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)

Skeletal muscle hypotonia is a hallmark clinical finding in very-low-birth-weight (VLBW) human infants. Although the biochemical basis for this phenomenon is not completely understood, one hypothesis is that the phosphorylation potential is abnormally low in the skeletal muscle of these infants. Therefore, we used 31P-nuclear magnetic resonance (NMR) spectroscopy to measure phosphorus metabolites in the skeletal muscle of VLBW infants during rest and during reflex-induced muscle contractions. Compared with healthy larger infants or to adults, the total phosphorus NMR signal is lower in VLBW infants. In VLBW infants during rest, [PCr]/([PCr]+[Pi]), where PCr is phosphocreatine and brackets denote concentration, was 89% and [ATP]/[ADP][Pi] was 59% of that found in larger infants (P less than 0.05). During reflex-induced isometric contractions in VLBW infants, [PCr]/([PCr]+[Pi]) declined by 24% and [ATP]/[ADP][Pi] declined by 35% (P less than 0.05 vs. rest). In all conditions, muscle pH remained 7.1. Overall, the differences in skeletal muscle energy state during rest and the corresponding changes in concentration of high-energy phosphates during mild exercise suggest a very limited energy reserve in the hypotonic muscle of VLBW infants.
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PMID:Muscle phosphorus energy state in very-low-birth-weight infants: effect of exercise. 155 Feb 22

To address the role of high-energy phosphorus compounds in the hypotonia of vitamin D-dependent rickets, nuclear magnetic resonance spectra were obtained sequentially from resting gastrocnemius muscle of a 10-month-old infant with rachitic hypotonia during supplementation with vitamin D, calcium, and phosphorus. During the initial weeks of treatment, the hypotonia resolved before evidence of epiphyseal mineralization. Over the early treatment period, the muscle phosphocreatine/beta-adenosine triphosphate [PCr/beta-ATP] ratio increased from 2.7-2.8 [wk 1-2] to 3.9-4.5 [wk 7-9]. The PCr/beta-ATP ratio for 6-month-old normal infant gastrocnemius and adult forearm were 4.0 and 5.7, respectively. Muscle strength appeared to recover concomitantly with an increase in retained muscle phosphorus and high-energy phosphate compounds, and with relative increase in the muscle phosphocreatine to ATP ratio. The synchrony of clinical recovery may relate to the recovery kinetics of these metabolic changes.
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PMID:Hypotonia of rickets: a sequential study by P-31 magnetic resonance spectroscopy. 320 28

Clostridium botulinum can colonize and produce botulinal toxin in the human infant intestine, which the toxin then permeates to cause generalized flaccid paralysis, and occasionally, sudden death. This study was undertaken to test the hypothesis that toxins produced by other intestinal clostridia, e.g., C. difficile, might also cause systemic illness and sometimes death in infants (J Pediatr 100:568, 1982). Because this hypothesis could not be evaluated clinically until the systemic manifestations of C. difficile toxins in primates were known, infant rhesus monkeys were given 6 to 11 micrograms/kg of the recently purified C. difficile toxins A or B, either intravenously or intraperitoneally. The animals showed no abnormalities for several hours, but then developed lethargy, hypotonia, hypothermia, and, shortly before death, sudden elevation of serum concentrations of potassium, magnesium, and phosphorus and of enzymes that derived mainly from skeletal muscle, heart and brain. Five of six animals died quietly 3.5 to 8.0 hours after onset of symptoms. Death appeared to result from cessation of breathing, after which the sinus tachycardia then deteriorated to a flat ECG. Necropsy findings were insufficient to explain the cause of death. It appears that in infant monkeys microgram amounts of C. difficile toxins A and B can produce a rapid quiet death, the cause of which is undetectable at necropsy, a situation pathologically reminiscent of crib death in human infants, although the possible clinical identity of these two conditions has yet to be established.
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PMID:Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: physiologic and pathologic basis. 669 Jun 74

Phosphorus depletion in malnutrition has not generally received attention. Serum phosphorus was measured in healthy infants (1.8 mmol/L), in well-nourished infants with acute dehydrating gastroenteritis, and in infants suffering from malnutrition. Serum phosphorus levels were found to be low in well-nourished infants with acute dehydrating gastroenteritis (1.32 mmol/L) an exceptionally low in infants with kwashiorkor (1.10 mmol/L) especially when the latter condition was accompanied by severe diarrhoea (0.66 mmol/L). Hypophosphatemia, as well as hypokalemia, was associated with marked hypotonia. Low levels of serum phosphorus occurred in nine of the 10 malnourished children who died.
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PMID:Serum phosphorus in protein energy malnutrition. 682 Nov 15

Pyruvate dehydrogenase complex (PDHC) is an intramitochondrial multienzyme complex essential for the aerobic oxidation of glucose. The majority of patients with PDHC deficiency have abnormalities in the major catalytic and regulatory subunit, E1 alpha, which is encoded on the X chromosome. The clinical spectrum of PDHC deficiency is heterogeneous, particularly in heterozygous females, and diagnosis may be difficult. Three affected infant girls with PDHC deficiency were investigated. All had dysmorphic features, microcephaly with profound global developmental delay, and hypotonia. Systemic acidosis was absent, although serum lactate and pyruvate were abnormally elevated. Magnetic resonance imaging revealed hypoplasia of the corpus callosum in all patients. Proton magnetic resonance spectroscopy of brain revealed large increases in relative signal intensities for lactic acid and decreases in the relative signal intensities of N-acetylaspartate, a marker of neuronal damage or less. Phosphorus MRS of muscle revealed abnormally low phosphorylation potentials for all these patients, although the degree of abnormality was variable and not directly correlated with the amount of brain lactate. It is proposed that cerebral dysgenesis and cerebral lactic acidemia as shown by magnetic resonance imaging and proton magnetic resonance spectroscopy are useful diagnostic clues to PDHC deficiency, particularly in females in whom variable patterns of X-inactivation reduce sensitivity of laboratory diagnosis based on the biochemical studies of peripheral tissues. In addition, muscle bioenergetic abnormalities in conjunction with CNS dysfunction may contribute to profound hypotonia in this disorder.
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PMID:Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. 788 Mar 37

We describe an infant girl who presented at age 4 1/2 months with developmental delay, infantile spasms, hypotonia, and elevated lactate levels in the blood and cerebrospinal fluid. She had minor dysmorphic features. Muscle phosphorus magnetic resonance spectroscopy demonstrated reduced phosphocreatine and increased inorganic phosphate, suggesting a defect in oxidative energy metabolism. Pyruvate dehydrogenase activity in cultured fibroblasts was reduced (0.35 nmol/mg mitochondrial protein/min; controls 0.7-1.1 nmol/mg mitochondrial protein/min). Immunoblotting demonstrated a reduced amount of pyruvate dehydrogenase (PDH) E1 alpha immunoreactive protein with normal amounts of E2 protein. Single-strand conformational polymorphism analysis of E1 alpha cDNA prepared from fibroblasts disclosed an abnormal migration pattern, suggesting heterozygosity for a mutant allele. Dideoxy-fingerprinting of PCR-amplified genomic DNA was used to localize the mutation to exon 10. Direct sequencing demonstrated a novel 13-bp insertion mutation that would lead to premature termination of the protein product. This study further extends the allelic heterogeneity underlying PDH deficiency. The demonstration of bioenergetic abnormalities in muscle emphasizes that hypotonia in PDH deficiency may have combined peripheral and central etiologies. The results further suggest that the association of cerebral dysgenesis with lactic acidemia in females may be a useful clue to PDH deficiency.
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PMID:Association of cerebral dysgenesis and lactic acidemia with X-linked PDH E1 alpha subunit mutations in females. 877 Nov 69

It is widely appreciated that health food beverages are not appropriate for infants. Because of continued growth, children beyond infancy remain susceptible to nutritional disorders. We report on 2 cases of severe nutritional deficiency caused by consumption of health food beverages. In both cases, the parents were well-educated, appeared conscientious, and their children received regular medical care. Diagnoses were delayed by a low index of suspicion. In addition, nutritional deficiencies are uncommon in the United States and as a result, US physicians may be unfamiliar with their clinical features. Case 1, a 22-month-old male child, was admitted with severe kwashiorkor. He was breastfed until 13 months of age. Because of a history of chronic eczema and perceived milk intolerance, he was started on a rice beverage after weaning. On average, he consumed 1.5 L of this drink daily. Intake of solid foods was very poor. As this rice beverage, which was fallaciously referred to as rice milk, is extremely low in protein content, the resulting daily protein intake of 0.3 g/kg/day was only 25% of the recommended dietary allowance. In contrast, caloric intake was 72% of the recommended energy intake, so the dietary protein to energy ratio was very low. A photograph of the patient after admission illustrates the typical features of kwashiorkor: generalized edema, hyperpigmented and hypopigmented skin lesions, abdominal distention, irritability, and thin, sparse hair. Because of fluid retention, the weight was on the 10th percentile and he had a rotund sugar baby appearance. Laboratory evaluation was remarkable for a serum albumin of 1.0 g/dL (10 g/L), urea nitrogen <0.5 mg/dL (<0.2 mmol/L), and a normocytic anemia with marked anisocytosis. Evaluation for other causes of hypoalbuminemia was negative. Therapy for kwashiorkor was instituted, including gradual refeeding, initially via a nasogastric tube because of severe anorexia. Supplements of potassium, phosphorus, multivitamins, zinc, and folic acid were provided. The patient responded dramatically to refeeding with a rising serum albumin and total resolution of the edema within 3 weeks. At follow-up 1 year later he continued to do well on a regular diet supplemented with a milk-based pediatric nutritional supplement. The mortality of kwashiorkor remains high, because of complications such as infection (kwashiorkor impairs cellular immune defenses) and electrolyte imbalances with ongoing diarrhea. Children in industrialized countries have developed kwashiorkor resulting from the use of a nondairy creamer as a milk alternative, but we were unable to find previous reports of kwashiorkor caused by a health food milk alternative. We suspect that cases have been overlooked. Case 2, a 17-month-old black male, was diagnosed with rickets. He was full-term at birth and was breastfed until 10 months of age, when he was weaned to a soy health food beverage, which was not fortified with vitamin D or calcium. Intake of solid foods was good, but included no animal products. Total daily caloric intake was 114% of the recommended dietary allowance. Dietary vitamin D intake was essentially absent because of the lack of vitamin D-fortified milk. The patient lived in a sunny, warm climate, but because of parental career demands, he had limited sun exposure. His dark complexion further reduced ultraviolet light-induced endogenous skin synthesis of vitamin D. The patient grew and developed normally until after his 9-month check-up, when he had an almost complete growth arrest of both height and weight. The parents reported regression in gross motor milestones. On admission the patient was unable to crawl or roll over. He could maintain a sitting position precariously when so placed. Conversely, his language, fine motor-adaptive, and personal-social skills were well-preserved. Generalized hypotonia, weakness, and decreased muscle bulk were present. Clinical features of rickets present on examination included: frontal bossing, an obvious rachitic rosary (photographed), genu varus, flaring of the wrists, and lumbar kyphoscoliosis. The serum alkaline phosphatase was markedly elevated (1879 U/L), phosphorus was low (1.7 mg/dL), and calcium was low normal (8.9 mg/dL). The 25-hydroxy-vitamin D level was low (7.7 pg/mL) and the parathyroid hormone level was markedly elevated (114 pg/mL). The published radiographs are diagnostic of advanced rickets, showing diffuse osteopenia, frayed metaphyses, widened epiphyseal plates, and a pathologic fracture of the ulna. The patient was treated with ergocalciferol and calcium supplements. The published growth chart demonstrates the dramatic response to therapy. Gross motor milestones were fully regained within 6 months. The prominent neuromuscular manifestations shown by this patient serve as a reminder that rickets should be considered in the differential diagnosis of motor delay. (ABSTRACT TRUNCATED)
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PMID:Severe nutritional deficiencies in toddlers resulting from health food milk alternatives. 1133 66

1. On a low calcium intake hypercalcemia tended to disappear in chronic hyperparathyroidism on a given dose of parathormone (as large as 6 units per kg.), apparently due to the reduction of a readily available calcium reserve. An increase of either the calcium intake or of the daily dose of parathormone caused a rise of serum calcium and symptoms of overdosage. 2. Hypocalcemia developed in chronic hyperparathyroidism in young puppies on a low calcium diet. Tetany occurred at a calcium level which was higher and a phosphorus level which was lower than in tetania parathyreopriva of young puppies. About 0.1 gm. of calcium daily was apparently sufficient to maintain the serum calcium at a normal level. 3. The serum phosphorus in chronic hyperparathyroidism in young puppies continued at or rose above the high level normal for young animals. Toward the end of long periods of treatment on large parathormone doses (about 5 units per kg.) serum phosphorus approached normal levels, pronounced hypercalcemia was absent but hypotonia and other symptoms of hyperparathyroidism were present. 4. A single dose of parathormone caused early in the treatment and on liberal calcium intakes a more marked relative rise of serum calcium than in normal adult dogs, confirming previous observations (5, 8). Later in the treatment and on low calcium intakes this effect was greatly reduced. Serum phosphorus rose after a single injection of parathormone, even when the effect on the serum calcium was slight or absent. 5. The continued effect of parathormone on serum calcium after prolonged periods of treatment, and the modified response of the serum phosphorus indicate tolerance due to some compensation, rather than immunity. 6. The bone lesions, presenting the essential features of ostitis fibrosa cystica (von Recklinghausen's disease) in varying degrees of severity, depending on the relation of the parathormone dose to the calcium intake and to the duration of the treatment, were most prominent on low calcium intakes, which permitted the use of large doses of parathormone without fatal hypercalcemia and without symptoms of overdosage. 7. Clinical and experimental hyperparathyroidism are compared and discussed.
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PMID:PARATHORMONE DOSAGE AND SERUM CALCIUM AND PHOSPHORUS IN EXPERIMENTAL CHRONIC HYPERPARATHYROIDISM LEADING TO OSTITIS FIBROSA. 1986 66

Phosphorus is an essential substance in our body, and hypophosphataemia (HP) is well-described in rickets, refeeding syndrome, diabetic ketoacidosis (DKA), and in chronic alcohol-abuse. However, to our knowledge, HP among severely-malnourished children has not been studied in detail, and information on prevalence, severity, and treatment is scarce. Currently, there are only a few published case reports of HP. This case series describes three cases of HP that presented to Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Our first case required mechanical ventilation for respiratory distress associated with severe hypokalaemia (K 1.1 mmol/L) and moderate hypophosphataemia (P 2.1 mg/dL). The second case presented with severe sepsis which was associated with symptomatic hypocalcaemia (Ca 1.68 mmol/L), hypokalaemia (K 1.82 mmol/L), and severe hypophosphataemia (P 0.9 mg/dL). The third case presented with pneumonia and sepsis which were complicated by hypokalaemia (K 2.05 mmol/L) and severe hypophosphataemia (P 1.1 mg/dL). Marked lethargy and severe hypotonia were associated with HP in all of these cases. Manifestations of HP are diverse and can occur in association with other electrolyte imbalances, especially among malnourished children. Malnutrition, combined with sepsis, is one of the major killers of children younger than 5 years of age, and both malnutrition and sepsis can cause HP. It is concluded that the underlying causes of morbidity, including HP, should be actively sought and treated to reduce the mortality of children aged below five years.
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PMID:Hypophosphataemia among severely-malnourished children: case series. 2330 16

A 14-year-old Caucasian girl with a history of primary hypoparathyroidism and unstable calcium and phosphorus levels and on ongoing treatment was admitted to the Department of Pediatric Nephrology because of the onset of nephrocalcinosis and difficulties achieving normocalcemia. Coexistence of hypoparathyroidism, oral candidiasis, dental enamel hypoplasia, and subclinical Hashimoto's disease was strongly suggestive for autoimmune polyglandular syndrome (APS) type I. One of the clinical implications of this diagnosis is the high probability of future occurrence of adrenal insufficiency and hence the importance of maintaining a high level of suspicion in case of the onset of symptoms like weakness, fainting, hypotonia, or hyperkaliemia. Addison's disease would, in fact, be quite challenging for the future management of this patient.This clinical quiz highlighted the importance of careful evaluation of all multiorgan symptoms occurring in a patient to prevent further complications.
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PMID:Rare case of nephrocalcinosis in a 14-year-old girl: Questions. 2738 92


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