Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebrospinal fluid aminoacid analysis in a girl with severe psychomotor retardation, hypotonia, hyperreflexia and growth acceleration showed highly increased levels of free gamma-aminobutyric acid (4.8 mumol/l; range in twenty controls 0.04-0.12, median 0.08), homocarnosine, a dipeptide of gamma-aminobutyric acid and histidine (23.4 mumol/l; control range 4.0-8.7, median 7.6) and of beta-alanine, an alternative substrate for gamma-aminobutyric acid-transaminase (0.48 mumol/l; control range 0.02-0.06, median 0.05). Liver gamma-aminobutyric acid-transaminase activity was deficient (0.07 mumol/mg protein h; range in ten controls 0.31-0.69, median 0.38). Fasting plasma growth hormone levels were increased (7.9-38.4 ng/ml; nl less than 5). Brain evoked responses were suggestive of leukodystrophy. A brother of this patient, showing a similar clinical picture, had died at one year. Postmortem examination of his brain showed leukodystrophy of the type seen in amino acidopathies such as phenylketonuria. This appears to be the first report of gamma-aminobutyric acid-transaminase deficiency.
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PMID:Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. 614 8

Forty patients with the Prader-Willi syndrome have been examined. The typical features begin in gestational life with poor fetal vigor and difficulties with birth and post-partum feeding. The classical features of hypotonia, small hands and feet, cryptorchidism can be identified at this time. The delayed milestones, mental retardation and obesity become more prominent later. The average height of the patients in this series who were admitted to the Clinical Study Center was 149 cm and their weight was 114 kg. The weight and height curves show that Prader-Willi individuals are consistently shorter and heavier than normal children. Tests of endocrine function showed normal glucose tolerance. Insulin secretion was increased in relation to obesity. The rise in growth hormone (hGH) after injecting insulin to induce hypoglycemia and after the infusion of arginine was comparable to other obese individuals but was low in comparison to normal weight subjects. There was no rise in growth hormone with L-dopa administration, but there was a rise in hGH with the administration of 2-deoxy-D-glucose. The hypoglycemia produced by insulin was greater in the Prader-Willi patient than in obese controls. The rise in TRH (thyrotropin-releasing hormone) following the injection of TSH (thyrotropin stimulating hormone) was greater in the Prader-Willi patients than in the obese controls. Hypogonadism was routine in this series, and the response to LRH (luteinizing releasing hormone) was absent in all tested subjects. Treatment with clomiphene for 30 to 90 days significantly increased the response to LRH in three adult individuals who had not been treated with gonadal steroids previously and who were hypogonadal. Rectal temperature declined in three of the five Prader-Willi patients during exposure to an ambient temperature of 4 degrees C, but none of the three obese controls showed a decline. Food intake averaged 5167 kcal/d when six patients were given trays containing more food than they could eat. Food intake was not reduced when tryptophan was added to the diet. Salivary secretion was reduced in the Prader-Willi patients. A number of pulmonary function tests were significantly reduced in the study patients compared to obese or normal weight controls. The anatomic findings in four autopsied patients with the Prader-Willi syndrome showed no significant differences from those of obese subjects without this syndrome. The chromosomal pattern showed a deletion or translocation at chromosome 15 in 3 of 12 patients in whom this test was performed. These findings in 40 patients with the Prader-Willi syndrome have been compared with the information contained in 159 reports published in the medical literature.
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PMID:The Prader-Willi syndrome: a study of 40 patients and a review of the literature. 633 43

The syndrome of septo-optic dysplasia with congenital hypopituitarism consists of optic nerve hypoplasia, midline malformations of the prosencephalon and hypothalamic hypopituitarism. There is great variability of these features and clinical manifestation is age-dependent: Newborns present with hypoglycemic seizures, apnea, cyanosis, hypotonia, prolonged jaundice (and micropenis in boys) because of growth hormone and/or ACTH-deficiencies. Wandering eye movements and more or less visual disturbance become evident during infancy and growth retardation even later in some cases. Early recognition is facilitated by the pathognomonic fundoscopic findings, together with normal electroretinogram, absent visually evoked potentials and computer tomography. Early hormone substitution is essential to prevent hypoglycemic damage.
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PMID:[Septo-optic dysplasia with congenital hypopituitarism (author's transl)]. 719 68

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.
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PMID:MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings. 859 94

The 18q- syndrome is one of the commonest deletion syndromes. Clinical characteristics are variable but may include: hypotonia, tapered digits, "carp-like" mouth, mental retardation, and hearing impairment. Growth failure (GF; both weight and height < 3%) was reported in 80% of affected individuals. We evaluated growth hormone (GH) sufficiency in 5 18q- syndrome patients, 3 of whom had growth failure (< 3% weight and height); the remaining 2 had normal growth parameters. Laboratory evaluation of growth included measurement of IGF-1, IGFBP-3, bone ages and GH response to pituitary provocative agents. Three patients failed to produced adequate GH following stimulation testing. Of 3 patients with inadequate GH production, 1 had normal growth (above 3%). Only 1 of 5 patients had normal GH production and normal growth parameters. Our findings to date suggest that GH deficiency is common in individuals with the 18q- syndrome. The pathogenesis of this finding is unknown. We postulate that a gene(s) on 18q is involved in GH production.
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PMID:Growth hormone deficiency associated in the 18q deletion syndrome. 906 76

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.
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PMID:[General anesthesia in Prader-Willi syndrome]. 910 80

Prader-Labhart-Willi syndrome (PWS)-characterized by severe obesity, short stature, hypogonadism, and muscle hypotonia-appears to be an interesting model for body-composition abnormalities. Twenty-seven PWS patients (15 males and 12 females) aged 6-22 y underwent total-body analysis by dual-energy X-ray photon absorptiometry (DXA). For each PWS patient two age- and sex-matched control subjects were studied: one obese subject with a relative body weight (RBW > 120%) and body mass index (BMI) similar to that of the patient and one normal-weight subject (RBW < 120%). Percentage body fat was significantly greater in PWS patients than in obese subjects (47.4 +/- 7.2% compared with 41.9 +/- 9.9%, P < 0.0001) and the same difference was evident for arms and legs but not for the trunk. Lean mass was significantly lower in PWS patients (26.4 +/- 8.2 kg) than in normal-weight subjects (32.9 +/- 10.2 kg) and even more so than in obese subjects (40.3 +/- 13.2 kg) (P < 0.0001). The most affected regions were limbs; thus, the ratio of lean mass in the trunk to that in the limbs was significantly higher in PWS patients (1.19 +/- 0.15) than in obese (1.07 +/- 0.13) and normal-weight (1.07 +/- 0.09) subjects (P < 0.002). The ratio of fat mass to lean mass was significantly higher in PWS patients than in obese subjects (0.90 +/- 0.32 and 0.74 +/- 0.27, P < 0.05). Bone mineral content (BMC) was significantly lower in PWS patients (1503 +/- 46 g) than in normal-weight (1876 +/- 677 g) and obese (2322 +/- 773 g) subjects (P < 0.0001); this difference was most pronounced in the limb region. Bone mineral density (BMD) in PWS patients (0.993 +/- 0.116 g/cm2) did not differ significantly from that of normal-weight subjects (1.033 +/- 0.147 g/cm2) but was significantly lower than that of obese subjects (1.154 +/- 0.139 g/cm2). The influence of age on body composition was assessed by comparing two age subgroups (< 12 y, n = 10; and > or = 12 y, n = 17). The older PWS patients had higher adiposity, lower BMC, and dramatically lower BMD. Also, the lean mass deficit increased with age so that the ratio of fat mass to lean mass was close to 1. In conclusion, PWS patients showed a peculiar body composition, to some extent similar to that found in subjects deficient in growth hormone or even to sedentary and elderly people. These results suggest the importance of an accurate analysis of body composition in PWS patients.
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PMID:Peculiar body composition in patients with Prader-Labhart-Willi syndrome. 935 52

We report on a patient with Nevo syndrome manifesting intrauterine and postpartum overgrowth, accelerated osseous maturation, dolichocephaly, highly arched palate, large, low-set ears, cryptorchidism, delayed neuropsychological development, hypotonia, adema, contractures of the hands and feet, a single a transverse palmar crease, and tapering digits. After meningococcal sepsis at age 6 months, he remained decerebrate. Thereafter, overgrowth and especially weight gain were extremely accelerated until his death at age 18 months, at which time his height was 103 cm and his weight was 23 kg. In addition to low plasma concentrations of growth hormone and insulin-like growth factor, severe insulin resistance was observed. It is presumed that a selective defect in insulin-stimulated glucose uptake, with preservation of anabolic effect, was one of the causes of his "overgrowth without growth hormone," at least in the last 12 months of life after severe brain damage.
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PMID:Nevo syndrome. 950 68

Over the last 3 years we ascertained 42 patients for statural overgrowth and/or macrocephaly, who also had mild developmental delay. There were 39 males and three females, two of whom were sisters. In no case was tall stature a familial characteristic. Family history was unremarkable, except for the case of the two sisters. Physical examination did not demonstrate any consistent pattern of malformations or anomalies identifying a syndrome, known or unknown. Chromosomes were apparently normal and the molecular test for the fragile X syndrome yielded normal results in all cases. Muscular hypotonia, advanced bone age, and epilepsy were relatively consistent manifestations. The hypothalamus-pituitary axis seemed to be intact when tested through the blood levels of insulin-like growth factors I and II and of the insulin-like growth binding protein 3, and the excess of growth was apparently growth hormone independent. The condition comprising excessive growth, developmental delay, muscular hypotonia, absence of a consistent pattern of physical anomalies, and apparently sporadic occurrence, largely limited to males, may be heterogenous.
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PMID:Nonsyndromal overgrowth in males with mild psychomotor delay. 978 10

Recently a type of growth failure (Hyperphagic Short Stature) has been described, in which there is potentially reversible severe impairment of growth hormone secretion, in association with excessively high levels of psychosocial stress. This condition is a variant of the disorder formerly known as Psychosocial Dwarfism. In the present study we compared children with Hyperphagic Short Stature (N = 25, aged 9.04 years+/-3.78, 72% male) and a closely matched sample with normal height, drawn from comparably stressful family circumstances (N = 25, aged 10.61+/-3.04, 60% male). Measures of the psychosocial environment, anthropometry, and developmental history from infancy were obtained. Many symptoms thought previously to be characteristics of psychosocial dwarfism were found to be nonspecific stress responses. Hypotonia (p < .05), enuresis/encopresis (p < .01), and sleep cycle disruption (p < .05) did differentiate the groups. Growth, appetite, and sleep are all influenced by hypothalamic nuclei, suggesting hypothalamic pathology could account for most of the clinical features of Hyperphagic Short Stature.
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PMID:A case-comparison study of the characteristics of children with a short stature syndrome induced by stress (Hyperphagic Short Stature) and a consecutive series of unaffected "stressed" children. 1050 91


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