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)

Classical galactosaemia (McKusick 230400) is an: autosomal recessive disorder of galactose metabolism, caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT; EC 2.7.712). Most patients present in the neonatal period, after ingestion of galactose, with jaundice, hepatosplenomegaly, hepatocellular insufficiency, food intolerance, hypoglycaemia, renal tubular dysfunction, muscle hypotonia, sepsis and cataract. The gold standard for diagnosis of classical galactosaemia is measurement of GALT activity in erythrocytes. Gas-chromatographic determination of urinary sugars and sugar alcohols demonstrates elevated concentrations of galactose and galactitol. The only therapy for patients with classical galactosaemia is a galactose-restricted diet, and initially all galactose must be removed from the diet as soon as the diagnosis is suspected. After the neonatal period, a lactose-free diet is advised in most countries, without restriction of galactose-containing fruit and vegetables. In spite of the strict diet, long-term complications such as retarded mental development, verbal dyspraxia, motor abnormalities and hypergonadotrophic hypogonadism are frequently seen in patients with classical galactosaemia. It has been suggested that these complications may result from endogenous galactose synthesis or from abnormal galactosylation. Novel therapeutic strategies, aiming at the prevention of galactose 1-phosphate production, should be developed. In the meantime, the follow-up protocol for patients with GALT deficiency should focus on early detection, evaluation and, if possible, early intervention in problems of motor, speech and cognitive development.
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PMID:Classical galactosaemia revisited. 1683 75

We describe two patients affected by Barth syndrome. Their symptoms became manifest on respectively the third and first day of their lives. Clinical presentation included poor sucking, lethargy, hypotonia, hypothermia and cardiomyopathy. Laboratory findings such as hypoglycaemia, metabolic acidosis, elevated transaminases, hyperlactacidaemia and mild hyperammonaemia pointed to an inborn error of energy metabolism with possible mitochondrial involvement. Molecular analysis of the TAZ (G4.5) gene showed the c.877G > A mutation leading to the G197R amino acid substitution in patient 1, and the new splice donor c.829 + 1G > A genetic lesion in patient 2.
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PMID:Barth syndrome presenting with acute metabolic decompensation in the neonatal period. 1690 70

Patients with long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) deficiency manifest hypoketotic hypoglycemia, hepatomegaly, hypotonia, lactic acidemia, acute renal failure, cardiomyopathy, and sudden death. We describe four novel mutations of the alpha- and beta-subunits of the mitochondrial trifunctional protein in four patients from three unrelated families. Their plasma acylcarnitine profiles suggested the presence of LCHAD deficiency by demonstrating highly elevated 3-hydroxyacyl carnitines by tandem mass spectrometry (MS/MS). Patients 1 and 2 had siblings who had died of lactic acidemia during the neonatal period. These patients also manifested lactic acidemia and died in the neonatal period. Patient 3 had a family history of Reye-like syndrome. She exhibited acute renal failure, rhabdomyolysis, pericardial effusion, and myopathy at the age of 12 years. DNA analysis of patients 1 and 2 revealed homozygosity for a c.1689+2T>G mutation of the HADHA gene, resulting in the skipping of exon 16 with an in-frame 69-bp deletion. Patient 3 was a compound heterozygosity of the HADHB gene, N307D/N389D. Patient 4, a 25-month-old baby, manifested recurrent episodes of lethargy, metabolic acidosis, elevated liver enzymes, and dark urine from the age of 10 months. Mutation analysis of the HADHB gene of patient 4 identified compound heterozygosity of N114D/N307D.
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PMID:Identification of novel mutations of the HADHA and HADHB genes in patients with mitochondrial trifunctional protein deficiency. 1714 51

Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection and management of clinical complications such as scoliosis and febrile seizures. An adequate psychological and educational program with speech therapy and motor stimulation plays an important role in the global development of the patients. Final body height is difficult to predict but growth tends to normalize after puberty.
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PMID:Sotos syndrome. 1782 4

Barth syndrome presents in infancy with hypotonia, dilated cardiomyopathy, and neutropenia. We report a patient whose family history included two males who had died suddenly at the age of 15 days and 2 years, respectively. The index case presented with acute metabolic decompensation at 13 days of age. Within 8 h of presenting with metabolic acidosis (pH 7.13), lactic acidemia (18.5 mmol/l), hyperammonemia (375 microg/dl), hypoglycemia (25 mg/dl), and coagulopathy, the patient developed respiratory failure and required intubation. The diagnosis was established by the presence of left ventricular noncompaction and molecular analysis (c.C153G or Y51X mutation of the TAZ gene). The gene product, taffazin, is a homologue of the glycerolipid transferases involved in the phospholipid metabolism as tetralinoleoyl-cardiolipin, a component of the mitochondrial inner membrane. In conclusion, mutations in taffazin impair mitochondrial respiratory chain complexes, which may results in the acute metabolic decompensation and sudden death; cardiac transplantation is the only possibility at the present time.
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PMID:Acute metabolic decompensation and sudden death in Barth syndrome: report of a family and a literature review. 1784 86

The report presents a definition and causes of syncope in children. Syncope differs from other states with loss of consciousness by causes leading to decreased perfusion and resultant transient cerebral dysfunction with decreased muscle tone. The most common causes of syncope noted in almost 15% of children are neurocardiogenic. This group includes vasovagal, carotid sinus reflexive, situational (coughing, dysphagia, micturation and defecation disturbances) and post-exercise syncope. Another group is represented by orthostatic syncope that may be triggered by primary and secondary dis-autonomy, decreased blood volume (hemorrhage, diarrhea, Addison's disease), some medications and substances of abuse (alcohol). An important group, accounting for 2%-6% of all cases, are cardiogenic syncope, caused mainly by congenital/acquired obstructive cardiac sub- and valvar heart defects, various cardiomyopathies, some heart tumors (e.g. myxoma), exudative pericarditis, pulmonary embolus and hypertension, congenital and acquired coronary anomalies, various significant brady-tachyarrhythmias (sick sinus syndrome, supra- and ventricular tachycardias, congenital and acquired atrio-ventricular blocks). Subclavian steal syndrome as the cause of syncope is exceptional in children. Syncope does not include loss of consciousness due to neurological and metabolic (hypoglycemia) causes, hypoxia, hyperventilation with hypocapnia or CO intoxication. Differential diagnosis should also include pseudo-syncope (hysteria). Preliminary diagnostic management should include a detailed medical history, including family history, on the frequency and circumstances of syncope, sudden deaths, a physical exam with orthostatic assessment of peripheral blood pressure and standard ECG (heart rate, intraventricular and atrioventricular conduction defects, cardiac hypertrophy, arrhythmias, L-QT, changes in ST-T). Further specialist tests depend on preliminary findings.
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PMID:[Syncope in children and adolescents]. 1843 21

GLUT-1 protein is the principal glucose transporter across the blood-brain barrier. GLUT-1 deficiency results in a syndrome of infantile seizures refractory to anticonvulsive drugs, developmental delay, acquired microcephaly and neurologic manifestations including spasticity, hypotonia, and ataxia. A low cerebrospinal fluid glucose concentration in the absence of hypoglycaemia is pathognomonic of glucose transporter deficiency syndrome. Ketogenic diet is an effective treatment of epileptic manifestations but it has less effect on the cognitive symptoms. We report on a child who presented with paroxistical events often occurring prior to meals, developmental delay, microcephaly and spasticity. CSF and serum glucose levels measured simultaneously showed a CSF/serum glucose ratio of 0.39. Molecular analysis identified a heterozygous novel mutation.
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PMID:[GLUT-1 deficiency syndrome or De Vivo disease: a case report]. 1855 84

Propionic acidemia is an autosomal recessive disorder as a result of a deficient activity of propionyl-CoA carboxylase. Propionyl CoA is metabolized by propionyl-CoA carboxylase to methylmalonyl CoA. Propionic acidemia is a major cause of ketotic hyperglycinemia. This disorder is characterized by episodic vomiting, dehydratation, feeding intolerante, lethargy, hypotonia, metabolic acidosis, ketosis and hyperammonemia. The patient presented herein was a full-term female newborn with encephalopathy in the first days of life. She presented hypoglycemia, metabolic acidosis with increased anion gap, ketosis, hyperammonemia, anemia, leukopenia and thrombocytopenia. The brain ultrasonography was normal. The tandem mass expectrometry done by Pediatrix was abnormal, with the acylcarnitine results consistent with an organic acidemia. The parents are consanguineus and have a history of abortus, miscarriage and neonatal death, characteristics suggestive of the presence of genetic defects.
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PMID:[Neonatal onset of organic acidemia (propionic) diagnosed by tandem mass spectrometry]. 1864 57

The mechanism of dead-in-bed syndrome (DBS), a rare but devastating condition that mainly affects young type 1 diabetes patients, remains mysterious. A new theory is proposed to explain this syndrome. This theory suggests that repeated episodes of hypoglycaemia-induced adaptation in orexin-A neurons cause (i) defective awakening and (ii) hypotonia of upper airway muscles during sleep. Consequently, due to the combined effect of these factors, long-term exposure of intermittent hypoxia occurs, leading to a combination of factors - such as depression of ventilation, increase in sympathetic tone, fluctuations in intrathoracic pressure and cardiac arrhythmias - these in conjunction with an underlying cardiovascular pathology (genetically inherited or acquired) cause cardio-respiratory failure and thus sudden death during sleep. This mechanism can be generalized to explain other cases of sudden unexplained nocturnal deaths including sudden infant deaths (SIDs).
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PMID:The mechanism of dead-in-bed syndrome and other sudden unexplained nocturnal deaths. 1960 34

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation. SCADD is biochemically characterized by increased C4-carnitine in plasma and ethylmalonic acid in urine. The diagnosis of SCADD is confirmed by DNA analysis showing SCAD gene mutations and/or variants. SCAD gene variants are present in homozygous form in approximately 6% of the general population and considered to confer susceptibility to development of clinical disease. Clinically, SCADD generally appears to present early in life and to be most frequently associated with developmental delay, hypotonia, epilepsy, behavioral disorders, and hypoglycemia. However, these symptoms often ameliorate and even disappear spontaneously during follow-up and were found to be unrelated to the SCAD genotype. In addition, in some cases, symptoms initially attributed to SCADD could later be explained by other causes. Finally, SCADD relatives of SCADD patients as well as almost all SCADD individuals diagnosed by neonatal screening remained asymptomatic during follow-up. This potential lack of clinical consequences of SCADD has several implications. First, the diagnosis of SCADD should never preclude extension of the diagnostic workup for other potential causes of the observed symptoms. Second, patients and parents should be clearly informed about the potential lack of relevance of the disorder to avoid unfounded anxiety. Furthermore, to date, SCADD is not an optimal candidate for inclusion in newborn screening programs. More studies are needed to fully establish the relevance of SCADD and solve the question as to whether SCADD is involved in a multifactorial disease or represents a nondisease.
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PMID:Clinical aspects of short-chain acyl-CoA dehydrogenase deficiency. 2042 31


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