Glutathione synthetase deficiency (GSSD) is an autosomal-recessive metabolic disorder caused by glutathione synthetase (GSS) gene mutations. No more than 90 cases of GSSD have been reported worldwide; thus, the spectrum of GSS mutations and the genotype-phenotype association remain unclear. Here, we present a severely affected infant carrying a compound heterozygous GSS variation, c.491G > A, and a novel variant of c.1343_1348delTACTTC. We also summarize the clinical manifestations, treatment protocol, prognosis, and genetic characteristics of previously reported GSSD cases in China. In this case study, our patient presented with tachypnea, jaundice, intractable metabolic acidosis, and hemolytic anemia. Urinary-organic acid analysis revealed elevated 5-oxoproline levels. Further, this patient showed improved outcomes owing to early diagnosis and the timely administration of vitamins C and E. Therefore, our study indicates that in clinical cases of unexplained hemolytic anemia and metabolic acidosis, GSSD should be considered. Additionally, genetic testing and antioxidant application might help identify GSSD and improve the prognosis.

UNASSIGNED: Isovaleric acidaemia (IVA), characterized by an acute metabolic crisis and psychomotor delay, is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD).
UNASSIGNED: We report the case of a Chinese patient with IVA who was admitted to Tianjin Children\'s Hospital and followed up for 8 years. Genetic analysis of the patient and his parents was conducted using the whole-exome sequencing and Sanger sequencing. We searched for similar reported cases in the PubMed and Wanfang databases using the term \"isovaleric acidaemia,\" reviewed the related literature to obtain a summary of the clinical and genetic characteristics, and analyzed the genotype-phenotype correlations.
UNASSIGNED: The patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. We identified compound heterozygous variants of the IVD gene, including the unreported variant c.224A>G (p.Asn75Ser) and the reported variant c.1195G>C (p.Asp399His). The child was prescribed a low-protein diet supplemented with L-carnitine. During the 8-year follow-up, no metabolic disorder or encephalopathic symptoms recurred. At present, the child is 11 years of age and has normal mental and motor performance. Another 154 cases identified in 25 relevant references were combined with this case, resulting in a sample of 155 patients, including 52 asymptomatic patients, 64 with neonatal onset, and 39 with the chronic intermittent disease with onset from ages of 1 month to 10 years (median age, 2 years). Among articles that reported sex, the male-to-female ratio was 1:1.06. The cardinal symptoms included vomiting, lethargy, \"sweaty foot\" odor, poor feeding, developmental delay, and epilepsy. The proportion of variants in regions 123-159 and 356-403 of the IVD protein was greater in symptomatic patients than in asymptomatic patients. Conversely, in asymptomatic patients, the proportion of variants in the 282-318 region was greater than in symptomatic patients.
UNASSIGNED: This case report describes an unreported variant c.224A>G (p.Asn75Ser) of the IVD gene, and summarizes previously reported cases. Furthermore, the correlation between the genotype and clinical phenotype of IVA is analyzed to improve the understanding of this disease.

Nonketotic hyperglycinemia (NKH) is a lethal autosomal recessive disease resulting from alterations in glycine metabolism, commonly caused by mutations in glycine decarboxylase (GLDC). The symptoms of NKH usually manifest in the neonatal period, and can be categorized into severe NKH and attenuated NKH based on the clinical outcome. To date, only a few NKH cases have been reported in China. We here report a case of a neonate with severe NKH carrying a novel compound heterozygous variant in GLDC. The patient was a 68-h-old girl who had progressive lethargy, no crying, and poor sucking ability from birth, and was therefore transferred to our department. On admission, the patient was supported by intubation and ventilation and presented with profound coma. Metabolic investigation indicated a markedly increased glycine concentration both in the plasma and cerebrospinal fluid (CSF). Symptomatic treatments were administered, but the patient\'s condition did not improve substantially. Whole-exome sequencing identified compound heterozygous mutations (c.1261G>C, p.G421R and c.450 C>G, p.N150K) in GLDC, which were inherited from the mother and the father, respectively. The patient was hospitalized for 8 days in our department and died 2 days after discharge. We further summarize the clinical features, genetic characteristics, administered treatment, and prognosis of previously reported Chinese NKH patients for context. Our results highlight that due to the non-specific clinical phenotypes of NKH and difficulty in obtaining CSF samples, genetic testing is a crucial tool, not only for a diagnosis but also for predicting the clinical outcome and can potentially help to determine the optimal therapeutic strategy.

Maple Syrup Urine Disease (MSUD) is a rare inherited disorder of branched chain amino acid metabolism characterized by cerebral edema and death in uncorrected metabolic crisis. It is conventionally treated with intensive nutritional therapy to prevent and correct metabolic crisis. This paper reports the use of growth hormone as a pharmacologic rescue agent in the case of an 11-year-old male with MSUD and metabolic crisis refractory to standard interventions. The initiation of short courses of growth hormone correlated with corrected mental status, resolution of metabolic acidosis, and improvement in plasma leucine levels on two occasions during an admission to the pediatric intensive care unit. This is the first known case report of the use of growth hormone in MSUD since contemporary dietary management became available. The discussion includes a literature review of the use of growth hormone in inherited diseases of amino acid metabolism and a brief discussion of protein anabolic pharmacotherapeutic agents shown to improve net protein balance in pediatric burn patients. We propose that growth hormone and other protein anabolic agents may be valuable adjuvants to standard therapy in children with inherited metabolic disease.

PYGL mutations can cause liver phosphorylase deficiency, resulting in a glycogenolysis disorder, namely, glycogen storage disease (GSD) VI. The disease is rarely reported in the Chinese population. GSD VI is mainly characterized in untreated children by hepatomegaly, growth retardation and elevated liver transaminases.
In this study, we report two GSD VI patients with growth retardation and abnormal liver function. There was no obvious hepatomegaly for one of them. Whole exome sequencing (WES) combined with copy number variation analysis was performed. We found a novel homozygous gross deletion, c.1621-258_2178-23del, including exons 14-17 of PYGL in patient 1. The exons 14-17 deletion of PYGL resulted in an in-frame deletion of 186 amino acids. Compound heterozygous mutations of PYGL were identified in patient 2, including a novel missense mutation c.1832C > T/p.A611V and a recurrent nonsense mutation c.280C > T/p.R94X. After treatment with uncooked cornstarch (UCS) 8 months for patient 1 and 13 months for patient 2, the liver transaminases of both patients decreased to a normal range and their stature was improved. However, patient 1 still showed mild hypertriglyceridemia.
We describe two GSD VI patients and expand the spectrum of PYGL mutations. Patient 1 in this study is the first GSD VI case that showed increased transaminases without obvious hepatomegaly due to a novel homozygous gross deletion of PYGL identified through WES.