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)

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and gamma-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.
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PMID:Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency. 1501 27

Increased muscle extensibility and passivity characterize infantile hypotonia. It may reveal a peripheral neuromuscular disease as well as a disorder of the central nervous system. Electrodiagnostic studies in newborn and young infants are useful to guide the indication of other complementary investigations. Signs of denervation on needle electromyography strongly suggest infantile spinal muscular atrophy. Electrodiagnostic findings can distinguish rare conditions mimicking spinal muscular atrophy that are obstetrical tetraplegia and severe congenital neuropathies. Nerve conduction velocities are severely slowed in hereditary sensorimotor neuropathies and neurodegenerative disorders. Myopathic changes on needle electromyography are associated with congenital muscular dystrophies and structural or metabolic congenital myopathies. In congenital myotonic dystrophy, myotonic discharges can be recorded in the infant as well as in his/her mother. Myopathic changes may also be detected in collagen disorders, in cases of muscular atrophy secondary to hypomotility or malnutrition, and in patients with congenital myasthenic syndrome. Repetitive nerve stimulations are required to characterize myasthenic syndromes. Finally, normal results of electrodiagnostic studies constitute a relevant information that moves diagnostic procedures to search for central nervous system disorders. Benign congenital hypotonia is a quite rare condition that is diagnosed retrospectively, when hypotonia is strictly isolated and recovers completely before 2 years of age.
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PMID:[The role of electrodiagnostic studies in the diagnosis of hypotonia in infancy]. 1524 76

Congenital disorders of glycosylation (CDG) represent a newly delineated group of inherited multisystem disorders characterized by defective glycoprotein biosynthesis. In the present study we report and discuss the clinical and neuropathological findings in a newborn with CDG type Ia (CDG-Ia). The patient presented mild dysmorphic facial features, inverted nipples, progressive generalized edema, hypertrophic cardiomyopathy, hepatosplenomegaly, muscular hypotonia and had severe hypoalbuminemia. Deficiency of phosphomannomutase (PMM)-2 activity was detected. Molecular analysis showed V231M/T237R mutations of the PMM2 gene. Muscular biopsy, disclosed myopathic alterations with myofibrillar disarray by electron microscopy. The patient died at 1 month of age of circulatory and respiratory failure. Autopsy showed liver fibrosis and renal abnormalities. Neuropathological abnormalities were mainly confined to the cerebellum. Histological and immunocytochemical examination of cerebellar tissue showed partial atrophy of cerebellar folia with severe loss of Purkinje cells, granular cell depletion and various morphological changes in the remaining Purkinje cells and their dendritic arborization. Autopsy findings confirm the complexity of the CDG-Ia syndrome, and indicate that CDG-Ia is a distinct disease entity, which can be differentiated from other neurological disorders and other types of CDG, not only clinically, but also based on unique pathological findings. The data proved useful in determining the underlying disease process associated with a defective N-glycosylation pathway.
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PMID:Congenital disorder of glycosylation type Ia: a clinicopathological report of a newborn infant with cerebellar pathology. 1571 16

Many phenotypic manifestations have been reported in cardiofaciocutaneous (CFC) syndrome, but none, to date, are pathognomonic or obligatory. Previous histopathological studies reported findings in skin and hair; no autopsy studies have been published. We report the clinical and autopsy findings of a 7-year-old boy with severe CFC syndrome and malnutrition of psychosocial origin. Manifestations of CFC, reported previously, included macrocephaly and macrosomia at birth; short stature; hypotonia; global developmental delays; dry, sparse thin curly hair; sparse eyebrows and eyelashes; dilated cerebral ventricles; high cranial vault; bitemporal constriction; supraorbital ridge hypoplasia; hypertelorism; ptosis; exophthalmos; depressed nasal bridge; anteverted nostrils; low-set, posteriorly-rotated, large, thick ears; decayed, dysplastic teeth; strabismus; hyperelastic skin; wrinkled palms; keratosis pilaris atrophicans faciei; ulerythema ophryogenes; hyperkeratosis; gastroesophageal reflux; and tracheobronchomalacia. Additional findings, not previously reported, include islet cell hyperplasia, lymphoid depletion, thymic atrophy and congenital hypertrophy of peripheral nerves with onion bulb formations. Although the islet cell hyperplasia, lymphoid depletion, and thymic atrophy are nonspecific findings that may be associated with either CFC or malnutrition, the onion bulb hypertrophy is specific for a demyelinating-remyelinating neuropathy. These findings implicate congenital peripheral neuropathy in the pathogenesis of the developmental delays, feeding difficulties, respiratory difficulties, ptosis and short stature in this case. Additional studies of other cases of CFC are needed.
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PMID:Cardiofaciocutaneous syndrome (CFC) with congenital peripheral neuropathy and nonorganic malnutrition: an autopsy study. 1600 34

Deficiency of dihydropyrimidine dehydrogenase (DPD) is a rare inborn error of pyrimidine metabolism. To date, only about 50 patients are known worldwide. The clinical picture is varied and is not yet fully described. Most patients are diagnosed at the age of 1-3 years. We present a patient diagnosed 8 weeks postpartum. The female patient presented in the first 3 days after birth with agitation, choking, and vomiting. Six weeks later, the patient presented again with vomiting and insufficient weight gain. Metabolic screening of urine showed a strongly increased excretion of uracil and thymine, with no other abnormalities. This suggested a deficiency of DPD which was confirmed by enzyme analysis in peripheral blood mononucleair (PBM) cells (patient: activity <0.01 nmol/mg/h; controls: 9.9 +/- 2.8 nmol/mg/h). The patient was homozygous for the IVS14+1G>A mutation.MRI of the brain showed some cerebral atrophy; myelinization appeared normal. Many patients with DPD-deficiency suffer from convulsions and mental retardation, some show microcephaly, feeding difficulties, autism, and hypertonia. Our patient showed feeding difficulties and in the second half-year she developed slight motor retardation and generalized hypotonia. Further observation of the development of the patient may shed more light on the relationship between clinical symptoms and DPD deficiency. DPD deficiency may present in newborns with vomiting and hypotonia as the main symptoms.
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PMID:A neonate with recurrent vomiting and generalized hypotonia diagnosed with a deficiency of dihydropyrimidine dehydrogenase. 1706 71

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs' cycle. Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome. In this study, one Chinese case of PDHA1 deficiency was reported. The patient was a boy with normal mental development, retarded motor development, general weakness, hypotonia and areflexia. Muscle histopathological findings suggested axonal peripheral neuropathy. Brain magnetic resonance imaging at 5 years of age revealed bilateral putamina lesions and periventricular white matter demyelination, supporting the diagnosis of Leigh syndrome. A C214T mutation in exon 3 of the PDHA1 gene was detected. After the treatment of thiamin, coenzyme Q10, Lcarnitine and carbohydrates-restricted diet, his movement ability improved significantly. At present, the patient is 8 years old and has normal school life. PDHA1 deficiency is an X-linked inherited metabolic disease, which shares various clinical manifestations and leads to difficult diagnosis. This patient predominately presented with progressive weakness and was diagnosed by gene analysis.
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PMID:[Leigh syndrome due to pyruvate dehydrogenase E1 alpha subunit gene mutation: a complicated and difficult case study]. 1758 59

An eight month old male infant with protein energy malnutrition was admitted in the hospital with the history of repeated attacks of convulsion since four months of age. He was also suffering from frequent attacks of cough and cold since 6 months of age which was marked prior to admission. The infant had fair complexion, sparse fuzzy wooly hair with marked trunkal hypotonia. He had also mental retardation. Serum copper and ceruloplasmin levels were low, MRI showed prominent extraaxial spaces with gliosis, MR angiography revealed tortuosity of cerebral vessels. Microscopic examination of hair revealed pili torti. The patient was diagnosed as Menkes disease and treated symptomatically. For lack of facilities we were not able to do genetic study.
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PMID:Menkes kinky hair disease: A case report. 1880 Nov 84

Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia), major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X). The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by cytogenetic testing including FISH and/or DNA quantification methods. Management is multi-specialist and only symptomatic, with special attention to prevention of malnutrition and recurrent infections. Educational and rehabilitation support should be offered to all patients.
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PMID:Distal Xq duplication and functional Xq disomy. 1923 94

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

Objectives. To evaluate the clinical features, physical findings, diagnosis, and laboratory parameters of the patients with propionic acidaemia (PA). Methods. The records of diagnosed cases of propionic acidaemia were reviewed, retrospectively. Results. Twenty-six patients with PA had 133 admissions. The majority (85%) of the patients exhibited clinical manifestations in the 1st week of life. Regarding clinical features, lethargy, fever, poor feeding, vomiting, dehydration, muscular hypotonia, respiratory symptoms, encephalopathy, disturbance of tone and reflexes, and malnutrition were observed in 51-92% admissions. Metabolic crises, respiratory diseases, hyperammonaemia, metabolic acidosis, hypoalbuminaemia, and hypocalcaemia were observed in 30-96% admissions. Pancytopenia, ketonuria, hypoproteinemia, hypoglycaemia, and mildly disturbed liver enzymes were found in 12-41% admissions. Generalised brain oedema was detected in 17% and cerebral atrophy in 25% admissions. Gender-wise odd ratio analysis showed value of 1.9 for lethargy, 1.99 for respiratory diseases, 0.55 for anaemia, and 1.82 for hypocalcaemia. Conclusion. Propionic acidaemia usually presents with wide spectrum of clinical features and disturbances of laboratory parameters in early neonatal age. It is associated with significant complications which deteriorate the patients' quality of life. Perhaps with early diagnosis of the disease and in time intervention, these may be preventable.
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PMID:Clinical spectrum of propionic acidaemia. 2428 98


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