Grip strength in patients with galactosemia and in a galactose-1-phosphate uridylyltransferase (GALT)-null rat model.

Classic galactosemia (CG) and clinical variant galactosemia (CVG) are allelic inborn errors of metabolism that result from profound deficiency, and near-profound deficiency, respectively, of galactose-1-P uridylyltransferase (GALT). Despite early detection and lifelong dietary restriction of galactose, which is the current standard of care, most patients with CG/CVG grow to experience a range of long-term developmental and other complications. One of the less well-understood complications of CG/CVG is decreased hand grip strength, as reported by Potter et al. (2013). Here, we confirm this phenotype in an independent cohort of 36 cases (4-18 years) and 19 controls (4-17 years), and further demonstrate that the grip strength deficit observed in cases may be secondary to growth delay. Specifically, we found that when grip strength of cases and controls in a new cohort recruited in 2022 was plotted by weight, rather than age, the difference between cases and controls for both sexes disappeared. Reanalyzing data from the original 2013 cohort, we found that differences in weight accounted for grip strength differences between cases and controls in girls and young women, but not in boys and young men. Finally, we tested whether a GALT-null rat model of CG also showed a grip strength deficit-it did-and again the difference between GALT-null and wild-type rats associated with differences in body mass. Combined, these results confirm that GALT deficiency is associated with a grip strength deficit in both young patients with CG/CVG and GALT-null rats, and further demonstrate that this phenotype may be secondary to growth delay, and therefore not evidence of a muscle abnormality.

Hand fine motor control in classic galactosemia.

Classic galactosemia (CG) is a rare inborn error of metabolism that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad range of complications that can include motor difficulties. The goal of this study was to characterize hand fine motor control deficit among children and adults with classic galactosemia (CG). Specifically, we used Neuroglyphics software to collect digital Archimedes spiral drawings on a touch screen from 57 volunteers with CG (cases) and 80 controls. Hand fine motor control was scored as root mean square (RMS) of spirals drawn relative to an idealized template. Presence of tremor was defined as a peak in periodicity of changes in drawing speed or direction in the 4-8 Hz range. We observed a highly significant difference (P < .001) in RMS scores between cases and controls, with almost 51% of cases showing at least 1 of 4 spirals scoring outside the 95th percentile for controls. The corresponding prevalence for controls was 10%. Similarly, more than 35% of cases, and almost 14% of controls, showed at least 1 of 4 spirals with a tremor amplitude above the 95th % cutoff for controls. Our results both confirm and extend what is known about hand fine motor control deficit among children and adults with CG and establish digital assessment as a useful approach to quantify this outcome.

Developmental Changes in Tongue Strength, Swallow Pressures, and Tongue Endurance.

Maximum tongue strength, mean swallow pressures, and tongue endurance were measured in 324 children ages 6-12 years. The purpose of this study was to measure saliva swallow pressures in absolute terms (i.e., kilopascals) and as a percentage of maximum tongue strength to determine functional reserve in across ages in children and to examine factors that may influence tongue strength and swallow pressures including age, tongue endurance, and tongue-tie. The study results showed that maximum tongue strength and swallow pressures increased with age, while tongue endurance did not. Swallow pressures averaged 44% of maximum tongue strength across ages, indicating that children typically have a functional reserve of 56%. Tongue strength and swallow pressures were not decreased in the 20 children with tongue-tie. A sample clinical case is discussed.

International clinical guideline for the management of classical galactosemia: diagnosis, treatment, and follow-up.

Classical galactosemia (CG) is an inborn error of galactose metabolism. Evidence-based guidelines for the treatment and follow-up of CG are currently lacking, and treatment and follow-up have been demonstrated to vary worldwide. To provide patients around the world the same state-of-the-art in care, members of The Galactosemia Network (GalNet) developed an evidence-based and internationally applicable guideline for the diagnosis, treatment, and follow-up of CG. The guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. A systematic review of the literature was performed, after key questions were formulated during an initial GalNet meeting. The first author and one of the working group experts conducted data-extraction. All experts were involved in data-extraction. Quality of the body of evidence was evaluated and recommendations were formulated. Whenever possible recommendations were evidence-based, if not they were based on expert opinion. Consensus was reached by multiple conference calls, consensus rounds via e-mail and a final consensus meeting. Recommendations addressing diagnosis, dietary treatment, biochemical monitoring, and follow-up of clinical complications were formulated. For all recommendations but one, full consensus was reached. A 93 % consensus was reached on the recommendation addressing age at start of bone density screening. During the development of this guideline, gaps of knowledge were identified in most fields of interest, foremost in the fields of treatment and follow-up.

Facial and Lingual Strength and Endurance in Skilled Trumpet Players.

UNLABELLED: Trumpet players produce and manipulate sound through their instrument by articulating the lips, cheeks, and tongue to create a proper airflow. These sustained muscle contractions may result in increased facial and lingual strength and endurance. The purpose of this study was to determine if adult trumpet players who practice at least 6 hrs/wk differed from adult non-trumpet-playing controls in strength and endurance of the lips, cheeks, and tongue. METHODS: This case-control study involved 16 trumpet players, 16 healthy controls balanced for age and sex, and 1 trumpet player 25 years post-Bell's palsy. Strength and endurance of lip, cheek, and tongue muscles were measured using the Iowa Oral Performance Instrument (IOPI Medical, Redmond, WA). Maximum strength was the greatest pressure value of three encouraged trials. Endurance was the length of time the participant was able to sustain 50% of maximum strength. RESULTS: The findings indicate that trumpet players had greater facial strength and endurance, which was objectively quantified using commercially available equipment. The trumpet players had greater cheek strength and greater lip endurance than controls. Tongue strength and endurance did not differ between the trumpet players and controls. Tongue strength was negatively associated with age, which is consistent with previous studies. The trumpet player with a history of Bell's palsy had decreased cheek strength and endurance on his affected side compared to his unaffected side, although this difference was comparable to the differences between right and left cheek strength in trumpet players without a history of facial nerve damage.

Virtual Post-Intervention Speech and Language Assessment of Toddler and Preschool Participants in Babble Boot Camp.

PURPOSE: Babble Boot Camp (BBC) is a parent-implemented telepractice intervention for infants at risk for speech and language disorders. BBC uses a teach-model-coach-review approach, delivered through weekly 15-min virtual meetings with a speech-language pathologist. We discuss accommodations needed for successful virtual follow-up test administration and preliminary assessment outcomes for children with classic galactosemia (CG) and controls at age 2.5 years. METHOD: This clinical trial included 54 participants, 16 children with CG receiving BBC speech-language intervention from infancy, age 2 years, five children receiving sensorimotor intervention from infancy and changing to speech-language intervention at 15 months until 2 years of age, seven controls with CG, and 26 typically developing controls. The participants' language and articulation were assessed via telehealth at age 2.5 years. RESULTS: The Preschool Language Scale-Fifth Edition (PLS-5) was successfully administered with specific parent instruction and manipulatives assembled from the child's home. The GFTA-3 was successfully administered to all but three children who did not complete this assessment due to limited expressive vocabularies. Referrals for continued speech therapy based on PLS-5 and GFTA-3 scores were made for 16% of children who received BBC intervention from infancy as compared to 40% and 57% of children who began BBC at 15 months of age or did not receive BBC intervention, respectively. CONCLUSIONS: With extended time and accommodations from the standardized administration guidelines, virtual assessment of speech and language was possible. However, given the inherent challenges of testing very young children virtually, in-person assessment is recommended, when possible, for outcome measurements.

The adult galactosemic phenotype.

BACKGROUND: Classic galactosemia is an autosomal recessive disorder due to galactose-1-phosphate uridyltransferase (GALT) deficiency. Newborn screening and early treatment do not completely prevent tremor, speech deficits, and diminished IQ in both sexes and premature ovarian insufficiency (POI) in women. Data on how individuals with galactosemia fare as adults will improve our ability to predict disease progression. METHODS: Thirty-three adults (mean age = 32.6 ± 11.7 years; range = 18-59) with classic galactosemia, confirmed by genotype and undetectable GALT enzyme activity, were evaluated. Analyses assessed associations among age, genotype, clinical features and laboratory measures. RESULTS: The sample included 17 men and 16 women. Subjects exhibited cataracts (21%), low bone density (24%), tremor (46%), ataxia (15%), dysarthria (24%), and apraxia of speech (9%). Subjects reported depression (39%) and anxiety (67%). Mean full scale IQ was 88 ± 20, (range = 55-122). All subjects followed a dairy-free diet and 75-80% reported low intake of calcium and vitamin D. Mean height, weight and body mass were within established norms. All female subjects had been diagnosed with POI. One woman and two men had had children. Logistic regression analyses revealed no associations between age, genotype or gender with IQ, tremor, ataxia, dysarthria, apraxia of speech or anxiety. Each 10- year increment of age was associated with a twofold increase in odds of depression. CONCLUSIONS: Taken together, these data do not support the hypothesis that galactosemia is a progressive neurodegenerative disease. However, greater attention to depression, anxiety, and social relationships may relieve the impact of this disorder in adults.

Appetite-guided approach to pediatric enteral tube weaning in the home setting: A pilot study.

BACKGROUND: Infants and children, who temporarily use feeding tubes to maintain body composition and growth, often have difficulty resuming oral feeds once medically stable. We report survey results from Growing Independent Eaters (GIE), an interdisciplinary approach providing home-based virtual support during a child-led appetite-guided enteral wean. METHOD: Surveys addressing participant wean success, weight, and feeding practices were sent to 76 families who participated in a GIE-led wean; 31 surveys were completed and returned. RESULTS: All participants who were not eating or drinking orally prewean were fully or partially weaned off enteral support. Infants weaned faster (37.7 days) than children (80.1 days). Mean weight loss during the intervention was 6.6% for infants and 5.9% for children. Six months postwean, 93% of participants surpassed their prewean weight. CONCLUSION: The GIE method was successful for weaning infants and children off enteral support.

Acute and early developmental outcomes of children with Duarte galactosemia.

A recent study demonstrated that children with Duarte galactosemia (DG) do not show increased prevalence of detectable developmental complications when 6-12 years old. However, that study left unanswered whether infants with DG might be at increased risk for acute problems when drinking milk or whether children with DG younger than 6 years might show increased prevalence of perhaps transient developmental challenges. Here, we have addressed both of these questions by analyzing parent/guardian-reported data collected retrospectively for 350 children, 206 with DG and 144 unaffected siblings from the same families. The variables analyzed included whether each child had experienced (1) acute complications in infancy, (2) early intervention services when <3 years old, and/or (3) special educational services when 3-5 years old. For each case-control comparison, or case-by-diet comparison, we used logistic regression that included the following potential covariates: age, sex, race, family income, and parent education, as appropriate. We found that none of the three outcome variables tested showed significant differences between cases and controls, or among cases as a function of galactose exposure in infancy. To the limits of our study, we therefore conclude that regardless of whether a child with DG drinks milk or low-galactose formula as an infant, they are not at increased risk for acute complications or early childhood developmental challenges that require intervention.

Voice disorders in children with classic galactosemia.

Children with classic galactosemia are at risk for motor speech disorders resulting from disruptions in motor planning and programming (childhood apraxia of speech or CAS) or motor execution (dysarthria). In the present study of 33 children with classic galactosemia, 21% were diagnosed with CAS, 3% with ataxic dysarthria, and 3% with mixed CAS-dysarthria. Voice disorders due to laryngeal insufficiency were common in children with dysarthria and co-occurred with CAS. Most (58%) of the children with classic galactosemia had decreased respiratory-phonatory support for speech, and 33% had disturbed vocal quality that was indicative of cerebellar dysfunction. Three children, two diagnosed with CAS and one not diagnosed with a motor speech disorder, had vocal tremors. Treatment of voice dysfunction in neurogenic speech disorders is discussed.

The use of simulation in training graduate students to perform transnasal endoscopy.

A challenge facing the field of speech-language pathology is how to equip students at the university level with the transnasal endoscopy skills needed to perform fiberoptic endoscopic evaluation of swallowing (FEES). The use of simulation has the potential to allow students to gain transnasal endoscopy experience with repetitive practice without compromising patients. The present study examined the effects of two different forms of simulation training on multiple transnasal endoscopic passes on healthy volunteers by graduate student clinicians as measured by procedure duration and confidence ratings. Eighteen speech-language pathology graduate student clinicians were randomly assigned to groups that utilized either a human patient simulator (HPS) or a non-lifelike simulator for transnasal endoscopy training. Using a flexible nasal endoscope, each clinician performed seven training passes on a simulator and one pass on two different volunteers. Each volunteer was endoscoped two times, once by a clinician trained using a HPS and once by a clinician trained using a non-lifelike simulator. There was no difference in pass times on volunteers between clinicians trained using the HPS and clinicians trained on the non-lifelike simulator. Both training groups were faster and more confident on the second endoscopy on a volunteer than on the first.

Extensions to the Speech Disorders Classification System (SDCS).

This report describes three extensions to a classification system for paediatric speech sound disorders termed the Speech Disorders Classification System (SDCS). Part I describes a classification extension to the SDCS to differentiate motor speech disorders from speech delay and to differentiate among three sub-types of motor speech disorders. Part II describes the Madison Speech Assessment Protocol (MSAP), an ∼ 2-hour battery of 25 measures that includes 15 speech tests and tasks. Part III describes the Competence, Precision, and Stability Analytics (CPSA) framework, a current set of ∼ 90 perceptual- and acoustic-based indices of speech, prosody, and voice used to quantify and classify sub-types of Speech Sound Disorders (SSD). A companion paper provides reliability estimates for the perceptual and acoustic data reduction methods used in the SDCS. The agreement estimates in the companion paper support the reliability of SDCS methods and illustrate the complementary roles of perceptual and acoustic methods in diagnostic analyses of SSD of unknown origin. Examples of research using the extensions to the SDCS described in the present report include diagnostic findings for a sample of youth with motor speech disorders associated with galactosemia, and a test of the hypothesis of apraxia of speech in a group of children with autism spectrum disorders. All SDCS methods and reference databases running in the PEPPER (Programs to Examine Phonetic and Phonologic Evaluation Records) environment will be disseminated without cost when complete.

Perceptual and acoustic reliability estimates for the Speech Disorders Classification System (SDCS).

A companion paper describes three extensions to a classification system for paediatric speech sound disorders termed the Speech Disorders Classification System (SDCS). The SDCS uses perceptual and acoustic data reduction methods to obtain information on a speaker's speech, prosody, and voice. The present paper provides reliability estimates for the two perceptual methods (narrow phonetic transcription; prosody-voice coding) and the acoustic analysis methods the SDCS uses to describe and classify a speaker's speech competence, precision, and stability. Speech samples from 10 speakers, five with significant motor speech disorder and five with typical speech, were re-measured to estimate intra-judge and inter-judge agreement for the perceptual and acoustic methods. Each of the speakers completed five speech tasks (total = 50 datasets), ranging in articulatory difficulty for the speakers, with consequences for the difficulty level of data reduction. Point-to-point percentage of agreement findings for the two perceptual methods were as high or higher than reported in literature reviews and from previous studies conducted within the laboratory. Percentage of agreement findings for the acoustics tasks of segmenting phonemes, editing fundamental frequency tracks, and estimating formants ranged from values in the mid 70% to 100%, with most estimates in the mid 80% to mid 90% range. Findings are interpreted as support for the perceptual and acoustic methods used in the SDCS to describe and classify speakers with speech sound disorders.

Maximal tongue strength in typically developing children and adolescents.

Evaluating tongue function is clinically important as the generation of adequate pressure by the anterior tongue against the hard palate is crucial for efficient oropharyngeal swallowing. Research in the evaluation of tongue function in pediatric populations is limited due to questions about the reliability of children's performance on objective measures of tongue strength and the lack of comparative data from typically developing children. The present study examined tongue strength in 150 children and adolescents, 3-16 years of age, with no history of speech or swallowing disorders using the Iowa Oral Pressure Instrument (IOPI). Children as young as 3 years of age were able to tolerate the IOPI standard tongue bulb and were reliable performers on measures of tongue strength with an unconstrained mandible. Tongue strength measurements were elicited in blocks of three trials with a 30-s rest between the trials and a 20-min rest between blocks. Tongue strength increased with age with no consistent best trial across ages and participants. Males showed a slight increase in tongue strength over females at ages 14 and 16. This study suggests maximum pediatric tongue strength may be reliably evaluated using commercially available equipment and provides a limited sample comparative database.

Oral and manual force control in preschool-aged children: is there evidence for common control?

The authors examined and compared the development of oral and manual force control in preschool-aged children. In all, 50 typically developing children (aged 3-5 years) performed maximal strength tasks and submaximal visually guided tasks using tongue elevation, power, and precision grips. Dependent measures included strength, rate of force rise, initial force overshoot, force variability, and rate of force release. The authors performed age- and performance-related analyses. Results revealed similar changes for tongue, fingers, and hands across age- and performance-related measures for strength, initial force overshoot, and rate of force release. There were no significant changes in rate of force rise with increasing age. Force variability measures showed effector-specific changes with decreases across age- and performance-related measures for the hands and fingers but not for the tongue. Changes common across effector systems likely reflect biological development coupled with cognitive-strategic development. Effector-specific changes in force variability likely reflect experience gained through functional tasks influencing biological and cognitive-strategic development. Lack of change in force variability of the tongue suggests that fine control of the tongue is activity specific; thus, nonfunctional tasks are not likely to be sensitive to experience-related biological development.

Tongue Strength in Children With and Without Speech Sound Disorders.

Purpose The purpose of this cross-sectional investigation was to expand the comparative database of pediatric tongue strength for children and adolescents with typical development, ages 3-17 years, and compare tongue strength among children with typical development, speech sound delay/disorders (SD), and motor speech disorders (MSDs). Method Tongue strength was measured using the Iowa Oral Performance Instrument in a total of 286 children and adolescents, 228 with typical development, 16 with SD, and 42 with MSDs, including classic galactosemia, a known risk factor for MSD ( n = 33) and idiopathic MSD ( n = 9). Results For all groups, tongue strength increased rapidly from 3 to 6.5 years of age and then continued to increase with age at a slower rate until 17 years of age. Children with SD's tongue strength did not differ from their typically developing (TD) peers. Children and adolescents with MSDs had decreased tongue strength compared to children with typical development or SD. Tongue strength was not related to severity of speech sound disorders in SD or MSD. Conclusion Weak tongue strength does not appear to contribute to speech errors in children with speech sound delays but does appear to be related to speech sound disorders that are neurologic in origin (developmental MSD).

Developmental Outcomes in Duarte Galactosemia.

: media-1vid110.1542/5849572227001PEDS-VA_2018-2516Video Abstract OBJECTIVES: For decades, infants with Duarte galactosemia (DG) have been identified by newborn screening (NBS), but whether they should be treated with dietary restrictions of galactose has remained unknown. To clarify, we conducted a study of dietary and developmental outcomes in 206 children with DG (case patients) and 144 controls, all of whom were 6 to 12 years old. METHODS: We recruited case patients from states where they were identified by NBS; unaffected siblings served as controls. Diet in infancy was ascertained by retrospective parent surveys; developmental outcomes were assessed in 5 domains, yielding 73 outcome measures for each child. We divided subjects randomly into independent discovery (n = 87) and validation (n = 263) sets. We tested the discovery set to order the 73 outcome measures by ascending P values and tested the 10 outcomes with the lowest P values for possible association with DG in the validation set. We also tested these same 10 outcomes for possible association with milk exposure in infancy among case patients in the validation set. RESULTS: None of the 73 outcomes tested in the discovery set revealed significant association with DG, and none of the 10 outcomes tested in the validation set revealed either significant association with DG or significant association with milk exposure among children with DG. CONCLUSIONS: Through our results, we demonstrated that there were no significant differences in outcomes tested between case patients and controls or among case patients as a function of milk exposure in infancy. In this study, we provide a long-needed foundation of knowledge for health care providers, families, and NBS professionals seeking to make evidence-based decisions about DG.