OBJECTIVES: To summarize the clinical characteristics and nutrition therapy for children with lysinuric protein intolerance (LPI). METHODS: The clinical manifestations, laboratory test results and enteral nutrition treatment in a girl with LPI diagnosed in Xiangya Hospital, Central South University were retrospective analyzed. Additionally, the data of the children with LPI reported in China and overseas were reviewed. RESULTS: A case of 4-year-old girl was presented, who exhibited significant gastrointestinal symptoms, such as chronic abdominal distension, prolonged diarrhea, recurrent pneumonia, and limited growth. She had a poor response to anti-infection treatment. After receiving enteral nutrition therapy, she did not experience any gastrointestinal discomfort, and there were improvements in the levels of hemoglobin, albumin, and blood ammonia. Unfortunately, due to serious illness, she declined further treatment and later passed away. A total of 92 cases of pediatric patients with LPI have been reported to date, including one case reported in this study. Most children with LPI experienced disease onset after weaning or introduction of complementary foods, presenting with severe digestive system symptoms, malnutrition, and growth retardation. It is noteworthy that only 50% (46/92) of these cases received nutritional therapy, which effectively improved their nutritional status. Among the 92 children, 8 (9%) died, and long-term follow-up data were lacking in other reports. CONCLUSIONS LPI often involves the digestive system and may result in growth restriction with a poor prognosis. Nutritional therapy plays a crucial role in the comprehensive treatment of LPI.
Child, Preschool ; Female ; Humans ; Amino Acid Metabolism, Inborn Errors/therapy* ; Enteral Nutrition/methods* ; Malnutrition ; Retrospective Studies

Pediatric liver transplantation (PLT) is an effective strategy of treating various acute or chronic end-stage liver diseases and inherited metabolic diseases in children.PLT has been applied in many transplant centers nationwide and has achieved satisfactory results.However,the development of transplant centers is uneven,and there is a lack of consensus and standards within the industry.In order to reduce post-operative complications,accelerate post-operative recovery,and improve the short-and long-term quality of life of children,the Enhanced Recovery After Surgery Committee of Chinese Research Hospital Association organized multidisciplinary experts to summarize the progress of domestic and international research,and formulated a perioperative consensus on PLT based on the principles of evidence-based medicine.The consensus provides recommendations for perioperative PLT from three aspects:preoperative assessment and preparation,intraoperative management and postoperative management,in order to provide reference guidelines for centers that are conducting or preparing to conduct PLT.
Child ; Consensus ; End Stage Liver Disease/therapy* ; Enhanced Recovery After Surgery/standards* ; Humans ; Liver Transplantation/standards* ; Metabolism, Inborn Errors/therapy* ; Perioperative Care/standards* ; Practice Guidelines as Topic

Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates
Ammonia ; Astrocytes ; Brain Edema ; Coma ; Diagnosis ; Edema ; Emergency Treatment ; Humans ; Hyperammonemia ; Infant, Newborn ; Metabolism ; Metabolism, Inborn Errors ; Peritoneal Dialysis ; Plasma ; Prescriptions ; Prognosis ; Renal Dialysis ; Renal Replacement Therapy ; Urea

OBJECTIVETo investigate the clinical features, diagnosis and treatment of glucose transporter 1 deficiency syndrome (GLUT1-DS), as well as the diagnostic value of movement disorders.

METHODSThe clinical data of four children with GLUT1-DS were collected, and their clinical features, treatment, and follow-up results were analyzed.

RESULTSThere were two boys and two girls, with an age of onset of 2-15 months. Clinical manifestations included movement disorders, seizures, and developmental retardation. Seizures were the cause of the first consultation in all cases. The four children all had persistent ataxia, dystonia, and dysarthria; two had persistent tremor, two had paroxysmal limb paralysis, and two had eye movement disorders. Paroxysmal symptoms tended to occur in fatigue state. All four children had reductions in the level of cerebrospinal fluid glucose and its ratio to blood glucose, as well as SLC2A1 gene mutations. The four children were given a ketogenic diet, at a ketogenic ratio of 2:1 to 3:1, and achieved complete remission of paroxysmal symptoms within 5 weeks.

CONCLUSIONSGLUT1-DS should be considered for epileptic children with mental retardation and motor developmental delay complicated by various types of movement disorders. The ketogenic diet is effective at a ketogenic ratio of 2:1 to 3:1 for the treatment of GLUT1-DS.

Carbohydrate Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Child ; Child, Preschool ; Female ; Humans ; Male ; Monosaccharide Transport Proteins ; deficiency ; genetics ; Movement Disorders ; diagnosis ; genetics ; therapy

OBJECTIVETo investigate the effect of glutaryl-CoA dehydrogenase (GCDH) gene silencing and accumulation of lysine metabolites on the viability of hepatocytes.

METHODSBRL cells were divided into normal control group, negative control group, and GCDH silencing group. The shRNA lentiviral vector for silencing GCDH gene was constructed, and the BRL hepatocytes in the GCDH silencing group and the negative control group were infected with this lentivirus and negative control virus respectively, and then cultured in a medium containing 5 mmol/L lysine. Immunofluorescence assay was used to measure the infection efficiency of lentivirus. Western blot was used to measure the expression of GCDH protein. MTT assay was used to evaluate cell viability. Hoechest33342 staining was used to measure cell apoptosis. Western blot was used to measure the expression of Caspase-3, an index of cell apoptosis.

RESULTSThe lentivirus constructed effectively silenced the GCDH gene in hepatocytes (P<0.01). MTT assay and Hoechest 33342 staining showed no significant differences in cell viability and apoptosis between groups (P>0.05). There was also no significant difference in the expression of Caspase-3 protein between groups (P>0.05).

CONCLUSIONSGCDH gene silencing and accumulation of lysine metabolites may not cause marked hepatocyte injury.

Amino Acid Metabolism, Inborn Errors ; pathology ; therapy ; Animals ; Apoptosis ; Brain Diseases, Metabolic ; pathology ; therapy ; Caspase 3 ; metabolism ; Cell Survival ; Cells, Cultured ; Fluorescent Antibody Technique ; Gene Silencing ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Hepatocytes ; pathology ; Lysine ; metabolism ; Rats

Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges.
Bile Acids and Salts ; blood ; Cholestasis ; blood ; genetics ; physiopathology ; therapy ; Humans ; Infant ; Liver ; physiopathology ; Male ; Mutation ; Oxidoreductases ; blood ; deficiency ; genetics ; Steroid Metabolism, Inborn Errors ; blood ; genetics ; physiopathology ; therapy

BACKGROUNDLate-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common type of lipid storage myopathies in China. Most patients with late-onset MADD are well responsive to riboflavin. Up to now, these patients are often treated with glucocorticoids as the first-line drug because they are misdiagnosed as polymyositis without muscle biopsy or gene analysis. Although glucocorticoids seem to improve the fatty acid metabolism of late-onset MADD, the objective evaluation of their rationalization on this disorder and comparison with riboflavin treatment are unknown.

METHODSWe performed a historical cohort study on the efficacy of the two drugs among 45 patients with late-onset MADD, who were divided into glucocorticoids group and riboflavin group. Detailed clinical information of baseline and 1-month follow-up were collected.

RESULTSAfter 1-month treatment, a dramatic improvement of muscle strength was found in riboflavin group (P < 0.05). There was no significant difference in muscle enzymes between the two groups. Significantly, the number of patients with full recovery in glucocorticoids group was less than the number in riboflavin group (P < 0.05). On the other hand, almost half of the patients in riboflavin group still presented high-level muscle enzymes and weak muscle strength after 1-month riboflavin treatment, meaning that 1-month treatment duration maybe insufficient and patients should keep on riboflavin supplement for a longer time.

CONCLUSIONSOur results provide credible evidences that the overall efficacy of riboflavin is superior to glucocorticoids, and a longer duration of riboflavin treatment is necessary for patients with late-onset MADD.

Adolescent ; Adult ; Age of Onset ; Child ; Cohort Studies ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Lipid Metabolism, Inborn Errors ; therapy ; Male ; Multiple Acyl Coenzyme A Dehydrogenase Deficiency ; drug therapy ; Muscular Dystrophies ; therapy ; Riboflavin ; therapeutic use ; Young Adult

Glutaric aciduria type 1 is a rare autosomal recessive disorder. GCDH gene mutations cause glutaryl-CoA dehydrogenase deficiency and accumulation of glutaric acid and 3-hydroxyglutaric acid, resulting in damage of striatum and other brain nucleus and neurodegeneration. Patients with glutaric aciduria type 1 present with complex heterogeneous phenotypes and genotypes. The symptoms are extremely variable. The ages of the clinical onset of the patients range from the fetus period to adulthood. The patients with mild glutaric aciduria type 1 are almost asymptomatic before onset, however, severe glutaric aciduria type 1 may cause death or disability due to acute encephalopathy. Acute metabolic crisis in patients with underlying glutaric aciduria type 1 is often triggered by febrile illnesses, trauma, hunger, high-protein foods and vaccination during a vulnerable period of brain development in infancy or early childhood. The early-onset patients usually have a poor prognosis. Urinary organic acids analysis, blood acylcarnitines analysis and GCDH study are important for the diagnosis of this disorder. Neonatal screening is essential for the early diagnosis and the improvement of prognosis.
Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Brain Diseases, Metabolic ; diagnosis ; genetics ; therapy ; Genotype ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Humans ; Infant, Newborn ; Neonatal Screening ; Phenotype ; Prenatal Diagnosis ; Prognosis

Amino Acid Metabolism, Inborn Errors ; complications ; therapy ; Anemia, Macrocytic ; etiology ; Humans ; Infant ; Male

Hematopoietic stem cell transplantation (HSCT) is the first field where human stem cell therapy was successful. Flooding interest on human stem cell therapy to cure previously incurable diseases is largely indebted to HSCT success. Allogeneic HSCT has been an important modality to cure various diseases including hematologic malignancies, various non-malignant hematologic diseases, primary immunodeficiency diseases, and inborn errors of metabolism, while autologous HSCT is generally performed to rescue bone marrow aplasia following high-dose chemotherapy for solid tumors or multiple myeloma. Recently, HSCs are also spotlighted in the field of regenerative medicine for the amelioration of symptoms caused by neurodegenerative diseases, heart diseases, and others. Although the demand for HSCs has been growing, their supply often fails to meet the demand of the patients needing transplant due to a lack of histocompatible donors or a limited cell number. This review focuses on the generation and large-scale expansion of HSCs, which might overcome current limitations in the application of HSCs for clinical use. Furthermore, current proof of concept to replenish hematological homeostasis from non-hematological origin will be covered.
Bone Marrow ; Cell Count ; Drug Therapy ; Heart Diseases ; Hematologic Diseases ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells* ; Homeostasis ; Humans ; Metabolism, Inborn Errors ; Multiple Myeloma ; Neurodegenerative Diseases ; Regenerative Medicine ; Stem Cells ; Tissue Donors