin E metabolism. Forty-two years after its initial description, a molecular etiology of ABL has been reported to be a deficiency of a microsomal transfer protein, thus suggesting that this protein plays a key role in lipoprotein particle assembly and secretion both in the intestine and in the liver. Furthermore, studies in patients with ABL have established the critical role of hepatic secretion of VLDL in the delivery of vitamin E to peripheral tissues and the essential role of vitamin E in the maintenance of normal physiological function of multiple tissues. The systematic investigation of this rare genetic disease has provided insights that have substantially enhanced our understanding of human physiology.


Subject(s)
Abetalipoproteinemia , Abetalipoproteinemia/diagnosis , Abetalipoproteinemia/etiology , Abetalipoproteinemia/metabolism , Abetalipoproteinemia/physiopathology , Abetalipoproteinemia/therapy , Adult , Female , Humans , Lipoproteins/metabolism , Vitamin E/metabolism
16.
J Biochem ; 113(6): 786-9, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8370676

ABSTRACT

We have previously reported that fatty liver was induced in a novel experimental animal, Suncus murinus (suncus), by 24-h fasting and that apolipoprotein B (apo B) was not actively synthesized in the liver. However, a faint signal of apo B mRNA was detected in the liver, suggesting possible synthesis of apo B. Small amounts of VLDL and LDL have been separated from suncus serum by ultracentrifugation. Electron microscopic study of the lipoproteins revealed the existence of small particles in VLDL. High performance liquid chromatographic analysis of the lipoproteins showed that the peaks of TG and cholesterol were mainly at the HDL fraction. These results indicate the existence of lipoproteins as small as HDL which were rich in TG and floated at the density of VLDL upon ultracentrifugation. Apolipoprotein analysis showed two bands of 500- and 200-kDa proteins in VLDL and LDL. Western blot analysis using antibody against the 500-kDa protein revealed reaction not only with suncus 500- and 200-kDa proteins but also with human apo B-100. In conclusion, a small amount of apo B is transported in the suncus serum as VLDL and LDL, although almost all lipid is packed in HDL-size particles.


Subject(s)
Abetalipoproteinemia/etiology , Lipoproteins/blood , Shrews/blood , Abetalipoproteinemia/metabolism , Animals , Apolipoproteins/blood , Apolipoproteins B/blood , Apolipoproteins B/metabolism , Disease Models, Animal , Lipoproteins/metabolism , Liver/metabolism , Microscopy, Electron , Shrews/metabolism , Species Specificity
17.
Science ; 258(5084): 999-1001, 1992 Nov 06.
Article in English | MEDLINE | ID: mdl-1439810

ABSTRACT

Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects. This finding suggests that a defect in MTP is the basis for abetalipoproteinemia and that MTP is indeed required for lipoprotein assembly.


Subject(s)
Abetalipoproteinemia/etiology , Intestines/chemistry , Chylomicrons/metabolism , Duodenum/chemistry , Duodenum/metabolism , Duodenum/ultrastructure , Humans , Immunoblotting , Intestines/ultrastructure , Jejunum/chemistry , Jejunum/metabolism , Jejunum/ultrastructure , Lipoproteins, VLDL/biosynthesis , Microsomes/chemistry , Microsomes/metabolism , Microsomes, Liver/chemistry , Triglycerides/metabolism
18.
Bull Clin Neurosci ; 50: 53-60, 1985.
Article in English | MEDLINE | ID: mdl-3915952

ABSTRACT

A well-defined degenerative neurological condition has been associated with cholestatic liver disease in children. This syndrome, heralded by gait and limb ataxia, areflexia, and proprioceptive and vibratory sensory loss, has also been observed in abetalipoproteinemia (Bassen-Kornzweig syndrome), cystic fibrosis, and intestinal malabsorption states. A significant body of evidence suggests that vitamin E (alpha-tocopherol) deficiency is in large part responsible for this condition. In this article, a patient manifesting this syndrome is reported, and the current status of the vitamin E deficiency state is reviewed.


Subject(s)
Abetalipoproteinemia/etiology , Vitamin E Deficiency/complications , Abetalipoproteinemia/genetics , Abetalipoproteinemia/pathology , Adult , Humans , Male , Vitamin E Deficiency/metabolism
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