Sphingolipidoses are a subgroup of lysosomal storage disorders. They are characterized by relentless progressive storage in affected organs and concomitant functional impairments. No overall screening procedure for these disorders is available. Their course and appearance, however, are usually characteristic and, together with relevant technical procedures such as magnetic resonance imaging (MRI), clinical neurophysiology, ophthalmologic examination, etc., a provisional diagnosis can be made, after which enzymatic diagnosis can close the gap in the diagnostic process. Subgroups of sphingolipidoses are grouped together, such as disorders with prominent hepatosplenomegaly (Niemann-Pick A, B and Gaucher disease) and disorders with central and peripheral demyelination (metachromic leukodystrophy and Krabbe disease). Farber disease and Fabry disease are unique in themselves. The last decade has seen hopeful progress in therapeutic strategies, especially for Gaucher disease. Therefore, emphasis of this review has been placed on these new developments.
Demyelinating Diseases ; Diagnosis ; Fabry Disease ; Farber Lipogranulomatosis ; Gangliosidoses, GM2 ; Gangliosidosis, GM1 ; Gaucher Disease ; Hope ; Leukodystrophy, Globoid Cell ; Magnetic Resonance Imaging ; Mass Screening ; Neurophysiology ; Niemann-Pick Diseases ; Sphingolipidoses*

Animals ; Apolipoproteins E ; deficiency ; Female ; Hyperlipoproteinemia Type III ; blood ; metabolism ; Lipid Metabolism, Inborn Errors ; blood ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Calcitriol ; metabolism ; Vitamin D ; blood

Adolescent ; Female ; Humans ; Lipid Metabolism, Inborn Errors ; diagnosis ; therapy ; Muscular Diseases ; diagnosis ; therapy

OBJECTIVE: To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). METHODS: Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES). RESULTS: All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant. CONCLUSION The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.
Child ; Humans ; Acyl-CoA Dehydrogenase/genetics* ; Carnitine ; Genetic Testing ; Lipid Metabolism, Inborn Errors/genetics* ; Neonatal Screening

OBJECTIVEMany inborn errors of metabolism have similar presenting clinical manifestations, making early diagnosis difficult. We report our experience with tandem mass spectrometry combined with urine gas chromatography/mass spectrometry as a means of definitively diagnosing inborn errors of metabolism.

METHODSOne hundred and thirty-two children with suspected inborn errors of metabolism but without specific clinical manifestations, admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between June 1, 2003 and September 30, 2006, were studied. Children received routine biochemical examinations, as well as mass spectrometry and gas chromatography-mass spectrometry.

RESULTSFifteen cases (11.5%) were confirmed as having inborn errors of metabolism, including 6 cases of methylmalonic acidemia, 2 of propionic academia, 2 of Type II citrullinemia, 1 of biotinidase deficiency, 1 of tyrosinemia, 1 of maple syrup urine disease, 1 of omithine transcarbamylase deficiency and 1 of very long chain Acyl CoA dehydrogenase deficiency.

CONCLUSIONSThe combined use of tandem mass spectrometry with urine gas chromatography mass spectrometry is useful for early diagnosis of inborn errors of metabolism in children with suspected inborn errors of metabolism but without specific clinical manifestations.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; Child ; Child, Preschool ; Female ; Gas Chromatography-Mass Spectrometry ; methods ; Humans ; Infant ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; diagnosis ; Male ; Metabolism, Inborn Errors ; diagnosis ; urine ; Tandem Mass Spectrometry ; methods

OBJECTIVETo screen and diagnose fatty acid oxidation disorders (FAOD) in high risk children with inborn error of metabolism using tandem mass spectrometry.

METHODSThe study group consisting of 2941 high risk cases of suspected inborn error of metabolism was tested. The acylcarnitines in the dry blood filter papers of patients were tested by tandem mass spectrometry. The diagnosis of FAOD was according to the levels of the acylcarnitines, the clinical symptoms, and other biochemistry study.

RESULTSFourteen patients were diagnosed as FAOD. These patients included one carnitine palmitoyltransferase deficiency I, one carnitine palmitoyltransferase deficiency II, one short-chain acyl-CoA dehydrogenase deficiency, seven medium-chain acyl-CoA dehydrogenase deficiency, two very long-chain acyl-CoA dehydrogenase deficiency, and two multiple acyl-CoA dehydrogenase deficiency.

CONCLUSIONFAOD are not rare in China. Analysis of acylcarnitines levels tested by tandem mass spectrometry is helpful to diagnose FAOD.

Adolescent ; Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; Carnitine ; analogs & derivatives ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Lipid Metabolism ; physiology ; Lipid Metabolism, Inborn Errors ; diagnosis ; Male ; Mass Spectrometry ; Tandem Mass Spectrometry ; methods

Humans ; Muscular Diseases/genetics* ; Cardiomyopathies/genetics* ; Lipid Metabolism, Inborn Errors/genetics* ; Mutation ; Lipids ; Muscle, Skeletal ; Acyltransferases/genetics* ; Lipase/genetics*

OBJECTIVE: To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency. METHODS: Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS). RESULTS: Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father. CONCLUSION CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.
Carnitine/blood* ; Carnitine O-Palmitoyltransferase/genetics* ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/genetics* ; Lipid Metabolism, Inborn Errors/genetics*

BACKGROUND AND OBJECTIVES: Adiponectin is an adipose tissue-derived hormone that has beneficial effects on cardiac function and has been reported to be associated with lipid metabolism, glucose metabolism, and insulin resistance. Serum levels of adiponectin are reduced in obese individuals compared with non-obese individuals. Obesity is associated with an increased incidence of atrial fibrillation (AF); however, the role of adiponectin in AF is unclear. The aim of this study is to evaluate the relationship between the plasma adiponectin level and AF. SUBJECTS AND METHODS: Sixty-one consecutive patients were prospectively enrolled for this study. Subjects were divided into two groups: patients with AF (n=30) and controls (n=31). Laboratory evaluation, including levels of plasma adiponectin, was performed and echocardiographic parameters were measured. RESULTS: The baseline characteristics were not different between the two groups. The plasma adiponectin level of patients in the AF group was significantly lower than in the control group (14.9+/-7.2 vs. 19.+/-8.9 microg/mL, p<0.05). In addition, when we divided the AF patients into paroxysmal and chronic AF, the plasma adiponectin level was significantly lower in patients with paroxysmal AF, compared with the control group. In multiple binary logistic regression analysis to evaluate the independent predictors for AF, adiponectin and left atrial diameter were strong independent predictors of AF. CONCLUSION: In this study a lower plasma adiponectin concentration was significantly associated with that of paroxysmal AF. Hypoadiponectinemia can potentially be an important risk factor for AF.
Adiponectin ; Atrial Fibrillation ; Glucose ; Humans ; Incidence ; Insulin Resistance ; Lipid Metabolism ; Logistic Models ; Metabolism, Inborn Errors ; Obesity ; Plasma ; Prospective Studies ; Risk Factors

A 32-year-old female patient and her sister show high levels of high density lipoprotein (HDL) cholesterol in regular health checkups, since female patient was 11 years old. The patient's serum total cholesterol was 285 mg/dL and HDL cholesterol was 113 mg/dL. Her sister's total cholesterol was 240 mg/dL and the HDL cholesterol measured to be 90 mg/dL. Lipoprotein pattern and cholesteryl ester transfer activity gene analysis were examined in these patients. We found c.1321+1G>A (IVS14+1G/A) hetero mutation in cholesteryl ester transfer protein (CETP) genes. Generally, CETP mediates transfer and exchange of triglycerides and cholesteryl ester between plasma lipoproteins. Also we investigated a key role of HDL-CE and Apo A-1 metabolism. Patients with low levels of CETP have increased serum HDL levels. We hereby report two Korean cases of CETP deficiency in a family. Brief literature review ensues with the cases.
Adult ; Apolipoprotein A-I ; Cholesterol ; Cholesterol Ester Transfer Proteins ; Cholesterol, HDL ; Female ; Humans ; Hypercholesterolemia ; Lipid Metabolism, Inborn Errors ; Lipoproteins ; Plasma ; Protein Deficiency ; Siblings ; Triglycerides