Evaluation of 73 Enlisted Patients for Liver Transplant with Unknown Etiology Reveals a Late-Diagnosed Case of Lysosomal Acid Lipase Deficiency.

Lysosomal acid lipase deficiency (LALD) varies from a severe infantile-onset form (Wolman disease) to a late-onset form known as cholesteryl ester storage disease (CESD), both of which are autosomal recessive disorders caused by biallelic pathogenic variants. We evaluated seventy-three patients enlisted for liver transplant (LT) at Instituto da Criança (HCFMUSP-Brazil) who were subjected to LAL activity measurement and Sanger sequencing analysis, resulting in a positive LALD diagnosis for only one of these individuals. This LALD patient presented recurrent diarrhea, failure to thrive, hepatomegaly, and dyslipidemia at the age of 4 months and liver failure by the age of 13 years.

Subacute Partially Reversible Leukoencephalopathy Expands the Aicardi-Goutières Syndrome Phenotype.

Objective: To report a series of atypical presentations of Aicardi-Goutières syndrome.

Methods: Clinical, neuroimaging, and genetic data.

Results: We report a series of six unrelated patients (five males) with a subacute loss of developmental milestones, pyramidal signs, and regression of communication abilities, with onset at ages ranging from 7 to 20 months, reaching a nadir after 4 to 24 weeks.

MECP2-related conditions in males: A systematic literature review and 8 additional cases.

Objective: To present a cohort of 8 males and perform a systematic review of all published cases with a single copy of MECP2 carrying a pathogenic variant.

Methods: We reviewed medical records of males with a single copy of MECP2 carrying a pathogenic variant. We searched in Medline (Pubmed) and Embase to collect all articles which included well-characterized males with a single copy of MECP2 carrying a pathogenic or likely pathogenic variant in MECP2 (1999-2020).

Application of Whole-Exome Sequencing in Detecting Copy Number Variants in Patients with Developmental Delay and/or Multiple Congenital Malformations.

Overcoming challenges for the unambiguous detection of copy number variations is essential to broaden our understanding of the role of genomic variants in the clinical phenotype. With the improvement of software and databases, whole-exome sequencing quickly can become an excellent strategy in the routine diagnosis of patients with a developmental delay and/or multiple congenital malformations. However, even after a detailed analysis of pathogenic single-nucleotide variants and indels in known disease genes, using whole-exome sequencing, some patients with suspected syndromic conditions are left without a conclusive diagnosis.

Heterozygous loss of function of is associated with intellectual deficiency, rolandic epilepsy, and language impairment.

Recognition of a de novo mutation in associated with a neurodevelopmental phenotype reinforces its role in 2q23q24 microdeletion syndrome. Using the proband WES data and the probability of loss-of-function intolerance index (pLi) set at 1.0 (highest intolerance constraint), we could target as the candidate gene in this patient.

Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations.

The Na/K- ATPase acts as an ion pump maintaining the essential plasma membrane potential in all mammalian cell types, and is essential for many cellular functions. There are four α isoforms (α1, α2, α3 and α4) with distinct expression patterns, kinetic properties and substrate affinity. The α2-isoform is encoded by ATP1A2 and evidence supports its utmost importance in Cl homeostasis in neurons, and in the function of respiratory neurons at birth.

The immediate effects of local and adjacent acupuncture on the tibialis anterior muscle: a human study.

Background: This study compares the immediate effects of local and adjacent acupuncture on the tibialis anterior muscle and the amount of force generated or strength in Kilogram Force (KGF) evaluated by a surface electromyography.

Methods: The study consisted of a single blinded trial of 30 subjects assigned to two groups: local acupoint (ST36) and adjacent acupoint (SP9). Bipolar surface electrodes were placed on the tibialis anterior muscle, while a force transducer was attached to the foot of the subject and to the floor.