Dominant rhabdomyolysis linked to a recurrent ATP2A2 variant reducing SERCA2 function in muscle.

Rhabdomyolysis is an acute failure of cellular homeostasis resulting in muscle breakdown, triggered by trauma, infection, drugs or strenuous exercise. Recurrent rhabdomyolysis is often associated with genetic and metabolic defects of skeletal muscle. The sarcoendoplasmic reticulum Ca2+-ATPase 2 (SERCA2), encoded by the ATP2A2 gene, is an intracellular pump located in the sarcoplasmic and endoplasmic reticulum that is essential for maintaining intracellular calcium (Ca2+) homeostasis and is highly expressed in slow-twitch muscle.

The management and clinical outcomes of pregnancies in women with urea cycle disorders: A review of the literature and results of an international survey.

An increasing number of women with urea cycle disorders (UCDs) are reaching child-bearing age and becoming pregnant. Improved diagnostics and increased awareness of inherited metabolic diseases has also led to more previously undetected women being diagnosed with a UCD during or shortly after pregnancy. Pregnancy increases the risk of acute metabolic decompensation with hyperammonemia-which can occur in any trimester, and/or the postpartum period, and may lead to encephalopathy, psychosis, coma, and even death, if not diagnosed promptly and treated appropriately.

GPI-anchoring disorders and the heart: Is cardiomyopathy an overlooked feature?

Glycosylphosphatidylinositol anchoring disorders (GPI-ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA-encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy.

Genotype-phenotype correlation in contactin-associated protein-like 2 (CNTNAP-2) developmental disorder.

Contactin-associated protein-like 2 (CNTNAP2) gene encodes for CASPR2, a presynaptic type 1 transmembrane protein, involved in cell-cell adhesion and synaptic interactions. Biallelic CNTNAP2 loss has been associated with "Pitt-Hopkins-like syndrome-1" (MIM#610042), while the pathogenic role of heterozygous variants remains controversial. We report 22 novel patients harboring mono- (n = 2) and bi-allelic (n = 20) CNTNAP2 variants and carried out a literature review to characterize the genotype-phenotype correlation.

Abnormal concentrations of acetylated amino acids in cerebrospinal fluid in acetyl-CoA transporter deficiency.

Acetyl-CoA transporter 1 (AT-1) is a transmembrane protein which regulates influx of acetyl-CoA from the cytosol to the lumen of the endoplasmic reticulum and is therefore important for the posttranslational modification of numerous proteins. Pathological variants in the SLC33A1 gene coding for AT-1 have been linked to a disorder called Huppke-Brendel syndrome, which is characterized by congenital cataracts, hearing loss, severe developmental delay and early death. It has been described in eight patients so far, who all had the abovementioned symptoms together with low serum copper and ceruloplasmin concentrations.