Methylmalonic acidemia (MMA) is a series of rare inherited organic acid metabolic disorders with variable and nonspecific clinical manifestations, in particular neurological symptoms such as vomiting, lethargy, etc. Even with timely treatment, patients may still have various degrees of neurological complications and can even die. The prognosis is mainly related to the type of genetic variants, level of metabolites, newborn screening, onset of disease and early initiation of treatment. This article has reviewed the prognosis of patients with various types of MMA and factors that may affect it.
Infant, Newborn ; Humans ; Amino Acid Metabolism, Inborn Errors/complications* ; Prognosis ; Mutation ; Neonatal Screening ; Propionic Acidemia

OBJECTIVE: To assess the value of dry blood spot tandem mass spectrometry for the diagnosis of autism spectrum disorder (ASD). METHODS: Peripheral blood samples of 277 autistic children were collected. Their amino acid and carnitine profiles were detected by liquid chromatography tandem mass spectrometry. Urine samples of suspected patients were collected for verification by gas chromatography mass spectrometry. Blood samples were also taken for genetic testing. RESULTS: Of the 277 children with ASD, 19 (6.9%) were suspected to be with inborn error of metabolism (IEM), which included 6 cases with amino acidemia, 9 with organic acidemia and 4 with fatty acidemia. Three cases of phenylketonuria, one case of homocysteinemia, one case of propionemia, one case of methylmalonic acidemia, one case of glutaric acidemia, one case of isovaleric acidemia, one case of argininemia, one case of citrullinemia I and four cases of primary carnitine deficiency were confirmed by genetic testing, which yielded an overall diagnostic rate of 5.1% (14/277). CONCLUSION Our result has provided further evidence for the co-occurrence of ASD and IEM. Tandem mass spectrometry has a great value for the diagnosis and treatment of ASD in childhood.
Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; Autism Spectrum Disorder ; complications ; diagnosis ; Child ; Dried Blood Spot Testing ; Gas Chromatography-Mass Spectrometry ; Humans ; Metabolism, Inborn Errors ; complications ; diagnosis ; Tandem Mass Spectrometry

OBJECTIVETo explore the value of urine gas chromatography-mass spectrometry (GC-MS) in the screening of children at risk of inherited metabolic diseases (IMD), and to identify the disease spectrum of IMD and the clinical characteristics of children with IMD.

METHODSThe clinical data of 15 851 children at risk of IMD who underwent urine GC-MS in the Tianjin Children's Hospital between February 2012 and December 2016 were retrospectively analyzed.

RESULTSIn the 15 851 children, 5 793 (36.55%) were detected to have metabolic disorders. A total of 117 (0.74%) children were confirmed to have IMD, including 77 cases of methylmalonic acidemia (65.8%). The clinical manifestations of confirmed cases in the neonatal period mainly included jaundice, metabolic acidosis, abnormal muscular tension, feeding difficulty, poor response, and lethargy or coma. The clinical manifestations of confirmed cases in the non-neonatal period mainly included delayed mental and motor development, metabolic acidosis, convulsion, recurrent vomiting, and anemia.

CONCLUSIONSGC-MS is an effective method for the screening for IMD in children at risk. Methylmalonic acidemia is the most common IMD. The clinical manifestations of IMD are different between the confirmed cases in the neonatal and non-neonatal periods.

Acidosis ; etiology ; Adolescent ; Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; Child ; Child, Preschool ; Developmental Disabilities ; etiology ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Infant ; Infant, Newborn ; Male ; Metabolism, Inborn Errors ; complications ; diagnosis ; Retrospective Studies ; Risk

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive hereditary disease and is a congenital metabolic disorder of neurotransmitter biosynthesis. It is mainly manifested as hypotonia, oculogyric crisis, autonomic dysfunction, and developmental delay. This article reports a boy manifested as delayed motor development, hypotonia, and oculogyric crisis. Gene screening for metabolic disorders revealed new compound heterozygous mutations, c.1063dupA (p.I355fs) and c.250A>C (p.S84R), in the exon of DDC gene. The boy had a significant increase in 3-O-methyldopa as measured by dried blood spot. Therefore, he was diagnosed with AADC deficiency. After treatment with the dopamine receptor agonist pramipexole dihydrochloride, the catechol-O-methyltransferase inhibitor entacapone, and vitamin B6, the boy showed mild improvements in hypotonia, blepharoptosis, and oculogyric crisis. Clinical physicians should enhance their ability for identifying AADC deficiency, so as to facilitate early diagnosis and treatment of this disorder. Genetic counseling for birth health and prenatal diagnosis should be performed for parents in need.
Amino Acid Metabolism, Inborn Errors ; complications ; Aromatic-L-Amino-Acid Decarboxylases ; deficiency ; Developmental Disabilities ; etiology ; Feeding and Eating Disorders ; etiology ; Humans ; Infant ; Male ; Nystagmus, Pathologic ; etiology

Amino Acid Metabolism, Inborn Errors ; complications ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male

A one-year-old girl visited the hospital due to limb torsion and developmental regression for one month after hand, foot and mouth disease. At the age of 11 months, she visited a local hospital due to fever for 5 days and skin rash with frequent convulsions for 2 days and was diagnosed with severe hand, foot and mouth disease, viral encephalitis, and status epilepticus. Brain MRI revealed symmetric abnormal signals in the bilateral basal ganglia, bilateral thalamus, cerebral peduncle, bilateral cortex, and hippocampus. She was given immunoglobulin, antiviral drugs, and anticonvulsant drugs for 2 weeks, and the effect was poor. Blood and urine screening for inherited metabolic diseases were performed to clarify the etiology. The analysis of urine organic acids showed significant increases in glutaric acid and 3-hydroxyglutaric acid, which suggested glutaric aciduria type 1, but her blood glutarylcarnitine was normal, and free carnitine significantly decreased. After the treatment with low-lysine diets, L-carnitine, and baclofen for 1 month, the patient showed a significant improvement in symptoms. Hand, foot and mouth disease is a common viral infectious disease in children, and children with underlying diseases such as inherited metabolic diseases and immunodeficiency may experience serious complications. For children with hand, foot and mouth disease and unexplained encephalopathy, inherited metabolic diseases should be considered.
Amino Acid Metabolism, Inborn Errors ; etiology ; Brain Diseases, Metabolic ; etiology ; Developmental Disabilities ; etiology ; Female ; Glutaryl-CoA Dehydrogenase ; deficiency ; Hand, Foot and Mouth Disease ; complications ; Humans ; Infant ; Torsion Abnormality ; etiology

OBJECTIVEWe report the first case of acute encephalopathy induced by vaccination in an infant with methylmalonic aciduria cblA in China.

METHODThe clinical presentation, blood acylcarnitines analysis, urine organic acids analysis and gene studies of the patient were summarized.

RESULTThe proband, a boy, was admitted at the age of 15 months because of recurrent vomiting, acidosis and development delay for 8 months. The previously healthy boy presented vomiting and coma just one hour after hepatitis B vaccination at the age of seven months. Moderate dehydration, electrolyte disturbance and metabolic acidosis had been found. Although his acute metabolic crisis had been corrected soon after intravenous transfusion, psychomotor retardation and recurrent vomiting had been observed. When he was 15 months old, vomiting and lethargy occurred again 3 hours after DTaP vaccination. He was weakened as the illness became worse and got coma with dyspnea 7 days later. He was hospitalized with the suspected diagnosis of viral encephalitis. Blood acylcarnitines analysis, urine organic acids analysis and gene study had been performed for the etiologic investigation.His blood propionylcarnitine (16.3 µmol/L vs. normal range 1.0-5.0 µmol/L) and propionylcarnitine/free carnitine ratio (0.27 vs. normal range 0.03 to 0.25) increased. Markedly elevated urinary methylmalonic acid (388.21 mmol/mol creatinine vs. normal range 0.2 to 3.6 mmol/mol creatinine) and normal plasma total homocysteine supported the diagnosis of isolated methylmalonic aciduria. Two mutations, c.650 T>A (p.L217X) and c.742 C>T (p.Q248X), were identified in his MMAA gene, confirmed the diagnosis of cblA. Each parent carried one of the two mutations. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 2 years and 7 months old with normal development and general condition.

CONCLUSIONA boy with cblA was firstly detected after the acute encephalopathy induced by vaccination in China. It is important to pay more attention to the patients with metabolic crisis or organ damage after vaccination. Metabolic studies are keys to the diagnosis of potential diseases and improve the outcome.

Amino Acid Metabolism, Inborn Errors ; complications ; Brain Diseases ; chemically induced ; Carnitine ; analogs & derivatives ; Diet, Protein-Restricted ; Hepatitis B Vaccines ; adverse effects ; Humans ; Infant ; Male ; Methylmalonic Acid ; urine ; Mutation ; Vaccination ; adverse effects ; Vitamin B Complex ; Vomiting

OBJECTIVETo study the clinical features and treatment outcomes of cardiovascular system involvement in children with methylmalonic aciduria combined with hyperhomocysteinemia (MMACHC).

METHODSThe clinical data of 10 children with methylmalonic aciduria combined with hyperhomocysteinemia and who had cardiovascular system involvement were retrospectively analyzed and the treatment outcomes were followed up.

RESULTSIn the 10 patients, there were 4 cases with initial presentations of cardiovascular system symptoms such as shortness of breath and dyspnea, 3 cases with urinary tract symptoms such as edema, hematuria and proteinuria, and 3 cases with nervous system symptoms such as developmental retardation and convulsions. The 10 patients had different types and severity of cardiovascular injuries. After 3 months to 8 years of follow-up, the congenital heart defects resolved naturally in 2 cases, and the patient with arrhythmia had no obvious changes. In 5 cases of hypertension, blood pressures recovered to normal in 3 cases, and 1 case was lost to follow-up. In 5 patients with pulmonary hypertension, 2 died, 2 recovered, and 1 case had mildly elevated pulmonary artery pressure. Seven patients underwent MMACHC gene testing, and 5 showed c.80A>G mutations.

CONCLUSIONSMetabolic disease should be taken into account for the children with unexplained pulmonary hypertension and hypertension with the onset of the shortness of breath and dyspnea. The severity of cardiovascular system involvement might be one of the most important factors affecting the prognosis of children with MMACHC. Cardiavascular system involvement of the patients may be related to MMACHC c.80A>G mutations.

Amino Acid Metabolism, Inborn Errors ; complications ; genetics ; Cardiovascular Diseases ; etiology ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Hyperhomocysteinemia ; complications ; genetics ; Infant ; Infant, Newborn ; Male ; Retrospective Studies

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

Adolescent ; Amino Acid Metabolism, Inborn Errors ; complications ; Child ; Female ; Humans ; Male ; Mental Disorders ; etiology