Inborn Errors Of Metabolism Presenting Research Articles

Cobalamin C Deficiency, an Inborn Error of Metabolism presenting with Subacute Neuropsychiatric Symptoms (P9-4.001)

<h3>Objective:</h3> Inpatient Neurology teams are often consulted to rule out neurological causes for new-onset neuropsychiatric symptoms. This case highlights the importance of considering possible Inborn Errors of Metabolism (IEM) that require specific treatments, and avoiding premature closure on a primary psychiatric disorder. <h3>Background:</h3> A 15-year-old presented to a pediatric hospital with a 4–8 week onset of neuropsychiatric (psychosis, psychomotor slowing, catatonia, sleep cycle irregularities, and tremors) and systemic (acute on chronic kidney injury and hypertension) symptoms. Neurology was consulted for further evaluation. In addition to the abnormal higher mental function exam, the neurological exam was significant for hyperreflexia in both the upper and lower extremities. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> Neuroimaging (an initial non-contrast CT Head and MRI brain with and without contrast) did not reveal an intracranial abnormality. Analysis of cerebrospinal fluid, including an autoimmune encephalitis panel, was unremarkable. Metabolic testing was significant for elevated homocysteine and methylmalonic aciduria with normal Vitamin B12 levels. Genetics and metabolic consult recommended testing for Cobalamin C deficiency that returned positive with pathogenic mutations in MMACHC gene. Neuropsychiatric symptoms began to improve after the initiation of treatment with hydroxocobalamin, carnitine, betaine, and leucovorin. <h3>Conclusions:</h3> Cobalamin C deficiency (CblC) most commonly presents in infants less than 1 year, but is also known to present rarely in adolescence or adulthood, most commonly with subacute onset psychiatric symptoms, myelopathy, and cardiovascular disease. CblC is an autosomal recessive disorder caused most commonly by pathogenic variants within the MMACHC gene. Late-onset forms of IEM can present with isolated neuropsychiatric symptoms years after birth and thus are prone to be missed. Treatable metabolic disorders should be considered in the workup for new-onset neuropsychiatric symptoms. <b>Disclosure:</b> Dr. Engel has nothing to disclose. Dr. Rashid has nothing to disclose. Dr. Al-Beshri has nothing to disclose. Dr. Ananth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Reata Therapeutics. The institution of Dr. Ananth has received research support from Acadia Pharmaceuticals.

Adult GAMT deficiency: A literature review and report of two siblings

Guanidinoacetate methyltransferase (GAMT) deficiency is a creatine deficiency disorder and an inborn error of metabolism presenting with progressive intellectual and neurological deterioration. As most cases are identified and treated in early childhood, adult phenotypes that can help in understanding the natural history of the disorder are rare. We describe two adult cases of GAMT deficiency from a consanguineous family in Pakistan that presented with a history of global developmental delay, cognitive impairments, excessive drooling, behavioral abnormalities, contractures and apparent bone deformities initially presumed to be the reason for abnormal gait. Exome sequencing identified a homozygous nonsense variant in GAMT: NM_000156.5:c.134G>A (p.Trp45*). We also performed a literature review and compiled the genetic and clinical characteristics of all adult cases of GAMT deficiency reported to date. When compared to the adult cases previously reported, the musculoskeletal phenotype and the rapidly progressive nature of neurological and motor decline seen in our patients is striking. This study presents an opportunity to gain insights into the adult presentation of GAMT deficiency and highlights the need for in-depth evaluation and reporting of clinical features to expand our understanding of the phenotypic spectrum.

Validation of the EULAR/ACR 2017 idiopathic inflammatory myopathy classification criteria in juvenile dermatomyositis patients

In 2017, a new set of criteria was proposed by EULAR/ACR to classify idiopathic inflammatory myopathies. Our aim was to validate the EULAR/ACR 2017 classification criteria in juvenile dermatomyositis (JDM) patients. This study was carried out at Hacettepe University Children's Hospital Department of Paediatrics, Divisions of Rheumatology, Neurology and Paediatric Pathology Unit. Control patients included inborn errors of metabolism presenting with myopathy and/or rhabdomyolysis, idiopathic rhabdomyolysis, dystrophinopathies, neuromyotonia and systemic rheumatic disorders. Patients' data were collected retrospectively from patient files. Fifty-eight JDM patients (60.3% female) and 40 controls (32.5% female) were included in this study. When the probability cut-off was set at 55% as recommended, the sensitivity/specificity of the new criteria to diagnose JDM were 96.5%/85% in the total cohort, 95.8%/84.6% without the muscle biopsy data and 97%/85.7% with biopsy data. With the ROC curve analysis, the optimal probability cut-off for the whole cohort was found to be >62%; providing a sensitivity/specificity of 96.6% (95% CI: 88.1% to 99.6)/90% (95% CI: 76.3% to 97.2%), and >68.5% for the patients with muscle biopsy providing sensitivity/specificity of 97% (84.7-99.9%)/100% (76.8-100%), respectively. The new EULAR/ACR criteria were the most sensitive, however, the least specific compared to the Tanimoto criteria (sensitivity/specificity 64%/97.5%) and Bohan-Peter criteria (sensitivity/ specificity 74.1%/92.5%). The new EULAR/ACR criteria performed favourably in our JDM cohort especially with the probability cut-off of >62%.

A Proposed Diagnostic Algorithm for Inborn Errors of Metabolism Presenting With Movements Disorders.

Inherited metabolic diseases or inborn errors of metabolism frequently manifest with both hyperkinetic (dystonia, chorea, myoclonus, ataxia, tremor, etc.) and hypokinetic (rigid-akinetic syndrome) movement disorders. The diagnosis of these diseases is in many cases difficult, because the same movement disorder can be caused by several diseases. Through a literature review, two hundred and thirty one inborn errors of metabolism presenting with movement disorders have been identified. Fifty-one percent of these diseases exhibits two or more movement disorders, of which ataxia and dystonia are the most frequent. Taking into account the wide range of these disorders, a methodical evaluation system needs to be stablished. This work proposes a six-step diagnostic algorithm for the identification of inborn errors of metabolism presenting with movement disorders comprising red flags, characterization of the movement disorders phenotype (type of movement disorder, age and nature of onset, distribution and temporal pattern) and other neurological and non-neurological signs, minimal biochemical investigation to diagnose treatable diseases, radiological patterns, genetic testing and ultimately, symptomatic, and disease-specific treatment. As a strong action, it is emphasized not to miss any treatable inborn error of metabolism through the algorithm.

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr.

PROFILE AND OUTCOME OF CHILDREN WITH INBORN ERRORS OF METABOLISM IN A TERTIARY PEDIATRIC INTENSIVE CARE UNIT IN SOUTH INDIA

Introduction: Inborn errors of metabolism (IEM) can present as acute metabolic emergencies resulting in significant morbidity or death. Good intensive care supportive management and specific metabolic crisis treatment by tertiary pediatric intensive care unit (PICU) play a crucial role in optimizing the outcomes. Objectives: We aimed to study the clinical profile and outcome of children with IEM presenting as an acute metabolic crisis in a tertiary PICU. Methods: This retrospective descriptive study was conducted in a tertiary care center in south India between June 2016 and December 2018. We included children admitted in PICU as medical emergency and diagnosed to have IEM either earlier or at the time of PICU presentation by biochemical testing (basic testing and tandem mass spectrometry [TMS], gas chromatography-mass spectrometry [GCMS] and high-performance liquid chromatography [HPLC], and/or specialized testing) and/or molecular analysis. Clinical profile, details of diagnostic workup, and outcome were collected and analyzed. Results: Out of 2815 children admitted in PICU, 15 had IEM (0.9%). Median (interquartile range) age of presentation was 15 months (10–30 months). Consanguinity was found in 80%. The most common disorder was protein metabolic disorder. Seven patients were diagnosed in the newborn period, five during evaluation for developmental delay before PICU admission, and three were newly diagnosed during PICU admission. Supportive therapy of invasive/non-invasive ventilation and peritoneal dialysis was initiated in 10 and 4, respectively. Special formula was started in nine patients. Five (33%) died in spite of intensive care management. TMS, GCMS, and HPLC yielded definitive diagnosis in 12 (80%) patients. Molecular analysis was done in 12 patients. Conclusion: The most common cause for metabolic crisis in PICU is due to protein metabolic disorder. Aggressive intensive care and IEM directed therapy can be lifesaving, but still, the mortality is high.

Persistent Hypoglycemia in Children: Targeted Gene Panel Improves the Diagnosis of Hypoglycemia Due to Inborn Errors of Metabolism

To evaluate the role of next generation sequencing in genetic diagnosis of pediatric patients with persistent hypoglycemia. Sixty-four patients investigated through an extensive workup were divided in 3 diagnostic classes based on the likelihood of a genetic diagnosis: (1) single candidate gene (9/64); (2) multiple candidate genes (43/64); and (3) no candidate gene (12/64). Subsequently, patients were tested through a custom gene panel of 65 targeted genes, which included 5 disease categories: (1) hyperinsulinemic hypoglycemia, (2) fatty acid-oxidation defects and ketogenesis defects, (3) ketolysis defects, (4) glycogen storage diseases and other disorders of carbohydrate metabolism, and (5) mitochondrial disorders. Molecular data were compared with clinical and biochemical data. A proven diagnosis was obtained in 78% of patients with suspicion for a single candidate gene, in 49% with multiple candidate genes, and in 33% with no candidate gene. The diagnostic yield was 48% for hyperinsulinemic hypoglycemia, 66% per fatty acid-oxidation and ketogenesis defects, 59% for glycogen storage diseases and other carbohydrate disorders, and 67% for mitochondrial disorders. This approach provided a diagnosis in ~50% of patients in whom clinical and laboratory evaluation did not allow identification of a single candidate gene and a diagnosis was established in 33% of patients belonging to the no candidate gene class. Next generation sequencing technique is cost-effective compared with Sanger sequencing of multiple genes and represents a powerful tool for the diagnosis of inborn errors of metabolism presenting with persistent hypoglycemia.

Contemporary scope of inborn errors of metabolism involving epilepsy or seizures.

Many inborn errors of metabolism may present with epilepsy or seizures, however, current scope of these diseases is unknown. Due to available precision medicine approaches in many inborn errors of metabolism and sophisticated traditional diagnostics, this group of disorders is of special relevance to clinicians. Besides, as current treatment is challenging and unsuccessful in more than 30% of all epilepsy patients, these diseases may provide valuable models for ictogenesis and epileptogenesis studies and potentially pave the ways to identification of novel treatments. The aim of this study was to elucidate genetic architecture of inborn errors of metabolism involving epilepsy or seizures and to evaluate their diagnostic approaches. After extensive search, 880 human genes were identified with a considerable part, 373 genes (42%), associated with inborn errors of metabolism. The most numerous group comprised disorders of energy metabolism (115, 31% of all inborn errors of metabolism). A substantial number of these diseases (26%, 97/373) have established specific treatments, therefore timely diagnosis comes as an obligation. Highly heterogenous, overlapping and non-specific phenotypes in most of inborn errors of metabolism presenting with epilepsy or seizures usually preclude phenotype-driven diagnostics. Besides, as traditional diagnostics involves a range of specialized metabolic tests with low diagnostic yields and is generally inefficient and lengthy, next-generation sequencing-based methods were proposed as a cost-efficient one-step way to shorten "diagnostic odyssey". Extensive list of 373 epilepsy- or seizures-associated inborn errors of metabolism genes may be of value in development of gene panels and as a tool for variants' filtration.

Next generation sequencing in pediatric hepatology and liver transplantation

Next generation sequencing (NGS) has revolutionized the analysis of human genetic variations, offering a highly cost-effective way to diagnose monogenic diseases (MDs). Because nearly half of the children with chronic liver disorders have a genetic cause and approximately 20% of pediatric liver transplantations are performed in children with MDs, NGS offers the opportunity to significantly improve the diagnostic yield in this field. Among the NGS strategies, the use of targeted gene panels has proven useful to rapidly and reliably confirm a clinical suspicion, whereas the whole exome sequencing (WES) with variants filtering has been adopted to assist the diagnostic workup in unclear clinical scenarios. WES is powerful but challenging because it detects a great number of variants of unknown significance that can be misinterpreted and lead to an incorrect diagnosis. In pediatric hepatology, targeted NGS can be very valuable to discriminate neonatal/infantile cholestatic disorders, disclose genetic causes of acute liver failure, and diagnose the subtype of inborn errors of metabolism presenting with a similar phenotype (such as glycogen storage disorders, mitochondrial cytopathies, or nonalcoholic fatty liver disease). The inclusion of NGS in diagnostic processes will lead to a paradigm shift in medicine, changing our approach to the patient as well as our understanding of factors affecting genotype-phenotype match. In this review, we discuss the opportunities and the challenges offered nowadays by NGS, and we propose a novel algorithm for cholestasis of infancy adopted in our center, including targeted NGS as a pivotal tool for the diagnosis of liver-based MDs. Liver Transplantation 24 282-293 2018 AASLD.

Thirteen year retrospective review of the spectrum of inborn errors of metabolism presenting in a tertiary center in Saudi Arabia.

BackgroundInborn errors of metabolism (IEMs) are individually rare; however, they are collectively common. More than 600 human diseases caused by inborn errors of metabolism are now recognized, and this number is constantly increasing as new concepts and techniques become available for identifying biochemical phenotypes. The aim of this study was to determine the type and distribution of IEMs in patients presenting to a tertiary care center in Saudi Arabia. METHOD: We conducted a retrospective review of children diagnosed with IEMs presenting to the Pediatric Department of King Abdulaziz Medical City in Riyadh, Saudi Arabia over a 13-year period.ResultsOver the 13- year period of this retrospective cohort, the total number of live births reached 110,601. A total of 187 patients were diagnosed with IEMs, representing a incidence of 169 in 100,000 births (1:591). Of these, 121 patients (64.7 %) were identified to have small molecule diseases and 66 (35.3 %) to have large molecule diseases. Organic acidemias were the most common small molecule IEMs, while lysosomal storage disorders (LSD) were the most common large molecule diseases. Sphingolipidosis were the most common LSD.ConclusionOur study confirms the previous results of the high rate of IEMs in Saudi Arabia and urges the health care strategists in the country to devise a long-term strategic plan, including an IEM national registry and a high school carrier screening program, for the prevention of such disorders. In addition, we identified 43 novel mutations that were not described previously, which will help in the molecular diagnosis of these disorders.

Lysosomal acid lipase deficiency in Greece: A rare inborn error of metabolism presenting with dyslipidaimia and liver disease

Lysosomal acid lipase deficiency in Greece: A rare inborn error of metabolism presenting with dyslipidaimia and liver disease

Treatable inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review.

BackgroundInborn errors of metabolism (IEMs) have been anecdotally reported in the literature as presenting with features of cerebral palsy (CP) or misdiagnosed as ‘atypical CP’. A significant proportion is amenable to treatment either directly targeting the underlying pathophysiology (often with improvement of symptoms) or with the potential to halt disease progression and prevent/minimize further damage.MethodsWe performed a systematic literature review to identify all reports of IEMs presenting with CP-like symptoms before 5 years of age, and selected those for which evidence for effective treatment exists.ResultsWe identified 54 treatable IEMs reported to mimic CP, belonging to 13 different biochemical categories. A further 13 treatable IEMs were included, which can present with CP-like symptoms according to expert opinion, but for which no reports in the literature were identified. For 26 of these IEMs, a treatment is available that targets the primary underlying pathophysiology (e.g. neurotransmitter supplements), and for the remainder (n = 41) treatment exerts stabilizing/preventative effects (e.g. emergency regimen). The total number of treatments is 50, and evidence varies for the various treatments from Level 1b, c (n = 2); Level 2a, b, c (n = 16); Level 4 (n = 35); to Level 4–5 (n = 6); Level 5 (n = 8). Thirty-eight (57%) of the treatable IEMs mimicking CP can be identified by ready available metabolic screening tests in blood or urine, while the remaining IEMs require more specific and sometimes invasive tests.ConclusionsLimited by the rare nature of IEMs and incomplete information in the literature, we conclude that (1) A surprisingly large number of IEMs can present with CP symptoms, as ‘CP mimics’, (2) although individually rare, a large proportion of these diseases are treatable such that neurological damage can either be reversed or prevented, (3) clinician awareness of treatable CP mimics is important for appropriate screening, diagnosis, and early intervention, and (4) systematic studies are required to elucidate the collective frequency of treatable IEMs in CP.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0197-2) contains supplementary material, which is available to authorized users.

Isolated mild intellectual disability expands the aminoacylase 1 phenotype spectrum.

Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism presenting with heterogeneous neurological symptoms such as psychomotor delay, seizures, intellectual disability and it is characterized by increased urinary excretion of N-acetylated amino acids. We report on a new patient who presented ACY1 deficiency in association with isolated mild intellectual disability, but neither neurological symptoms nor autistic features. The child showed a compound heterozygous mutation (p.Glu233Asp) and a novel p.Ser192Arg fs*64, predicting an unstable transcript and resulting in very low protein levels.This new ACY1 deficient child was identified through regular screening for inborn error of metabolism adopted in our department in all cases of intellectual disability. This report supports a recommendation to perform metabolic investigations in patients with isolated mild intellectual disability.

Congenital Genetic Inborn Errors of Metabolism Presenting as an Adult or Persisting Into Adulthood: Neuroimaging in the More Common or Recognizable Disorders

Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been identified and characterized in detail within recent decades, with promising therapeutic options. Neuroimaging is becoming increasingly utilized in earlier stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so as to monitor disease progress and treatment response. This review attempts to summarize in a concise fashion the neuroimaging findings of various CIEMs that may present in adulthood, as well as those that may persist into adulthood, whether because of beneficial therapy or a delay in diagnosis. Notably, some of these disorders have neuroimaging findings that differ from their classic infantile or early childhood forms, whereas others are identical to their early pediatric forms. The focus of this review is their appearance on routine magnetic resonance imaging sequences, with some basic attention to the findings of such CIEMs on specialized neuroimaging, based on recent or preliminary research. The general classes of disorders covered in this complex review are: peroxisomal disorders (adrenoleukodystrophy), lysosomal storage disorders (including metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry, Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases), mitochondrial disorders (including mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers, Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3-methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia, proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric acidurias), cytoskeletal or transporter molecule defects (including Alexander or fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher, Wilson, and Huntington diseases), and several neurodegenerative disorders of brain iron accumulation. Additionally, an arbitrary "miscellaneous" category of 5 recognizable disorders that may present in or persist into adulthood is summarized, which include megalencephalic leukoencephalopathy with subcortical cysts (megancephalic leukoencephalopathy with subcortical cysts or van der Knaap disease), polymerase-III gene defect ("4H syndrome"), childhood ataxia with central nervous system hypomyelination ("vanishing white matter disease"), striopallidodentate calcinosis ("Fahr disease"), and Cockayne syndrome.

Neuropsychiatric Symptoms in Inborn Errors of Metabolism: Incorporation of Genomic and Metabolomic Analysis into Therapeutics and Prevention.

Inborn errors of metabolism may present as a spectrum ranging from neonatal lethality to non-specific symptoms. Neuropsychiatric manifestations have been identified in three groups: those presenting as emergencies, those with chronic fluctuating symptoms, and those associated with mental retardation. Milder central nervous system specific inborn errors of metabolism may also present later in life with isolated psychiatric symptoms. Inborn errors of metabolism presenting with neuropsychiatric symptoms are described with illustrative case examples. Metabolomic and genomic approaches to identification and treatment are described.

Inborn Errors of Metabolism Presenting in Childhood

Neurodegenerative and neurometabolic disorders may cause significant morbidity and mortality in children. Imaging is important in early diagnosis of metabolic disorders and in determining the extent of brain injury. Especially after the development of new techniques such as diffusion-weighted magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), neuroimaging plays more important role in the diagnosis and management of these disorders. In these disorders, usually a mutation causes a clinically significant block in one or more metabolic pathways. This blockage usually results in either a deficiency of the product or in an accumulation of substrate with damage induced by either storage or toxicity. The presenting symptoms are usually nonspecific. In some of the metabolic disorders, long-term dietary or medical treatment options are available, and to make an early diagnosis in these disorders is important before the brain damage occurs. Prompt diagnosis, particularly in treatable disorders, is crucial to prevent neurological sequelae or death. If treatment is indeed available, neuroimaging also provides a baseline in evaluation of the efficacy of treatment. Therefore, the neuroradiologist should be aware of these disorders to prevent devastating results of delayed diagnosis. Metabolic disorders affecting the central nervous system, both gray and white matter can be classified by involvement of the primary cellular organelle as lysosomal, peroxisomal, mitochondrial disorders, or biochemical classification can be made as amino acid and organic acid metabolism defects or primary white matter disorders. This article presents the neuroimaging features of relatively more common metabolic disorders.

Approach to Management of Inborn Errors of Metabolism

This article reviewed the pathophysiology, diagnostic approach based on age of presentation and symptom complex, neonatal screening strategies, methods of obtaining and handling of samples and management of metabolic emergencies while awaiting results of investigations. The principles of long-term therapy, prevention and future prospects of IEMwere also discussed. Inborn errors of metabolism (IEM) must be considered in the differential diagnosis of critically ill neonates and infants with severe hypoglycaemia, encephalopathy, acidaemia, conjugated hyperbilirubinaemia or hyperammonaemia for which there is no apparent cause after a conventional work-up. Investigation is initiated by screening tests which includes blood glucose, ammonia, amino acids, urea and electrolytes levels, liver function tests and blood gases. Urinalysis for ketones, reducing substances, amino acids and organic acids is a very useful diagnostic tool. In neonates, ketonuria with acidosis is a very important laboratory finding pointing to IEM. Although the prognosis for patients with IEM presenting in the neonatal and early infancy period is often poor, every effort must be made to establish the diagnosis for parental counselling and in case prenatal diagnosis is possible in futurepregnancies. In conclusion, when presented with an ill full-term neonate, pursue the usual bacterial septicaemia work-up but do not neglect evaluation for metabolic disease.Keywords: Inborn errors, hereditary metabolic disorders, neonatal screening.

Congenital disorders of glycosylation: a rare cause of nephrotic syndrome

Congenital disorders of glycosylation (CDG) are inborn errors of metabolism presenting with multi-system organ involvement due to defective glycosylation of glycoproteins. We report here a case of microcephaly, hypotonia, seizure disorder and severe developmental delay since infancy in whom screening for CDG with transferring isoelectric focussing (TIEF) revealed a type I pattern. Following investigation, the specific defect in glycosylation remains to be identified; hence, a diagnosis of CDG Ix (type unknown) was made. At the age of 15-months the patient developed nephrotic syndrome and renal biopsy indicated a histopathological diagnosis of diffuse mesangial sclerosis on histopathology. Since cases of CDG Ix may often develop hypoalbuminaemia secondary to malabsorption or liver disease, this case highlights the need for additional regular monitoring for glomerular proteinuria, and indicates that a diagnosis of nephrotic syndrome should be considered in all types of CDG. Furthermore, we propose that early treatment with anti-proteinuric agents may be necessary to limit proteinuria and slow disease progression.

Approach to inborn errors of metabolism presenting in the neonate

Inborn errors of metabolism (IEM) are an important cause of acute illness in newborns. Presentation may mimic common neonatal conditions such as sepsis. Prompt detection requires a high index of suspicion and the early measurement of biochemical markers such as blood ammonia. Diagnosis is important not only for treatment but also for genetic counselling. Guidelines for diagnosis and early management of IEM presenting in the neonatal period are described.

Opsoclonus in a Neonate with Nonketotic Hyperglycinemia

Nonketotic hyperglycinemia (NKG) is a non-acidotic, non-hyperammonemic inborn error of metabolism presenting in the neonatal period. Often babies with NKG present in the first week of life with altered sensorium, seizures, apnea and respiratory failure (1, 2). Definite diagnosis is possible with CSF to glycine ratio and estimation of glycine cleaving enzyme levels in the liver. Here we report Opsoclonus in a baby with NKG.