Role of continuous glucose monitoring in the management of glycogen storage disorders
This study revealed that in addition to overnight hypoglycemia, CGMS can uncover previously undetected, subclinical, low glucose levels during daytime hours. Additionally, the CGMS detected daytime and overnight hyperglycemia, an often overlooked concern in liver GSDs. The CGMS with concurrent dietary adjustments made by a metabolic dietitian improved metabolic parameters and stabilized blood glucose levels. The CGMS was found to be a safe, effective, an d reliable method for optimizing treatment in patients with GSD I, III, and IX. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 25, 2018 Category: Internal Medicine Source Type: research

Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia
ConclusionrAAV-GPE-hG6PC treatment in GSD-Ia dogs was found to be safe and efficacious. GSD-Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD-Ia can also serve as a model for other hepatic monogenic disorders. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 25, 2018 Category: Internal Medicine Source Type: research

Inborn errors of coenzyme A metabolism and neurodegeneration
AbstractTwo inborn errors of coenzyme A (CoA) metabolism are responsible for distinct forms of neurodegeneration with brain iron accumulation (NBIA), a heterogeneous group of neurodegenerative diseases having as a common denominator iron accumulation mainly in the inner portion of globus pallidus. Pantothenate kinase-associated neurodegeneration (PKAN), an autosomal recessive disorder with progressive impairment of movement, vision and cognition, is the most common form of NBIA and is caused by mutations in the pantothenate kinase 2 gene (PANK2), coding for a mitochondrial enzyme, which phosphorylates vitamin B5 in the fir...
Source: Journal of Inherited Metabolic Disease - May 16, 2018 Category: Internal Medicine Source Type: research

The cholic acid extension study in Zellweger spectrum disorders: results and implications for therapy
ConclusionsAlthough CA treatment did lead to reduced levels of toxic C27-bile acid intermediates in ZSD patients without severe liver fibrosis or cirrhosis, no improvement of clinically relevant parameters was observed after 21  months of treatment. We discuss the implications for CA therapy in ZSD based on these results. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 15, 2018 Category: Internal Medicine Source Type: research

Evaluation of plasma biomarkers of inflammation in patients with maple syrup urine disease
In conclusion, our findings in plasma of patients with MSUD suggest that inflammation may play an important role in the pathogenesis of MSUD, although this process is not directly associated with BCAA blood levels. Ov erall, data reported here are consistent with the working hypothesis that inflammation may be involved in the pathophysiological mechanism underlying the brain damage observed in MSUD patients. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 8, 2018 Category: Internal Medicine Source Type: research

Sirtuin signaling controls mitochondrial function in glycogen storage disease type Ia
AbstractGlycogen storage disease type Ia (GSD-Ia) deficient in glucose-6-phosphatase- α (G6Pase-α) is a metabolic disorder characterized by impaired glucose homeostasis and a long-term complication of hepatocellular adenoma/carcinoma (HCA/HCC). Mitochondrial dysfunction has been implicated in GSD-Ia but the underlying mechanism and its contribution to HCA/HCC development remain unc lear. We have shown that hepatic G6Pase-α deficiency leads to downregulation of sirtuin 1 (SIRT1) signaling that underlies defective hepatic autophagy in GSD-Ia. SIRT1 is a NAD+-dependent deacetylase that can deacetylate and ac...
Source: Journal of Inherited Metabolic Disease - May 8, 2018 Category: Internal Medicine Source Type: research

Acknowledgement to Referees
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 7, 2018 Category: Internal Medicine Source Type: research

In memoriam
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 7, 2018 Category: Internal Medicine Source Type: research

Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis
AbstractIntroductionLong-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM).MethodsPatient data (n = 33; 14 adults, 19 paediatric) from the clinical development programme for velmanase alfa were integrated in this prospectively-designed analysis of long-term efficacy and safety. Patients who participated in the phase I/II or phase III trials and were continuing to receive treatment after com pletion of the trials were invited to participate in a comprehensive evaluation v...
Source: Journal of Inherited Metabolic Disease - May 3, 2018 Category: Internal Medicine Source Type: research

Patterns, evolution, and severity of striatal injury in insidious- versus acute-onset glutaric aciduria type 1
ConclusionsInsidious-onset type GA1 is characterized by dorsolateral putaminal lesions, less severe dystonia, and an asymptomatic latency phase, despite already existing lesions. Initially normal MRI during the first months and deviations from guideline-recommended treatment in a large proportion of insidious-onset patients substantiate the protective effect of neonatally initiated treatment. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 2, 2018 Category: Internal Medicine Source Type: research

Clinical, biochemical, and molecular overview of transaldolase deficiency and evaluation of the endocrine function: update of 34 patients
AbstractBackgroundTransaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype –genotype correlation.MethodsWe performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations o...
Source: Journal of Inherited Metabolic Disease - May 2, 2018 Category: Internal Medicine Source Type: research

Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review
AbstractMany inborn errors of metabolism (IEMs) are amenable to treatment; therefore, early diagnosis and treatment is imperative. Despite recent advances, the genetic basis of many metabolic phenotypes remains unknown. For discovery purposes, whole exome sequencing (WES) variant prioritization coupled with clinical and bioinformatics expertise is the primary method used to identify novel disease-causing variants; however, causation is often difficult to establish due to the number of plausible variants. Integrated analysis of untargeted metabolomics (UM) and WES or whole genome sequencing (WGS) data is a promising systema...
Source: Journal of Inherited Metabolic Disease - May 2, 2018 Category: Internal Medicine Source Type: research

Severe ichthyosis in MPDU1-CDG
We report on an infant with severe ichthyosis caused by MPDU1 mutations. The case illustrates that skin manifestations are an important feature of CDG syndromes. Therefore, metabolic investigations should be included in the workup of infantile ichthyosis disorders. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 2, 2018 Category: Internal Medicine Source Type: research

Presentation, progression, and predictors of ovarian insufficiency in classic galactosemia
AbstractClassic galactosemia (CG) is an inherited metabolic disorder that affects about 1 in 50,000 live births in the United States and many other countries. With the benefit of early detection by newborn screening and rapid dietary restriction of galactose, generally achieved by removing dairy from the diet, most affected infants are spared the acute and potentially lethal symptoms of disease. Despite early detection and life-long dietary intervention, however, most patients grow to experience a constellation of long-term complications that include premature ovarian insufficiency in the vast majority of girls and young w...
Source: Journal of Inherited Metabolic Disease - May 2, 2018 Category: Internal Medicine Source Type: research

Mucolipidosis type III, a series of adult patients
ConclusionsSevere skeletal abnormalities, resulting from abnormal bone development and severe progressive osteoarthritis, are the hallmark of MLIII, necessitating surgical orthopaedic interventions early in life. Future therapies for this disease should focus on improving cartilage and bone quality, preventing skeletal complications and improving mobility. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - April 27, 2018 Category: Internal Medicine Source Type: research

Medical and financial burden of acute intermittent porphyria
AbstractIntroductionA small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers.MethodsData from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. We collected symptoms related to porphyria, porphyria related complications...
Source: Journal of Inherited Metabolic Disease - April 19, 2018 Category: Internal Medicine Source Type: research

Intrafamilial oocyte donation in classic galactosemia: ethical and societal aspects
This study aimed to provide guidance in aspects to con sider based on the views of different groups involved in the oocyte donation process. A qualitative study using in-depth semi-structured interviews with>  50 participants (patients, family members, and healthcare providers) was conducted. From these interviews, themes of concern emerged, which are illustrated and reviewed: (1) family relations, (2) medical impact, (3) patients’ cognitive level, (4) agreements to be made in advance and organization of counseling, (5) disclosure to the child, and (6) need for follow-up. We conclude that discussing and carry...
Source: Journal of Inherited Metabolic Disease - April 18, 2018 Category: Internal Medicine Source Type: research

Molecular biology and gene therapy for glycogen storage disease type Ib
AbstractGlycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose-6-phosphate (G6P) transporter (G6PT or SLC37A4). The primary function of G6PT is to translocate G6P from the cytoplasm into the lumen of the endoplasmic reticulum (ER). Inside the ER, G6P is hydrolyzed to glucose and phosphate by either the liver/kidney/intestine-restricted glucose-6-phosphatase- α (G6Pase-α) or the ubiquitously expressed G6Pase-β. A deficiency in G6Pase-α causes GSD type Ia (GSD-Ia) and a deficiency in G6Pase-β causes GSD-I-related syndrome (GSD-Irs). In gluconeogen...
Source: Journal of Inherited Metabolic Disease - April 16, 2018 Category: Internal Medicine Source Type: research

Dental and periodontal manifestations of glycogen storage diseases: a case series of 60 patients
AbstractGlycogen storage diseases (GSDs) are rare genetic disorders of glycogen metabolism where the liver, kidneys, respiratory and cardiac muscles, as well as the immune and skeletal systems can be affected. Oral manifestations can also be present, but the specificity and frequency of these manifestations in the different forms of GSD are unknown. Analysis of a case series of 60 patients presenting four types of GSD (Ia, Ib, III, and IX) showed that the different types of GSDs have common and specific oral manifestations. In none of the GSD types studied, the prevalence of caries was higher than in the general population...
Source: Journal of Inherited Metabolic Disease - April 16, 2018 Category: Internal Medicine Source Type: research

The role of the Human Metabolome Database in inborn errors of metabolism
AbstractMetabolomics holds considerable promise to advance our understanding of human disease, including our understanding of inborn errors of metabolism (IEM). The application of metabolomics in IEM research has already led to the discovery of several novel IEMs and the identification of novel IEM biomarkers. However, with hundreds of known IEMs and more than 700 associated IEM metabolites, it is becoming increasingly challenging for clinical researchers to keep track of IEMs, their associated metabolites, and their corresponding metabolic mechanisms. Furthermore, when using metabolomics to assist in IEM biomarker discove...
Source: Journal of Inherited Metabolic Disease - April 16, 2018 Category: Internal Medicine Source Type: research

Recognizable phenotypes in CDG
AbstractPattern recognition, using a group of characteristic, or discriminating features, is a powerful tool in metabolic diagnostic. A classic example of this approach is used in biochemical analysis of urine organic acid analysis, where the reporting depends more on the correlation of pertinent positive and negative findings, rather than on the absolute values of specific markers. Similar uses of pattern recognition in the field of biochemical genetics include the interpretation of data obtained by metabolomics, like glycomics, where a recognizable pattern or the presence of a specific glycan sub-fraction can lead to the...
Source: Journal of Inherited Metabolic Disease - April 13, 2018 Category: Internal Medicine Source Type: research

Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult –onset type II citrullinemia
We present the therapy for six CTLN2 patients. All the patients’ general condition steadily improved and five patients with hyperammonemic encephalopathy recovered from unconsciousness in a few days. Before the treatment, plasma glutamine levels did not increase over the normal range and rather decreased to lower than the normal range in some patients. The treatment promptly decreased the blood ammonia leve l, which was accompanied by a decrease in plasma citrulline levels and an increase in plasma glutamine levels. These findings indicated that hyperammonemia was not only caused by the impairment of ureagenesis at A...
Source: Journal of Inherited Metabolic Disease - April 12, 2018 Category: Internal Medicine Source Type: research

The decision to discontinue screening for carnitine uptake disorder in New Zealand
AbstractWhen screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn screening (NBS) service identified infants as screen-positive if they had initial and repeat free carnitine (C0) levels of less than 5.0  μmol/L. Since 2006, the NBS service has identified two infants with biochemical and genetic features consistent with neonatal CUD and nine mothers with features consistent with maternal CUD. A review of the literature suggests that these nine women reflect less than half the true prevalence and t hat CUD is relatively common. However, the NZ results (two infants) suggest a very low sensitivit...
Source: Journal of Inherited Metabolic Disease - April 9, 2018 Category: Internal Medicine Source Type: research

Advances in computer-assisted syndrome recognition by the example of inborn errors of metabolism
AbstractSignificant improvements in automated image analysis have been achieved in recent years and tools are now increasingly being used in computer-assisted syndromology. However, the ability to recognize a syndromic facial gestalt might depend on the syndrome and may also be confounded by severity of phenotype, size of available training sets, ethnicity, age, and sex. Therefore, benchmarking and comparing the performance of deep-learned classification processes is inherently difficult. For a systematic analysis of these influencing factors we chose the lysosomal storage diseases mucolipidosis as well as mucopolysacchari...
Source: Journal of Inherited Metabolic Disease - April 5, 2018 Category: Internal Medicine Source Type: research

A preliminary study of telemedicine for patients with hepatic glycogen storage disease and their healthcare providers: from bedside to home site monitoring
ConclusionsThis report describes the design, development, and validation process of a telemedicine platform for patients with hepatic GSD. The GCP can facilitate home site monitoring and data exchange between patients with hepatic GSD and healthcare providers under varying circumstances. In the future, the GCP may support cross-border healthcare, second opinion processes and clinical trials, and could possibly also be adapted for other diseases for which a medical diet is the cornerstone. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 29, 2018 Category: Internal Medicine Source Type: research

Allogeneic hematopoietic cell transplantation in Farber disease
ConclusionAllogeneic HCT leads to complete and persistent resolution of the inflammatory aspects in FD patients. It appears to have no beneficial effect on progression of nervous system involvement. New mutations in the acid ceramidase gene were identified. A genotype/phenotype correlation could not be established. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 29, 2018 Category: Internal Medicine Source Type: research

The rendering of human phenotype and rare diseases in ICD-11
AbstractICD-11 (International Classification of Diseases, 11th Revision) is the next major revision of the ICD by the World Health Organization (WHO). ICD-11 differs dramatically from historical versions, as it is based on an underlying semantic network of terms and meaning, called the Foundation. To function as a mutually exclusive and exhaustive statistical classification, ICD-11 creates derivative linearizations from the network that is a monohierarchy with residual categories such as Not Elsewhere Classified. ICD-11 also introduces the widespread post-coordination of terms, which allows for highly expressive representa...
Source: Journal of Inherited Metabolic Disease - March 29, 2018 Category: Internal Medicine Source Type: research

Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders
ConclusionAlthough our data on 16 pregnancies in seven patients did not  present any association of standard drug treatment with an increased rate of pregnancy complications, abnormal obstetrical or paediatric outcome, an intensive clinical and biochemical supervision by a multidisciplinary team before, during and after the pregnancy in any BH4 deficiency is essential since available data on pregnancies in patients with BH4 deficiencies is limited. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

Newborn screening for Pompe disease: impact on families
AbstractPompe disease (PD) is an autosomal recessive lysosomal storage disorder causing progressive glycogen accumulation in muscles, with variability in age of onset and severity. For infantile-onset PD (IOPD), initiation of early treatment can be life-saving; however, current newborn screening (NBS) technology cannot distinguish IOPD from late-onset PD (LOPD) without clinical workup. Therefore, families of LOPD infants diagnosed by NBS may now spend years or even decades aware of their illness before symptoms appear, creating a pre-symptomatic awareness phase with which the medical community has little experience. The pr...
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

Identification and characterization of 40 novel hydroxymethylbilane synthase mutations that cause acute intermittent porphyria
AbstractAcute intermittent porphyria (AIP), an autosomal dominant disorder due to the half-normal activity of hydroxymethylbilane synthase (HMBS), is characterized by acute neurovisceral attacks that are precipitated by factors that induce heme biosynthesis. Molecular diagnosis is the most sensitive and specific diagnostic test for AIP, and importantly, it permits the identification of asymptomatic family members for genetic counseling and avoidance of precipitating factors. Here, we report the identification of 40 novelHMBS mutations, including 11 missense, four nonsense, 16 small insertions or deletions, eight consensus ...
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

The role of suboptimal mitochondrial function in vulnerability to post-traumatic stress disorder
AbstractPost-traumatic stress disorder remains the most significant psychiatric condition associated with exposure to a traumatic event, though rates of traumatic event exposure far outstrip incidence of PTSD. Mitochondrial dysfunction and suboptimal mitochondrial function have been increasingly implicated in several psychopathologies, and recent genetic studies have similarly suggested a pathogenic role of mitochondria in PTSD. Mitochondria play a central role in several physiologic processes underlying PTSD symptomatology, including abnormal fear learning, brain network activation, synaptic plasticity, steroidogenesis, a...
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

Non-osteogenic muscle hypertrophy in children with McArdle disease
ConclusionWe have identified a ‘non-osteogenic muscle hypertrophy’ in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

A family segregating lethal neonatal coenzyme Q 10 deficiency caused by mutations in COQ9
AbstractPrimary CoQ10 deficiency is a clinically and genetically heterogeneous, autosomal recessive disorder resulting from mutations in genes involved in the synthesis of coenzyme Q10 (CoQ10). To date, mutations in nine proteins required for the biosynthesis of CoQ10 cause CoQ10 deficiency with varying clinical presentations. In 2009 the first patient with mutations in COQ9 was reported in an infant with a neonatal-onset, primary CoQ10 deficiency with multi-system disease. Here we describe four siblings with a previously undiagnosed lethal disorder characterized by oligohydramnios and intrauterine growth restriction, vari...
Source: Journal of Inherited Metabolic Disease - March 20, 2018 Category: Internal Medicine Source Type: research

Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes
ConclusionCDCA may reverse the pathophysiological process in patients with CTX, especially if treatment is initiated early in the disease process. Besides tendon xanthoma, this study stresses the need to consider plasma cholestanol measurement in any patient with infantile chronic diarrhea and/or jaundice, juvenile cataract, learning disability and/or autism spectrum disorder, pyramidal signs, cerebellar syndrome or peripheral neuropathy. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 20, 2018 Category: Internal Medicine Source Type: research

Proposal for an individualized dietary strategy in patients with very long-chain acyl-CoA dehydrogenase deficiency
AbstractBackgroundPatients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments.ObjectiveTo define dietary strategies for individuals with VLCADD based on the predicted phenotype.MethodWe evaluated long-term dietary histories of a cohort of...
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Unraveling the unknown areas of the human metabolome: the role of infrared ion spectroscopy
AbstractThe identification of molecular biomarkers is critical for diagnosing and treating patients and for establishing a fundamental understanding of the pathophysiology and underlying biochemistry of inborn errors of metabolism. Currently, liquid chromatography/high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy are the principle methods used for biomarker research and for structural elucidation of small molecules in patient body fluids. While both are powerful techniques, several limitations exist that often make the identification of unknown compounds challenging. Here, we describe how infrar...
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Long-term follow-up of 17 patients with childhood Pompe disease treated with enzyme replacement therapy
AbstractObjectivesPompe disease is a progressive metabolic myopathy for which enzyme replacement therapy (ERT) was approved in 2006. While various publications have examined the effects of ERT in classic-infantile patients and in adults, little has been published on ERT in children with non-classic presentations.Study designThis prospective study was conducted from June 1999 to May 2015. Seventeen patients from various countries participated. Outcome measures comprised muscle function (6-minute walk test, quick motor-function test (QMFT)), muscle strength (hand-held dynamometry; manual muscle testing), and lung function (F...
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders
AbstractTandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of lysosomal storage disorders (LSDs) and how MS/MS has changed the diagnostic rationale in recent years. This fine technology brings more sensitive, specific, and reliable methods than the previous biochemical ones for the analysis of urinary glycosaminoglycans, oligosaccharides, and sialic acid. In sph...
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Think big — think omics
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 14, 2018 Category: Internal Medicine Source Type: research

Multiomics tools for the diagnosis and treatment of rare neurological disease
AbstractConventional workup of rare neurological disease is frequently hampered by diagnostic delay or lack of diagnosis. While biomarkers have been established for many neurometabolic disorders, improved methods are required for diagnosis of previously unidentified or underreported causes of rare neurological disease. This would result in a higher diagnostic yield and increased patient numbers required for interventional studies. Recent studies using next-generation sequencing and metabolomics have led to identification of novel disease-causing genes and biomarkers. This combined approach can assist in overcoming challeng...
Source: Journal of Inherited Metabolic Disease - March 13, 2018 Category: Internal Medicine Source Type: research

Promises and pitfalls of untargeted metabolomics
AbstractMetabolomics is one of the newer omics fields, and has enabled researchers to complement genomic and protein level analysis of disease with both semi-quantitative and quantitative metabolite levels, which are the chemical mediators that constitute a given phenotype. Over more than a decade, methodologies have advanced for both targeted (quantification of specific analytes) as well as untargeted metabolomics (biomarker discovery and global metabolite profiling). Untargeted metabolomics is especially useful when there is no a priori metabolic hypothesis. Liquid chromatography coupled to mass spectrometry (LC-MS) has ...
Source: Journal of Inherited Metabolic Disease - March 13, 2018 Category: Internal Medicine Source Type: research

Quantification of gait in children with mitochondrial disease
In conclusion, measuring spatiotemporal parameters of gait using the GAITRite in ambulatory children with mitochondrial disease is feasible and reliable for most of the parameters measured. When using gait analysis in future studies in children with mitochondrial disease, we advise i) to use an exercise test prior to the gait analysis, ii) to let children practice the test before the actual data collection, and iii) not to use symmetry parameters. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 12, 2018 Category: Internal Medicine Source Type: research

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders
In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 9, 2018 Category: Internal Medicine Source Type: research

The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders
In conclusion, in s evere neonatal onset hyperammonemia, the current practice of dialysis, which effectively clears ammonia, had no impact on outcome. It may be essential for improving outcome to initiate all available treatment options, including dialysis, as early as possible. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 8, 2018 Category: Internal Medicine Source Type: research

Tetrahydrobiopterin treatment reduces brain L-Phe but only partially improves serotonin in hyperphenylalaninemic ENU1/2 mice
AbstractHyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH4) treatment inPahenu1/enu2 (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type. We found that brain L-tyrosine, L-tryptophan, BH4 cofactor and catecholamine concentration...
Source: Journal of Inherited Metabolic Disease - March 8, 2018 Category: Internal Medicine Source Type: research

MPS-IIIA mice acquire autistic behaviours with age
In this study, we investigated whether a mouse model of MPS-IIIA exhibited ASD-like symptoms. The BTBR T+Itpr3tf/J inbred mouse model of autism was used as a positive control. Male MPS-IIIA and BTBR mice were less sociable compared with unaffected C57BL/6 male mice in the reciprocal social approach test administered at 20  weeks of age. Alternations in the frequency of social interactions was not evident at earlier stages of the disease course, suggesting an acquisition of ASD-like social behaviours. Stereotypical behaviours were not evident in male MPS-IIIA mice in the marble-burying test nor was the quality of nes t...
Source: Journal of Inherited Metabolic Disease - March 8, 2018 Category: Internal Medicine Source Type: research

Clinical glycomics for the diagnosis of congenital disorders of glycosylation
AbstractClinical glycomics comprises a spectrum of different analytical methodologies to analyze glycan structures, which provides insights into the mechanisms of glycosylation. Within clinical diagnostics, glycomics serves as a functional readout of genetic variants, and can form a basis for therapy development, as was described for PGM1-CDG. Integration of glycomics with genomics has resulted in the elucidation of previously unknown disorders of glycosylation, namely CCDC115-CDG, TMEM199-CDG, ATP6AP1-CDG, MAN1B1-CDG, and PGM1-CDG. This review provides an introduction into protein glycosylation and presents the different ...
Source: Journal of Inherited Metabolic Disease - March 1, 2018 Category: Internal Medicine Source Type: research

Mulberries in the urine: a tell-tale sign of Fabry disease
This report emphasizes the usefulness of urinary microscopic findings in the early diagnosis of Fabry disease. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - February 27, 2018 Category: Internal Medicine Source Type: research

Natural history of neurological abnormalities in cerebrotendinous xanthomatosis
ConclusionWe provide estimates for the neurological progression of CTX, categorizing neurological abnormalities according to time and probability of development. Our approach may be applicable to other rare disorders. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - February 26, 2018 Category: Internal Medicine Source Type: research

A SEPSECS mutation in a 23-year-old woman with microcephaly and progressive cerebellar ataxia
AbstractMutations in theSEPSECS gene are associated with pontocerebellar hypoplasia type 2D. Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare autosomal recessive neurodegenerative disorders, mainly affecting pons and cerebellum. Patients have severe motor and cognitive impairments and often die during infancy. Here, we report a 23-year-old woman with slowly progressive cerebellar ataxia and cognitive impairment, in whom a homozygous missense mutation in theSEPSECS gene (c.1321G>A; p.Gly441Arg) was identified with whole exome sequencing. Our findings underline that defects in selenoprotein synthesis can ...
Source: Journal of Inherited Metabolic Disease - February 20, 2018 Category: Internal Medicine Source Type: research