Mechanographic analysis of the timed 4 stair climb test - methodology and reference data of healthy children and adolescents.

Objectives: The timed 4 stair climb test (4SC) is an accepted and widely used tool to assess motor function of patients with neuromuscular diseases. We aimed to establish reference data for the 4SC, and for mechanographic analysis of ascent (4SC-Up) and descent (4SC-Dn) in healthy children and adolescents.

Methods: We used a custom-made staircase measuring device to assess force, power and velocity during the ascent of 4 stairs in healthy subjects.

Cathepsin D as biomarker in cerebrospinal fluid of nusinersen-treated patients with spinal muscular atrophy.

Background And Purpose: The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the past 4 years, but treatment responses differ remarkably between individuals, and therapeutic decision-making remains challenging, underlining the persistent need for validated biomarkers.

Methods: We applied untargeted proteomic analyses to determine biomarkers in cerebrospinal fluid (CSF) samples of SMA patients under treatment with nusinersen. Identified candidate proteins were validated in CSF samples of SMA patients by Western blot and enzyme-linked immunosorbent assay.

MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase.

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms.

Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder.

GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and cerebellar ataxia harboring biallelic variants in the GEMIN5 gene. Mutations in GEMIN5 perturb the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners in patient iPSC-derived neurons, suggesting a potential loss-of-function mechanism.

Post-dural puncture headache-a single-centre analysis in paediatric patients with and without SMA.

Aim: To gather epidemiologic data on post-dural puncture headache (PDPH) after diagnostic or therapeutic lumbar puncture (LP) in children and adolescents with SMA as well as in a cohort of paediatric patients without SMA.

Methods: We performed a retrospective, single-centre analysis via chart review and questionnaire. Patients were identified using the German procedure classification.