ECEL1 related distal arthrogryposis 5D in an Indian cohort-Report of recognizable musculoskeletal phenotype and a possible founder variant.

Distal arthrogryposis type 5D (DA5D) is clinically characterized by knee extension contractures, distal joint contractures, clubfoot, micrognathia, ptosis, and scoliosis. We report nine affected individuals from eight unrelated Indian families with DA5D. Although the overall musculoskeletal phenotype is not very distinct from other distal arthrogryposis, the presence of fixed knee extension contractures with or without scoliosis could be an important early pointer to DA5D.

Clinical and Molecular Spectrum of Patients with Methylmalonic Acidemia.

Objectives: To study the clinical and molecular spectrum of Methylmalonic acidemia (MMA).

Methods: In this retrospective study, the records of 30 MMA patients were evaluated for their phenotype, biochemical abnormalities, genotype, and outcomes.

Results: Thirty patients with MMA (age range 0-21 y) from 27 unrelated families were enrolled.

Late-onset cobalamin C disease: rare but treatable.

Cobalamin C disease is the most common inborn error of cobalamin metabolism, resulting from mutations in methylmalonic aciduria and homocystinuria type C protein ) gene. There is associated elevation of homocysteine and methylmalonic acid and decreased synthesis of methionine. It is a multisystem disorder characterised by cognitive impairment, psychiatric manifestations, haematological manifestations and thromboembolic phenomena.

Diverse clinical manifestations and intrafamilial variability due to an inherited recurrent MYRF variant.

MYRF monoallelic variants have been described in syndromic forms characterized by cardiac-urogenital syndrome and isolated nanophthalmos with/without minor systemic manifestations. We describe a large family with a paternally inherited pathogenic variant in MYRF that manifested as congenital diaphragmatic hernia (CDH), cardiac and urogenital abnormalities, and/or nanophthalmos with significant intrafamilial variability.

A patient with POLA1 splice variant expands the yet evolving phenotype of Van Esch O'Driscoll syndrome.

Van Esch-O'Driscoll syndrome (VEODS) is a rare cause of syndromic X-linked intellectual disability characterised by short stature, microcephaly, variable degree of intellectual disability, and hypogonadotropic hypogonadism. To date, heterozygous hypomorphic variants in the gene encoding the DNA Polymerase α subunit, POLA1, have been observed in nine patients from five unrelated families with VEODS. We report a three-year-old child with VEODS having borderline intellectual disability due to a novel splice site variant causing exon 6 skipping and reduced POLA1 expression.

Hydrops fetalis in PKD1L1-related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum.

Abnormalities in the normal left-right axis asymmetry range from situs inversus totalis to situs ambiguous or heterotaxy. More than 80 genes have been described to have a role in the establishment of the normal situs of the internal organs. Pathogenic variants in the PKD1L1 gene have recently been described in heterotaxy and congenital heart disease.

The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective.

Quantitative estimates for the global impact of COVID-19 on the diagnosis and management of patients with inborn errors of metabolism (IEM) are lacking. We collected relevant data from 16 specialized medical centers treating IEM patients in Europe, Asia and Africa. The median decline of reported IEM related services in March 1st-May 31st 2020 compared to the same period in 2019 were as high as 60-80% with a profound impact on patient management and care for this vulnerable patient group.

Right Internal Jugular Vein Phlebectasia: A Rare Cause of Neck Swelling.

Internal jugular vein (IJV) phlebectasia is a rare condition presenting as a self-reducible soft tissue swelling of the neck due to fusiform dilation of the venous wall. We report the case of a 7-year-old boy who presented with painless soft mass in the side of the neck which appears during coughing and straining and reduces spontaneously. Diagnosis was confirmed by Doppler ultrasonography and magnetic resonance imaging of the neck.