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Serum cholinesterase (ChE) level is important for the diagnosis and prognostic evaluation of various diseases such as liver diseases and toxic diseases, and butyrylcholinesterase (BuChE) is an important component of ChE. Mutations in the BCHE gene can cause a significant reduction in the level of BuChE, with extensive reports in European and American populations and relatively few reports in Eastern countries, particularly China. This study describes a male patient, aged 35 years, who was misdiagnosed with organophosphorus pesticide poisoning due to an extreme reduction in ChE level and was given detoxification therapy, but such diagnosis was excluded by various biochemical examinations. Finally whole-exome sequencing and Sanger sequencing revealed the complex heterozygous mutations of c.1027dup and c.401dup at exon 2 of the BCHE gene, and hereditary BuChE deficiency due to these mutations is the cause of the extreme reduction in ChE level. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the disease spectrum, incidence rate and gene variation spectrum of neonatal inherited metabolic diseases in Gansu province, and to explore the genetic characteristics of these diseases. Methods: 213 786 cases with the dried blood spots were screened by tandem mass spectrometry from January 2021 to December 2023. The suspected positive children were diagnosed by urine gas chromatography mass spectrometry or (and) high-throughput gene sequencing. The spectrum of disease, incidence and gene variation were analyzed. Results: 145 cases were diagnosed in 189 high risk newborns, including 15 kinds of inherited metabolic diseases. The total incidence of inherited metabolic diseases in Gansu was 1/1 474, among which 68.28% (99 cases) were hyperphenylalanine. A total of 268 mutation sites related to 20 mutation genes were found, such as some hot spot mutations: c.728G>A, c.611A>G mutations in PAH gene, c.609G>A, c.567dupT mutations in MMACHC gene, and the new variants not reported: c.298G>T mutation in MMACHC gene, c.2000A>G mutation in MUT gene, c.734-7A>G mutation in MMAA gene. Conclusions: Mass spectrometry combined with gene detection can effectively explore the genetic characteristics of inherited metabolic diseases, which provides data support for follow-up clinical diagnosis and genetic counseling of these diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Neuronal ceroid lipofuscinosis (NCL) is a heterogeneous group of 13 rare, progressive neurodegenerative diseases of the brain and retina. CLN14 is a very rare subtype of NCL caused by pathogenic variants in the KCTD7 gene. Only four cases of this subtype have been reported in the literature. Case presentation A nine-month-old, previously healthy male who was firstborn to first-cousin parents presented with progressive psychomotor regression, dysmorphic facial features, myoclonus, and vision loss. Neurological examination showed generalized hypotonia and brisk reflexes. He continued to deteriorate until age 18 months, when he developed his first generalized tonic-clonic seizure. An ophthalmological examination showed a hypopigmented fundus and slight temporal disc pallor. Brain MRI showed mild generalized brain atrophy and white matter disease. EEG revealed a severely abnormal trace marked by generalized, high amplitude, sharply contoured, polymorphic delta slowing intermixed with theta slowing and some alpha activity, with disorganized and scattered spikes and sharp waves. The patient continued to have uncontrolled seizures and further psychomotor regression until he died of status epilepticus and pneumonia at the age of 44 months. WES identified a novel homozygous variant c.413T > C, p.(Leu138Pro) in the KCTD7 gene, causing an amino acid transition from leucine to proline at position 138. Both parents were carriers of the same variant. Conclusions We present the fifth known case of CLN14 in the literature and report the clinical course and a novel underlying likely causative variant in the KCTD7 gene. The improving accessibility and affordability of genetic testing will likely uncover more NCL cases and further expand the disease’s genotypic and phenotypic spectrum.

Maternally inherited diabetes and deafness (MIDD) is a rare mitochondrial disorder primarily resulting from m.3243A>G mutation. The clinical characteristics of MIDD exhibit significant heterogeneity. Our study aims to delineate these characteristics and determine the potential correlation with m.3243A>G heteroplasmy levels. This retrospective, descriptive study encompassed patients with confirmed m.3243A>G mutation and diabetes mellitus at Seoul National University Hospital. Our cohort comprises 40 patients with MIDD, with a mean age at study enrollment of 33.3±12.9 years and an average % of heteroplasmy of 30.0%±14.6% in the peripheral blood. The most prevalent comorbidity was hearing loss (90%), followed by albuminuria (61%), seizure (38%), and stroke (33%). We observed a significant negative correlation between % of heteroplasmy and age at diabetes diagnosis. These clinical features can aid in the suspicion of MIDD and further consideration of genetic testing for m.3243A>G mutation.