OBJECTIVES: To summarize the clinical manifestations and genetic characteristics of creatine deficiency syndrome (CDS) caused by GAMT gene mutations. METHODS: A retrospective analysis was conducted on the clinical and genetic data of two children diagnosed with GAMT deficiency-type CDS at the Children's Medical Center of Xiangya Hospital, Central South University, from December 2020 to December 2024. RESULTS: The two patients presented with symptoms in infancy, and both had compound heterozygous mutations in the GAMT gene. Case 1 exhibited seizures and intellectual disability, while Case 2 had intellectual disability and attention-deficit hyperactivity disorder. Magnetic resonance spectroscopy of cranial MRI in both patients indicated reduced creatine peaks. After creatine treatment, seizures in Case 1 were controlled, but both patients continued to experience intellectual disabilities and behavioral issues. As of December 2024, a total of 21 cases have been reported in China (including this study), and 115 cases have been reported abroad. All patients exhibited developmental delay or intellectual disabilities, with 66.9% (91/136) experiencing seizures, 33.8% (46/136) presenting with motor disorders, and 36.8% (50/136) having behavioral problems. Seventy-five percent (102/136) of patients received creatine treatment, leading to significant improvements in seizures and motor disorders, although cognitive improvement was not substantial. CONCLUSIONS GAMT deficiency-type CDS is rare and presents with nonspecific clinical features. Timely diagnosis facilitates targeted treatment, which can partially improve prognosis.
Child ; Female ; Humans ; Male ; Creatine/deficiency* ; Guanidinoacetate N-Methyltransferase/deficiency* ; Intellectual Disability/genetics* ; Mutation ; Retrospective Studies ; Rhabdomyolysis/genetics* ; Language Development Disorders ; Movement Disorders/congenital*

Background: Leigh syndrome (LS) is a rare disease caused by mitochondrial defects and has high phenotypic and genotypic heterogeneity. We analyzed the clinical symptoms, neuroimaging, muscular histopathology, and genotypes of 13 Chinese LS patients with mitochondrial DNA (mtDNA) mutations. Methods: Mutations in mtDNA were identified by targeted sequencing. The brain imaging features on magnetic resonance imaging (MRI) were analyzed. The levels of lactate in fasting blood and cerebrospinal fluid (CSF) were routinely tested. The levels of urinary organic acids, plasma amino acids, and acylcarnitines were examined with gas chromatography-mass spectrometry and tandem mass spectrometry. The histopathological traits of skeletal muscles were analyzed under microscope. Results: Among 13 patients, mutations of MT-NDs (n = 8) and MT-ATP6 (n = 4) genes were most common. Strabismus (8/13), muscle weakness (8/13), and ataxia (5/13) were also common, especially for the patients with late-onset age after 2 years old. However, respiratory distress was common in patients with early-onset age before 2 years old. The most frequently affected brain area in these patients was the brain stem (12/13), particularly the dorsal part of midbrain, followed by basal ganglia (6/13), thalamus (6/13), cerebellum (5/13), and supratentorial white matter (2/13). Besides, the elevated lactate levels in CSF (6/6) were more common than those in serum (7/13). However, the analysis of abnormal plasma amino acid and urinary organic acid showed limited results (0/3 and 1/4, respectively). Muscular histopathology showed mitochondrial myopathy in the three late-onset patients but not in the early-onset ones. Conclusions Noninvasive genetic screening is recommended for mtDNA mutations in MT-NDs and MT-ATP6 genes in patients with ophthalmoplegia, muscle weakness, ataxia, and respiratory disorder. Furthermore, the lactate detection in CSF and the brain MRI scanning are suggested as the diagnosis methods for LS patients with mtDNA mutations.
Child ; Child, Preschool ; Creatine Kinase ; blood ; Cytochrome-c Oxidase Deficiency ; DNA, Mitochondrial ; genetics ; Fasting ; blood ; cerebrospinal fluid ; Female ; Humans ; Infant ; Lactic Acid ; blood ; cerebrospinal fluid ; Leigh Disease ; diagnostic imaging ; genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; genetics ; Neuroimaging ; methods

Brain ; metabolism ; Brain Chemistry ; Creatine ; deficiency ; Humans ; Syndrome

OBJECTIVETo study the relationship between pathogenesis for Yin-deficiency of acute myocardial infarction (AMI) and immediate prognosis as well as its neuro-endocrine mechanism.

METHODSAccording to the TCM standard of Syndrome Differentiation of Deficiency Syndrome, 194 patients with AMI were classified into the typical Yin-deficiency group (n = 26), the non-typical Yin-deficiency group (n = 61) and the non-Yin-deficiency group (n = 107). Their venous blood samples were collected in the morning while lying on their backs to detect plasma levels of adrenaline, noradrenaline, aldosterone, atrial natriuretic peptide (ANP), corticoid and myocardial enzymes, as well as their hospitalization days and mortality in hospitalized period were calculated and compared in the three groups, with the 30 healthy persons as control.

RESULTSLevels of serum creatine phosphokinase, creatine phosphokinase isozyme, plasma adrenaline, noradrenaline, aldosterone, hospitalization days and mortality were higher in the Yin-deficiency groups than in the non-Yin-deficiency group (P < 0.05, P < 0.01). As compared the indexes between the typical and the non-typical Yin-deficiency groups, significant difference only showed in plasma aldosterone and ANP, which was significantly higher in the former (P < 0.05, P < 0.01). Plasma corticoid level was insignificantly different between the Yin-deficieny groups.

CONCLUSIONPatients with AMI of Yin-deficiency type was severer in myocardial damage, with longer hospitalization period and higher mortality, it is probably due to the hyper-activated sympathetic-adrenaline system and strengthened activity of aldosterone in them.

Adult ; Aged ; Aged, 80 and over ; Creatine Kinase ; blood ; Diagnosis, Differential ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Myocardial Infarction ; diagnosis ; Prognosis ; Yin Deficiency ; diagnosis ; etiology