Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

The perception of complex harmonic patterns by profoundly hearing-impaired listeners.

In providing profoundly hearing-impaired persons with processed speech through a signal-processing hearing aid, it is important that the new speech code matches their auditory capacities. This processing capacity for auditory information was investigated in this study. In part 1, the subjects' ability to judge similarities among 8 different but related harmonic complexes was studied. The patterns contained different numbers of harmonics to a 125-Hz fundamental frequency; the harmonics had been spread over the spectrum in various ways. The perceptual judgments appeared to be based on a temporal cue, beat strength, and a spectral cue, related to the balance of high and low frequency components. In part 2, three sets of synthetic vowels were presented to the subjects. Each vowel was realized by summing harmonically related in-phase sinusoids at two formant frequencies. The sets differed in the number of sinusoids per formant: 1, 2 or 3. It was found that the subjects used spectral cues and vowel length for differentiating among the vowels. The overall results show the limited but perhaps usable ability of the profoundly impaired ear to handle spectral information. Implications of these results for the development of signal-processing hearing aids for the profoundly hearing impaired are discussed.

A model for context effects in speech recognition.

A model is presented that quantifies the effect of context on speech recognition. In this model, a speech stimulus is considered as a concatenation of a number of equivalent elements (e.g., phonemes constituting a word). The model employs probabilities that individual elements are recognized and chances that missed elements are guessed using contextual information. Predictions are given of the probability that the entire stimulus, or part of it, is reproduced correctly. The model can be applied to both speech recognition and visual recognition of printed text. It has been verified with data obtained with syllables of the consonant-vowel-consonant (CVC) type presented near the reception threshold in quiet and in noise, with the results of an experiment using orthographic presentation of incomplete CVC syllables and with results of word counts in a CVC lexicon. A remarkable outcome of the analysis is that the cues which occur only in spoken language (e.g., coarticulatory cues) seem to have a much greater influence on recognition performance when the stimuli are presented near the threshold in noise than when they are presented near the absolute threshold. Demonstrations are given of further predictions provided by the model: word recognition as a function of signal-to-noise ratio, closed-set word recognition, recognition of interrupted speech, and sentence recognition.