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Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was, Patients with classical galactosemia frequently suffer from complications affecting the brain for which prognostic factors are lacking. In our cohort of classical galactosemia patients, we demonstrated a highly variable outcome, distinguished a subgroup of milder ‘variant patients’ and found an association between MRI abnormalities and lower intellectual outcomes and movement disorders., Graphical Abstract Graphical Abstract

Mice produce ultrasonic vocalizations (USVs) in a variety of social situations, and USVs have been leveraged to study many neurological diseases including verbal dyspraxia, depression, autism and stuttering. Pups produce isolation calls, a common USV, spontaneously when they are isolated from their mother during the first 2 weeks of life. Several genetic manipulations affect (and often reduce) pup isolation calls in mice. To facilitate the use of this assay as a means of testing whether significant functional differences in genotypes exist instead of contextual differences, we test the variability inherent in many commons measures of mouse vocalizations. Here we use biological consistency as a way of determining which are reproducible in mouse pup vocalizations. We present a comprehensive analysis of the normal variability of these vocalizations in groups of mice, individual mice and different strains of mice. To control for maturation effects, we recorded pup isolation calls in the same group of C57BL/6J 5 days old mice twice, with 1 h of rest in between recordings. In almost all cases, the group averages between the first and second recordings were the same. We also found that there were high correlations in some parameters in individual mice across recording while others were not well correlated. These findings could be replicated for the majority of features in a separate group of C57BL/6J mice and a group of 129/SvEvBrd-C57BL/6J mice. The averages of these mouse USV features are highly consistent and represent a robust assay to test the effects of genetic and other interventions in the experimental setting.

In spite of adequate dietary regimen, many patients with galactosemia have developmental abnormalities. We studied 8 patients with galactosemia, aged 9 months to 19 years who had all been treated with a galactose-free diet from an early stage. Neurological functioning, general developmental, and language and speech development were assessed in all cases. The results show that even medically well treated children and young adults with galactosemia are at risk to develop disabilities, including mental retardation, speech and language disabilities. Verbal dyspraxia was diagnosed in 3 of 6 patients, who had acquired verbal language, all with IQ 70 or below. This may indicate that verbal dyspraxia is just one symptom among others in patients with galactosemia and mental retardation.

This paper discusses the relationship between the dysarthrias and verbal dyspraxia in adults and children, and examines these conditions with reference to current theories and a model. The empirical basis for the study described here was the examination in depth of the speech of six subjects, each of whom presented with neurological disorders of different origins: two adults, chosen to exemplify the acquired conditions of dysarthria and dyspraxia, and four children. The speech analyses used profiling techniques of segmental phonological and prosodic assessment, and electropalatographic (EPG) examination, and the profiles thus obtained were compared between subjects and across client groups. The hypothesis was that in-depth analyses would provide distinguishing characteristics between the two neurological conditions, such that the children with suspected developmental verbal dyspraxia would demonstrate differences from those with developmental dysarthria, and clear similarities to the dyspraxic adult. The ...

This paper discusses the relationship between the dysarthrias and verbal dyspraxia in school-aged children. Using perceptual profiling and instrumental (electropalatographic) techniques, the speech of a small subject group was analysed in depth, in order to compare the two neurological conditions. The aim of the study was to provide distinguishing characteristics between the conditions. The rationale for the conclusion from the study is examined in relation to clinical implications.

Speech/language disorders are common in the fragile X syndrome. [Howard-Peebles, 1979: Am J Hom Genet 31:214-222; Renier et al., 1983: J Ment Defic Res 27:51-59; Sparks, 1984: Birth Defects and Speech-Language Disorders, pp. 39-43; Hanson et al., 1986: Am J Med Genet 23:195-206]. Verbal paraphasias have been considered a rare feature and word-finding difficulties have seldom been reported. Here we report on ten Brazilian patients who were evaluated for speech/language disturbances and found that word-finding difficulties were present in 50% of the cases, which is a slightly higher frequency than that of clear dyspraxia. We suggest, therefore, that word-finding difficulties and verbal dyspraxia can be a common feature within the spectrum of this syndrome. Additional speech findings are discussed.

The relationship between oral-stereognosis (O.S.) and the nature and severity of verbal dyspraxia was investigated in 16 post-C.V.A. dyspraxic patients. Scores for oral stereognosis were correlated with — (1) repetition of sounds and sentences in the Mayo Clinic Test of Verbal Dyspraxia (Darley, 1975); (2) words and phrases from Speech and Language Disturbances subtest of the Minnesota Test of Differential Diagnosis and Aphasia. In addition, subjects were assigned to one of four groups depending upon their presenting verbal symptoms, i.e., substitution; substitution and perseveration; substitution and initiation; and substitution, perseveration and initiation. Results indicated that O.S. scores correlated highly with the sounds and phrases subtests as well as with errors of substitution providing that the subject did not exhibit difficulties on initiation. Results were discussed in terms of the possible locus of brain lesion. Low scores on the O.S. test may indicate lesions to the post central kinesthetic...

It is our clinical experience that in a number of aphasics, a distinctive articulatory disorder is found in the absence of the observable paralysis or paresis of the speech musculature. The term “motor aphasia” or “Broca's aphasia” has generally been applied to designate this type of disorder.The studies in recent years, however, have disclosed that this kind of disorder, a disorder of programming and executing articulatory movements (verbal apraxia or apraxia of speech), can be distinguished from the disorder of symbolic processes, i. e. aphasia.In this paper, the characteristics of verbal apraxia were described as well as the methods of testing oral and verbal apraxias. The therapy methods of verbal apraxia were reviewed with a special emphasis on the works done by Luria, et al..It was suggested that verbal apraxia, though a clearly definable clinical entity, might not be a homogeneous disorder. More comprehensive investigation of the nature of this disorder will be necessary before we can set up more systematic therapeutic procedures.

The instrumental techniques of electropalatography and pneumotachography are used to examine details of tongue-palate contacts and VOT characteristics of three adult male subjects: two described as dysarthric and one as dyspraxic. A comparison is made between the subjects, and the results are compared with data from four normal speakers. The information is considered with reference to the neurological bases of these disorders of speech, and the advantages of an instrumental investigation over traditional auditory based assessments are exemplified. Some implications for therapy are also considered.

In 1861 Paul Broca described his patient “Tan” as having lost “the memory for the procedure one has to follow in order to articulate words”. This condition he called aphemia but subsequently it became known as Broca’s aphasia. Broca described a disorder in which the patient could understand spoken language, ideas were intact and he could recognize words and phrases which he could not pronounce nor repeat. Subsequent autopsy of Tan’s brain revealed a lesion in the area of the third convolution of the frontal left lobe (later designated Broca’s area). The features of this disorder parallel some of those associated with what later on became known as dyspraxia of speech or verbal dyspraxia. By annexing the word aphasia to Broca’s name a linguistic as against motoric connotation was apparent and this sparked off a volley of controversy which has been maintained with fervour ever since.