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EClinicalMedicine 2022 Jul 27;49:101466. Epub 2022 May 27.

Department of Cardiology, Shanghai Children's Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Background: Few data on paediatric hypertrophic cardiomyopathy (HCM) are available in developing countries. A multicentre, retrospective, cohort study was conducted to profile the clinical characteristics and survival of children with HCM in China.

Methods: We collected longitudinal data on children with HCM aged 0-18 years at three participating institutions between January 1, 2010 and December 31, 2019. Read More

J Pers Med 2022 Jun 1;12(6). Epub 2022 Jun 1.

Department of Paediatrics, Faculty of Medicine Comenius University in Bratislava and National Institute of Children's Diseases in Bratislava, 83340 Bratislava, Slovakia.

Fabry disease (FD, OMIM#301500) is a rare inborn error of the lysosomal enzyme α-galactosidase (α-Gal A, EC 3.2.1. Read More

Cold Spring Harb Mol Case Stud 2022 Jun 22;8(4). Epub 2022 Jun 22.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York 10032, USA.

Vacuolar ATPases (V-ATPases) are large multisubunit proton pumps conserved among all eukaryotic cells that are involved in diverse functions including acidification of membrane-bound intracellular compartments. The gene encodes an accessory subunit of the vacuolar (V)-ATPase protein pump. Pathogenic variants in have been described in association with a congenital disorder of glycosylation (CDG), which are highly variable, but often characterized by immunodeficiency, hepatopathy, and neurologic manifestations. Read More

BMJ Case Rep 2022 Jun 22;15(6). Epub 2022 Jun 22.

Pediatrics, Umm Al-Qura University College of Medicine, Makkah, Saudi Arabia

Barth syndrome (BTHS) is an X linked recessive disorder caused by a mutation in the tafazzin (TAZ) gene classically associated with the triad of neutropaenia and cardiac and skeletal myopathies. Here we present a case of BTHS in a 2-month-old male patient found to have a novel variant of the TAZ gene (hemizygous c.639G>A) leading to early termination of the tafazzin protein (p. Read More

J Int Med Res 2022 Jun;50(6):3000605221106412

Department of Pediatrics, Chattogram Medical College Hospital, Panchlaish, Chattogram, Bangladesh.

In resource-constrained settings, mucopolysaccharidosis (MPS) is a rare hereditary metabolic illness that frequently remains undiagnosed. We present a scenario that illustrates the challenges in diagnosing and managing MPS because of test inaccessibility, and we propose potential approaches to minimize the hurdles. We recommend that physicians anticipate a rare genetic disease, such as MPS, based on the clinical history findings from routine radiological investigations. Read More

Orphanet J Rare Dis 2022 06 20;17(1):241. Epub 2022 Jun 20.

Division of Metabolism, Department of Pediatric Subspecialties, Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Background: Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and hepatomegaly are hallmarks of disease, but muscular and renal tubular involvement, dyslipidemia and osteopenia can develop. Considering the paucity of literature available, herein we provide a narrative review of these latter forms of GSDs. Read More

J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096221105245

Children's Hospital Los Angeles, CA, USA.

We report a case of a fetus with a prenatal diagnosis of classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Although CAH is typically assessed postnatally, this fetal case had multiple prenatal clinical assessments made feasible by an interdisciplinary CAH center. The approach facilitated the development and delivery of comprehensive and earlier care for the fetus, and the family living with this complex, congenital condition, with perinatology, endocrinology, genetic counseling, psychology, and urology involvement. Read More

J Inherit Metab Dis 2022 Jun 20. Epub 2022 Jun 20.

University Medical Center St Radboud Nijmegen, Nijmegen, The Netherlands.

Introduction: Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine-tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral and social outcomes of treated TT1 and PKU patients. Read More

Semin Nephrol 2022 Mar;42(2):114-121

Division of Pediatric Nephrology, Department of Pediatrics, University of Minnesota Masonic Children's Hospital, Minneapolis, MN. Electronic address:

A number of genes that cause inherited kidney disorders reside on the X chromosome. Given that males have only a single active X chromosome, these disorders clinically manifest primarily in men and boys. However, phenotypes in female carriers of X-linked kidney conditions are becoming more and more recognized. Read More

Indian J Pediatr 2022 Jun 17. Epub 2022 Jun 17.

Pediatric Biochemistry Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Objectives: To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques.

Methods: Children considered high-risk for IEM were screened for metabolic diseases during a 3-y period. Dried blood spots and urine samples were analyzed by tandem mass spectrometry (LC-MS/MS) and gas chromatograph-mass spectrometry (GCMS). Read More

Front Genet 2022 26;13:859837. Epub 2022 May 26.

Newborn Screening Translational Research Network, American College of Medical Genetics and Genomics, Bethesda, MD, United States.

With the rapid increase in publicly available sequencing data, healthcare professionals are tasked with understanding how genetic variation informs diagnosis and affects patient health outcomes. Understanding the impact of a genetic variant in disease could be used to predict susceptibility/protection and to help build a personalized medicine profile. In the United States, over 3. Read More

Front Endocrinol (Lausanne) 2022 24;13:882863. Epub 2022 May 24.

Department of Endocrinology, Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China.

Objective: 11β-Hydroxylase deficiency (11β-OHD) caused by mutations in the gene is the second most common form of congenital adrenal hyperplasia. Both point mutations and genomic rearrangements of are important causes of 11β-OHD. However, the high degree of sequence identity between and its homologous gene , presents unique challenges for molecular diagnosis of suspected 11β-OHD. Read More

Int J Environ Res Public Health 2022 Jun 2;19(11). Epub 2022 Jun 2.

CDG & Allies-Professionals and Patient Associations International Network (CDG & Allies-PPAIN), Department of Life Sciences, School of Science and Technology, NOVA University Lisbon, 2819-516 Caparica, Portugal.

Congenital Disorders of Glycosylation (CDG) are a large family of rare genetic diseases for which effective therapies are almost nonexistent. To better understand the reasons behind this, to analyze ongoing therapy research and development (R&D) for CDG, and to provide future guidance, a community-led mixed methods approach was organized during the 4th World Conference on CDG for Families and Professionals. In the quantitative phase, electronic surveys pointed to the prioritization of six therapeutic R&D tools, namely biobanks, registries, biomarkers, disease models, natural history studies, and clinical trials. Read More

Cells 2022 Jun 4;11(11). Epub 2022 Jun 4.

Molecular Medicine-IRCCS Stella Maris, 56128 Pisa, Italy.

CLN5 disease (MIM: 256731) represents a rare late-infantile form of neuronal ceroid lipofuscinosis (NCL), caused by mutations in the gene that encodes the CLN5 protein (CLN5p), whose physiological roles stay unanswered. No cure is currently available for CLN5 patients and the opportunities for therapies are lagging. The role of lysosomes in the neuro-pathophysiology of CLN5 disease represents an important topic since lysosomal proteins are directly involved in the primary mechanisms of neuronal injury occurring in various NCL forms. Read More

Cells 2022 Jun 4;11(11). Epub 2022 Jun 4.

Department of Pediatric Nephrology and Development and Regeneration, University Hospitals Leuven, University of Leuven, 3000 Leuven, Belgium.

Early diagnosis and effective therapy are essential for improving the overall prognosis and quality of life of patients with nephropathic cystinosis. The severity of kidney dysfunction and the multi-organ involvement as a consequence of the increased intracellular concentration of cystine highlight the necessity of accurate monitoring of intracellular cystine to guarantee effective treatment of the disease. Cystine depletion is the only available treatment, which should begin immediately after diagnosis, and not discontinued, to significantly slow progression of renal and extra-renal organ damage. Read More

PLoS One 2022 9;17(6):e0269561. Epub 2022 Jun 9.

Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background And Aims: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate. Read More

Mol Genet Metab Rep 2022 Sep 3;32:100884. Epub 2022 Jun 3.

University of Pittsburgh School of Medicine, USA.

Purpose: Mitochondrial trifunctional protein deficiency (TFPD) and isolated long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) are two related defects of fatty acid β -oxidation. While NBS has decreased mortality, morbidity remains significant. Additionally, the relationship of genotype to clinical outcome remains unclear. Read More

Nat Commun 2022 Jun 7;13(1):3278. Epub 2022 Jun 7.

Necker Hospital, APHP, Reference Center for Inborn Error of Metabolism, Pediatrics Department, Paris Cité University, Filière G2M, Paris, France.

Maple syrup urine disease (MSUD) is a rare recessively inherited metabolic disorder causing accumulation of branched chain amino acids leading to neonatal death, if untreated. Treatment for MSUD represents an unmet need because the current treatment with life-long low-protein diet is challenging to maintain, and despite treatment the risk of acute decompensations and neuropsychiatric symptoms remains. Here, based on significant liver contribution to the catabolism of the branched chain amino acid leucine, we develop a liver-directed adeno-associated virus (AAV8) gene therapy for MSUD. Read More

BMJ Case Rep 2022 Jun 7;15(6). Epub 2022 Jun 7.

Pediatrics, KS Hegde Medical Academy, Mangalore, Karnataka, India.

Inborn errors of metabolism constitute a differential diagnosis in infants presenting with encephalopathy in developing countries where expanded newborn screening is not a state health programme. Acute neurological presentation with encephalopathy is documented in paediatric COVID-19. The pandemic has also altered parents' healthcare-seeking behaviour, leading to delays in emergency care. Read More

Front Endocrinol (Lausanne) 2022 18;13:862022. Epub 2022 May 18.

Radiology Division, King Abdulaziz Specialist Hospital, Taif, Saudi Arabia.

Background: Vitamin D-dependent rickets type 1A (VDDR1A) rickets is an uncommon kind of rickets that affects both boys and girls. Children with mutations are normal at birth and present at around 6 months to 2 years of age with symptoms. When suspected, genetic testing is required to confirm the diagnosis. Read More

Neuroradiology 2022 Jun 4. Epub 2022 Jun 4.

Inborn Errors of Metabolism Unit, Pediatric Neurology Department, Institut de Recerca Sant Joan de Déu, and MetabERN, Hospital Sant Joan de Déu, Passeig Sant Joan De Deu Nº 2, 08950, Esplugues De Llobregat, Barcelona, Spain.

Purpose: Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. Read More

Mol Genet Metab 2022 Jul 25;136(3):199-218. Epub 2022 May 25.

Department of Clinical Genetics, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands. Electronic address:

The integration of metabolomics data with sequencing data is a key step towards improving the diagnostic process for finding the disease-causing genetic variant(s) in patients suspected of having an inborn error of metabolism (IEM). The measured metabolite levels could provide additional phenotypical evidence to elucidate the degree of pathogenicity for variants found in genes associated with metabolic processes. We present a computational approach, called Reafect, that calculates for each reaction in a metabolic pathway a score indicating whether that reaction is deficient or not. Read More

Zhonghua Er Ke Za Zhi 2022 Jun;60(6):604-607

Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Zhonghua Er Ke Za Zhi 2022 Jun;60(6):533-538

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored. The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children's Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively. There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. Read More

Zhonghua Er Ke Za Zhi 2022 Jun;60(6):501-506

J Child Neurol 2022 Jun 3:8830738221106896. Epub 2022 Jun 3.

Division of Neurogenetics and Developmental Pediatrics, 8404Children's National Hospital, Washington DC, USA.

The practice of child neurology has changed significantly in the past two decades as we have integrated genetic testing into our standard of care to achieve precise diagnoses and to guide management of many childhood neurological conditions. Despite this paradigm shift, there appears to be a gap in both clinical exposure to neurogenetic disorders and education provided to residents in ordering and interpreting genetic testing. We therefore conducted a national survey for child neurology trainees in all programs across the United States to delineate their perception of the adequacy of current training and didactics in genetic/neurogenetic disorders. Read More

J Musculoskelet Neuronal Interact 2022 06;22(2):284-291

University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Pediatrics, Cologne, Germany.

The results of three cases with infantile-onset Pompe disease participating in a rehabilitation program with home-based vibration training will be presented. In this retrospective observational case study, the cases participated in the neuromuscular training program "Auf die Beine", which combines two blocks of intensive, goal directed training with 6 months of home-based whole body vibration (WBV). Assessments by the means of a dual-energy X-ray absorptiometry and grip strength were applied at multiple points throughout the program. Read More

Sci Rep 2022 May 31;12(1):9084. Epub 2022 May 31.

Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.

Purine nucleoside phosphorylase (PNP) is an important enzyme in the purine degradation and salvage pathway. PNP deficiency results in marked T lineage lymphopenia and severe immunodeficiency. Additionally, PNP-deficient patients and mice suffer from diverse non-infectious neurological abnormalities of unknown etiology. Read More

Sci Rep 2022 May 30;12(1):9025. Epub 2022 May 30.

Pediatrics and Rare Diseases Group, Sanford Research, 2301 E. 60th Street N., South Dakota, Sioux Falls, 57104, USA.

We recently demonstrated that HCl-acidified drinking water, which is widely used in laboratory animal facilities, had some beneficial effects in the Cln3 mouse model of juvenile Batten disease, a neurodegenerative lysosomal storage disorder. Here we tested if acidified drinking water has therapeutic effects in Cln1 nonsense mutant mice, a model of the infantile form of Batten disease. In Cln1 mice, acidified drinking water received from weaning prevented the impairment in pole climbing ability measured at 3 and 6 months of age. Read More

Elife 2022 05 30;11. Epub 2022 May 30.

Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.

DNA Methyltransferase 3 A (DNMT3A) is an important facilitator of differentiation of both embryonic and hematopoietic stem cells. Heterozygous germline mutations in lead to Tatton-Brown-Rahman Syndrome (TBRS), characterized by obesity and excessive height. While DNMT3A is known to impact feeding behavior via the hypothalamus, here we investigated a role in adipocyte progenitors utilizing heterozygous knockout mice that recapitulate cardinal TBRS phenotypes. Read More