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

We report the results of a two-part study examining the frequency of symptoms and other findings associated with neonatal polycythemia. In the first part of the investigation, we evaluated the occurrence and features of the disorder in a cohort of 3,768 infants born at our institution that had been screened for the disorder during a 4-year period. Fifty-five infants (1.46%) had neonatal polycythemia. Of these infants, 85% had features associated with the disorder. Frequent signs and symptoms included "feeding problems" (21.8%), plethora (20.0%), lethargy (14.5%), cyanosis (14.5%), respiratory distress (9.1%), jitteriness (7.3%), and hypotonia (7.3%). Other findings included hypoglycemia (40.0%) and hyperbilirubinemia (21.8%). Of the polycythemic infants, 14.5% had no clinical symptoms or associated laboratory abnormalities. In the second portion of the study, we reviewed the features of polycythemia in all infants so diagnosed who were born in United States Army hospitals, worldwide, during a 5-year period. There were 220,050 infants born during this period; 932 (0.42%) were diagnosed as having neonatal polycythemia. Frequent findings were hyperbilirubinemia (33.5%), hypoglycemia (13.0%), and respiratory distress (6.6%). In this large group, only 13 (1.4%) had necrotizing enterocolitis, and nine (1.0%) were thrombocytopenic. Several findings among the 932 infants were unexpected. Six of the infants (only one premature) had intracranial hemorrhages. Additionally, three of the 932 had gonadal dysgenesis and three had cystic fibrosis. We found that premature infants were not less prone to having polycythemia and that the overall frequency of the disorder was less than that which has been previously reported.
 ...
PMID:Neonatal polycythemia: frequency of clinical manifestations and other associated findings. 372 98

Fumaric aciduria (fumaric acidemia, fumarase deficiency) is a rare inborn error of metabolism caused by deficient activity of fumarate hydratase, one of the constituent enzymes of the Krebs tricarboxylic acid cycle. We describe the clinical and imaging features of this disease arising from a consanguineous pedigree in 8 patients in the southwestern United States. Thirteen patients have been previously described in the medical literature. Our patients presented with an early infantile encephalopathy with profound developmental retardation and hypotonia, and most experienced seizures. Previously unreported characteristics described here include structural brain malformations, dysmorphic facial features, and neonatal polycythemia. Magnetic resonance imaging showed multiple abnormalities, including diffuse polymicrogyria, decreased cerebral white matter, large ventricles, and open opercula. Fumaric aciduria should be included in the differential diagnosis of inborn errors of metabolism that cause cerebral malformations and dysmorphic features. The possibility that inborn errors of energy metabolism may cause structural malformations deserves increased recognition.
 ...
PMID:Fumaric aciduria: clinical and imaging features. 1080 28

Polycythemia vera is a sporadic myeloproliferative disorder of increased red blood cell mass affecting multiple organ systems. Associated thrombosis, hemorrhaging, and hyperviscosity commonly result in neurological manifestations, sometimes in the form of chorea and ballism. Resultant choreiform movements have been mainly described as generalized with orofaciolingual and appendicular muscle involvement, hypotonia, and hyporeflexia. Chorea has also been uncommonly reported as arising from secondary causes of polycythemia; however, the underlying pathophysiology has not been clearly elucidated. Proposed mechanisms for basal ganglia dysfunction include hypoperfusion due to venous stasis, receptor hypersensitivity in a setting of reduced catecholamine levels, and altered platelet dopamine metabolism. Magnetic resonance imaging and single-photon emission computed tomography perfusion studies have failed to reveal an anatomical or physiological basis for polycythemia vera-associated chorea, yet rare pathological examinations of deceased patients have shown signs of cerebral venous thrombosis and perivenous demyelination. Administration of neuroleptics may suppress abnormal choreiform movement; however, effective management of polycythemia vera requires serial venesections in conjunction with chemotherapy. Appropriate treatment may prolong survival to more than 10 years, although chorea may spontaneously remit, re-emerge with resurgence of disease, or continue indefinitely despite maintenance therapy.
 ...
PMID:Polycythemia and chorea. 2149 86

Mutations in the FH gene cause the deficiency of the enzyme fumarase (fumarate hydratase, EC 4.2.1.2) which result in autosomal recessive fumaric aciduria in early childhood with failure to thrive, seizures, developmental delay, mental retardation, hypotonia and sometimes with polycythemia, leukopenia, and neutropenia. Many children with fumarate hydratase deficiency do not survive infancy or childhood; those surviving beyond childhood have severe psychomotor retardation. Recently, FH gene was also identified as a "non-classical" tumor suppressor gene and heterozygous mutations were shown to cause multiple cutaneous and uterine leiomyomas as well as hereditary leiomyomatosis and renal cell cancer. A male patient who was referred to investigate the etiology of psychomotor retardation was later diagnosed to have fumaric aciduria due to the combination of a previously known (c.1431_1433dupAAA) and a novel (c.782G>T) mutation. The patient had an unusually mild clinical course without acidotic attacks. Interestingly his father who was heterozygous for the c.1431_1433dupAAA mutation in the FH gene had cutaneous leiomyoma.
 ...
PMID:Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene. 2361 58

Manganese (Mn) is an essential element in trace quantity but large amounts are toxic. A novel hereditary disorder encompassing high blood Mn levels, dystonia, polycythemia, distinctive T1 hyperintense signals in the basal ganglia on magnetic resonance imaging (MRI) brain, and chronic liver disease was recently described. The disorder is caused by mutations in a Mn transporter encoding gene SLC30A10. We are reporting the clinical features of this rare disorder in two Saudi brothers. The older brother presented with progressive gait difficulties, hypotonia, intermittent dystonia, polycythemia, and characteristic T1-hyperintense lesions on MRI brain. SLC30A10 sequencing identified a novel missense mutation. The younger brother was identified in presymptomatic phase on family screening. Chelation therapy with disodium calcium edetate (ethylenediaminetetraacetic acid, EDTA) led to stabilization of gait, reduction in Mn levels, and resolution of polycythemia. We wish to highlight the atypical neurologic presentation, a novel missense mutation, and beneficial effect of EDTA in this rare disease.
 ...
PMID:Atypical Neurologic Phenotype and Novel SLC30A10 Mutation in Two Brothers with Hereditary Hypermanganesemia. 2917 35