Parent knowledge regarding food selection for children with PKU: Results of a survey in the United States.

Objectives: Dietary treatment is the main therapy for most patients with phenylketonuria (PKU). Parental knowledge regarding food selection is crucial to ensure adequate metabolic control and brain development during childhood and to promote lifelong adherence and healthy dietary behavior in the offspring. The aims of this study were to assess whether parental or caregiver knowledge regarding nutritional selection for children with PKU is in accordance with medical recommendations and to evaluate factors that influence their level of knowledge.

Reinstitution of pegvaliase therapy during lactation.

Pegvaliase, an injectable form of phenylalanine ammonia lyase, is an enzyme substitution therapy for adults with phenylketonuria (PKU). Experience with pegvaliase during lactation is scarce. Limited evidence suggests that pegvaliase does not pass into breast milk.

Review of neuropsychological outcomes in isolated methylmalonic acidemia: recommendations for assessing impact of treatments.

Methylmalonic acidemia (MMA) due to methylmalonyl-CoA mutase deficiency (OMIM #251,000) is an autosomal recessive disorder of organic acid metabolism associated with life-threatening acute metabolic decompensations and significant neuropsychological deficits. "Isolated" MMA refers to the presence of excess methylmalonic acid without homocysteine elevation. Belonging to this class of disorders are those that involve complete deficiency (mut) and partial deficiency (mut) of the methylmalonyl-CoA mutase enzyme and other disorders causing excess methylmalonic acid excretion.

Analysis of cognitive ability and adaptive behavior assessment tools used in an observational study of patients with mucopolysaccharidosis II.

Background: Mucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by cognitive impairment in most patients. This post hoc analysis evaluated changes in cognitive function, adaptive behavior and functional outcomes in patients with neuronopathic MPS II over time. Fifty-five children with MPS II were enrolled in a 24-month observational study (NCT01822184).

Adaptation and Validation of a Questionnaire to Evaluate Knowledge of the Low Phe Diet in PKU.

Phenylketonuria (PKU) is an autosomal recessive disorder of phenylalanine (Phe) metabolism, causing a build-up of Phe in the body. Treatment consists of a Phe-restricted diet for life and regular determination of blood Phe levels to monitor the intake of Phe. Despite the fact that diet is the cornerstone of treatment, there are no studies examining common knowledge about food items and whether they are allowed as part of the PKU diet.

Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project: A Randomized Clinical Trial.

Importance: Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families.

Objective: To assess the psychosocial effect of nGS on families from the BabySeq Project, a randomized clinical trial evaluating the effect of nGS on the clinical care of newborns from well-baby nurseries and intensive care units.

Design, Setting, And Participants: In this randomized clinical trial conducted from May 14, 2015, to May 21, 2019, at well-baby nurseries and intensive care units at 3 Boston, Massachusetts, area hospitals, 519 parents of 325 infants completed surveys at enrollment, immediately after disclosure of nGS results, and 3 and 10 months after results disclosure.

Transient developmental delays in infants with Duarte-2 variant galactosemia.

Duarte galactosemia is not classic galactosemia, but rather an example of biochemical variant galactosemia that results in approximately 25% residual activity of galactose-1-phosphate uridylyltransferase (GALT) enzyme. In contrast, classic galactosemia is associated with complete or near complete absence of GALT activity. While infants with classic galactosemia are placed on galactose-restricted diets to prevent the acute and long-term manifestations of their metabolic disorder, while individuals with Duarte variant galactosemia (Duarte-2 galactosemia) do not require diet therapy.

Effects of participation in a U.S. trial of newborn genomic sequencing on parents at risk for depression.

Much emphasis has been placed on participant's psychological safety within genomic research studies; however, few studies have addressed parental psychological health effects associated with their child's participation in genomic studies, particularly when parents meet the threshold for clinical concern for depression. We aimed to determine if parents' depressive symptoms were associated with their child's participation in a randomized-controlled trial of newborn exome sequencing. Parents completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline, immediately post-disclosure, and 3 months post-disclosure.

Person Ability Scores as an Alternative to Norm-Referenced Scores as Outcome Measures in Studies of Neurodevelopmental Disorders.

Although norm-referenced scores are essential to the identification of disability, they possess several features which affect their sensitivity to change. Norm-referenced scores often decrease over time among people with neurodevelopmental disorders who exhibit slower-than-average increases in ability. Further, the reliability of norm-referenced scores is lower at the tails of the distribution, resulting in floor effects and increased measurement error for people with neurodevelopmental disorders.

Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia.

Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose-free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.

Developmental Support for Infants With Genetic Disorders.

As the technical ability for genetic diagnosis continues to improve, an increasing number of diagnoses are made in infancy or as early as the neonatal period. Many of these diagnoses are known to be associated with developmental delay and intellectual disability, features that would not be clinically detectable at the time of diagnosis. Others may be associated with cognitive impairment, but the incidence and severity are yet to be fully described.

Neuropsychological attributes of urea cycle disorders: A systematic review of the literature.

Urea cycle disorders (UCDs) are rare inherited metabolic conditions that impair the effectiveness of the urea cycle responsible for removing excess ammonia from the body. The estimated incidence of UCDs is 1:35 000 births, or approximately 113 new patients with UCD per year. This review summarizes neuropsychological outcomes among patients with the eight UCDs in reports published since 1980.

Phenotypic variability in deficiency of the α subunit of succinate-CoA ligase.

Succinyl-CoA synthetase or succinate-CoA ligase deficiency can result from biallelic mutations in gene that encodes for the alpha subunit of the succinyl-CoA synthetase. Mutations in this gene were initially associated with fatal infantile lactic acidosis. We describe an individual with a novel biallelic pathogenic mutation in with a less severe phenotype dominated by behavioral problems.

The ability of an LC-MS/MS-based erythrocyte GALT enzyme assay to predict the phenotype in subjects with GALT deficiency.

Background: GALT deficiency is a rare genetic disorder of carbohydrate metabolism. Due to the decreased activity or absence of the enzyme galactose-1-phosphate uridylyltransferase (GALT), cells from affected individuals are unable to metabolize galactose normally. Lactose consumption in the newborn period could potentially lead to a lethal disease process with multi-organ involvement.

Impairment of cognitive function in ornithine transcarbamylase deficiency is global rather than domain-specific and is associated with disease onset, sex, maximum ammonium, and number of hyperammonemic events.

Beginning in 2006, the Urea Cycle Disorders Consortium (UCDC) has conducted a longitudinal study of eight inherited deficiencies of enzymes and transporters of the urea cycle, including 444 individuals with ornithine transcarbamylase deficiency (OTCD), of whom 300 (67 males, 233 females) received psychological evaluation. In a cross-sectional study (age range, 3-71 years), analysis of covariance (ANCOVA) determined the association between outcomes in five cognitive domains (global intelligence, executive functions, memory, visuomotor integration, visual perception) and sex, age at testing and timing of disease onset defined as early onset (≤28 days; EO), late onset (LO), or asymptomatic (AS). The dataset of 183 subjects with complete datasets (31 males, 152 females) revealed underrepresentation of EO subjects (2 males, 4 females), who were excluded from the ANCOVA.

Revising the Psychiatric Phenotype of Homocystinuria.

Purpose: Associations of psychiatric and psychological symptoms with homocystinuria (HCU) have been described in multiple reports. This retrospective study was undertaken to refine the psychological phenotype among HCU patients and identify biomedical markers that could be used for prediction of those psychiatric or psychological symptoms.

Methods: This study examines the prevalence of psychological symptoms within a sample of 25 patients with classical homocystinuria.

Parental interest in genomic sequencing of newborns: enrollment experience from the BabySeq Project.

Purpose: Newborn genomic sequencing (nGS) has great potential to improve pediatric care. Parental interest and concerns about genomics are relatively unexplored. Understanding why parents decline research consent for nGS may reveal implementation barriers.

The BabySeq project: implementing genomic sequencing in newborns.

Background: The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The "BabySeq Project" is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.

Methods: Families of newborns are enrolled from Boston Children's Hospital and Brigham and Women's Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants.

Biochemical markers and neuropsychological functioning in distal urea cycle disorders.

Urea cycle disorders often present as devastating metabolic conditions, resulting in high mortality and significant neuropsychological damage, despite treatment. The Urea Cycle Disorders Longitudinal Study is a natural history study that collects data from regular clinical follow-up and neuropsychological testing. This report examines links between biochemical markers (ammonia, glutamine, arginine, citrulline) and primary neuropsychological endpoints in three distal disorders, argininosuccinic acid synthetase deficiency (ASD or citrullinemia type I), argininosuccinic acid lyase deficiency (ASA or ALD), and arginase deficiency (ARGD).

Liver Failure as the Presentation of Ornithine Transcarbamylase Deficiency in a 13-Month-Old Female.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle disorder with variable expressivity in heterozygous females. While liver function testing is often abnormal in patients with OTCD, liver failure is uncommon on presentation. A 13-month-old female with no significant past medical history presented with irritability, right arm weakness, and decreased appetite.

Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations.

Tyrosinemia type I (hepatorenal tyrosinemia, HT-1) is an autosomal recessive condition resulting in hepatic failure with comorbidities involving the renal and neurologic systems and long term risks for hepatocellular carcinoma. An effective medical treatment with 2-[2-nitro-4-trifluoromethylbenzoyl]-1,3-cyclohexanedione (NTBC) exists but requires early identification of affected children for optimal long-term results. Newborn screening (NBS) utilizing blood succinylacetone as the NBS marker is superior to observing tyrosine levels as a way of identifying neonates with HT-1.

Treatment adherence during childhood in individuals with phenylketonuria: Early signs of treatment discontinuation.

Introduction: Phenylketonuria (PKU) is an autosomal recessive disorder characterized by a deficiency in phenylalanine (Phe) hydroxylase activity. Early diagnosis and continuous treatment with a low Phe diet prevents severe neurological and cognitive impairment.

Aims: 1.