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

Amino Acid Metabolism, Inborn Errors ; etiology ; therapy ; Glutarates ; blood ; Humans ; Infant, Newborn ; Male

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

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder. This paper reports three cases of SSADH deficiency in infants. The infants developed the symptoms including developmental delay, intellectual disability, hypotonia, hyporeflexia and seizures. The electroencephalogram (EEG) showed background slowing and focal spike discharges in all of 3 patients. Head magnetic resonance imaging (MRI) demonstrated abnormalities in 2 patients, including basal ganglia damage and increased T2-weighted signal in bilateral cerebral peduncles. Urinary organic acid analysis with gas chromatography-mass spectrometry (GC-MS) revealed increased levels of 4-hydroxybutyrate (GHB) in 3 patients. SSADH deficiency was definitely diagnosed based on the clinical manifestations and the results of urinary organic acid analysis in the 3 children. It was concluded that early urine organic acid analysis is essential for children presenting with mental retardation, neuropsychiatric disturbance or epilepsy of unknown etiology.
Amino Acid Metabolism, Inborn Errors ; diagnosis ; therapy ; Developmental Disabilities ; Diagnosis, Differential ; Female ; Humans ; Infant ; Succinate-Semialdehyde Dehydrogenase ; deficiency

Rapid ammonia elevation in blood with accompanying mental change should be considered as a true medical emergency. In such a case, action leading to immediate diagnosis and the earliest possible treatment must occur in order to minimize permanent brain damage. Hyperornithinemia- Hyperammonemia-Homocitrullinuria (HHH) syndrome is a rare inborn errors of metabolism and autosomal recessive metabolic disorder caused by a deficiency of the mitochondrial ornithine transporter at the cellular level. Emergency physicians should take account of the possibility of HHH syndrome in patients with unreasonable hyperammonemia coupled with altered mental status. We report a case of a 59-year old man who presented with headache, nausea, vomiting and altered mental status. His serologic test showed hyperornithinemia, hyperammomemia, and homocitrullinuria. He was treated with fluid therapy and hemodialysis. His clinical manifestation improved and he was discharged after hemodialysis
Amino Acid Transport Systems, Basic ; Ammonia ; Brain ; Emergencies ; Fluid Therapy ; Headache ; Humans ; Hyperammonemia ; Metabolism, Inborn Errors ; Nausea ; Ornithine ; Renal Dialysis ; Serologic Tests ; Urea Cycle Disorders, Inborn ; Vomiting

Amino Acid Metabolism, Inborn Errors ; diagnosis ; metabolism ; therapy ; Diagnosis, Differential ; Diet ; Glutarates ; metabolism ; urine ; Humans ; Infant ; Male ; Riboflavin ; therapeutic use ; Treatment Outcome

Parainfluenza virus infection is one of the causes of fatal rhabdomyolysis. Rhabdomyolysis can be aggravated by mitochondrial fatty acid beta-oxidation disorders during prolonged periods of fasting. Moreover, in patients with late-onset isovaleric acidemia, hyperammonemia may occur following catabolic stress. In the present report, we describe a case of a 4-year-old boy with parainfluenza virus infection and late-onset isovaleric acidemia that rapidly progressed to coma, seizures, and cardiorespiratory collapse. His serum ammonia and creatinine kinase (CK) levels were 385 microMol/L and 23,707 IU/L, respectively. Continuous renal replacement therapy (CRRT) was initiated using continuous venovenous hemodiafiltration, after which the ammonia and CK levels returned to normal. Thus, we recommend the immediate initiation of CRRT in the management of patients with life-threatening rhabdomyolysis and hyperammonemia.
Amino Acid Metabolism, Inborn Errors ; Ammonia ; Child* ; Coma ; Creatinine ; Fasting ; Hemodiafiltration ; Humans ; Hyperammonemia* ; Isovaleryl-CoA Dehydrogenase ; Male ; Paramyxoviridae Infections* ; Phosphotransferases ; Preschool Child* ; Renal Replacement Therapy* ; Rhabdomyolysis* ; Seizures

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

OBJECTIVETo explore the clinical feature, therapeutic effect and prognosis of isolated methylmalonic acidemia.

METHODSThe clinical characteristics, laboratory findings, treatment and outcome of 40 patients were retrospectively analyzed. The main treatment was a low-protein diet supplemented with L-carnitine and special milk free of leucine, valine, threonine and methionine. Vitamin B12 was also given to cobalamin responders. The patients were followed up every 1-3 months.

RESULTSMutations in the MUT gene were identified in 30 of 33 patients who had accepted DNA testing. Thirty cases were treated and followed up regularly for from 1 month to 8 years. Eight cases had died, 8 had developed normal intelligence, among whom 4 from newborn screening were asymptomatic. Psychomotor developmental delay and mental retardation were present in 14 cases. The propionylcarnitine level, ratio of propionylcarnitine/acetylcarnitine in blood, methylmalonic acid and methylcitric acid levels in urine have decreased significantly, with the median values reduced respectively from 24.15 (7.92-81.02) μmol/L, 1.08 (0.38-6.01), 705.34 (113.79-3078.60) and 7.71 (0.52-128.21) to 10.50 (3.00-30.92) μmol/L, 0.63 (0.25-2.89), 166.23 (22.40-3322.21) and 3.96 (0.94-119.13) (P < 0.05).

CONCLUSIONThe prognosis of isolated methylmalonic acidemia may be predicted with the enzymatic subgroup, age at onset and cobalamin responsiveness. Outcome is unfavorable in neonatal patients and those who were non-responsive to cobalamin.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; diet therapy ; enzymology ; metabolism ; Carnitine ; metabolism ; Child ; Child, Preschool ; Diet, Protein-Restricted ; utilization ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Male ; Methylmalonyl-CoA Mutase ; genetics ; Retrospective Studies

Amino Acid Metabolism, Inborn Errors ; diagnosis ; genetics ; therapy ; Death, Sudden ; etiology ; Hereditary Central Nervous System Demyelinating Diseases ; diagnosis ; etiology ; Humans ; Hydroxymethylglutaryl-CoA Synthase ; deficiency ; Infant, Newborn ; Male ; Mutation ; Oxo-Acid-Lyases ; genetics ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry