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)

A boy born to healthy, unrelated parents, presented at birth with hypotonia and seizures. Very long chain fatty acids in the plasma were strongly elevated; bile acid intermediates and plasmalogen biosynthesis were normal. Acyl-CoA oxidase activity was normal. The patient died at the age of 3 months. The cerebellum and medulla oblongata showed neuronal migration defects. The specific biochemical basis for the impaired peroxisomal beta-oxidation has not been found. The three immunoreactive peroxisomal beta-oxidation enzymes and catalase were localized in the hepatocellular peroxisomes. Aberrant features of the peroxisomes included: a subpopulation of organelles larger than 1 micron, an amorphous nucleoid in many organelles, and invaginations of the peroxisomal membrane into the matrix. Peroxisomes in the proximal renal tubules also contained the three immunoreactive beta-oxidation enzymes. Regularly spaced trilamellar inclusions were seen in hepatic macrophages; they were much more abundant in adrenocortical macrophages. The inclusions were birefringent and resistant to acetone extraction. Distinct hepatic fibrosis had developed over a period of 2.5 months. We speculate that the impaired beta-oxidation is due to a defect at the level of the peroxisomal carnitine octanoyl or -acetyl transferase, responsible for the export of beta-oxidation products.
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PMID:Peroxisomal localization of the immunoreactive beta-oxidation enzymes in a neonate with a beta-oxidation defect. Pathological observations in liver, adrenal cortex and kidney. 194 12

We describe a relatively new syndrome in four children with characteristic facial dysmorphism, sensorineural hearing loss, severe visual impairment with retinitis pigmentosa, hypotonia, hepatomegaly, and severe developmental delay. Two patients had intracranial hemorrhage secondary to a vitamin K-responsive clotting defect; both had steatorrhea. Liver biopsy specimens in two children showed an accentuated lobular architecture with prominent fibrous bands in the portal area. In one, the ultrastructure showed accumulation of abnormal substances and occasional trilaminar structures in hepatocytes and other cells. All four patients had elevated serum phytanic acid concentrations (0.3 to 2.7 mg/dl, normal less than 0.2 mg/dl) and deficient fibroblast phytanic acid oxidase activity (0.1 to 6.7 pmol/mg protein/hr, normal 23 to 87 pmol/mg protein/hr). Serum pipecolic acid was 7 to 55 times normal, and the ratio of C26/C22 very long chain fatty acids was increased (0.10 to 0.22; normal less than 0.03). This characteristic syndrome has been described in several children and called infantile Refsum disease or phytanic acid storage disease. Its relationship to neonatal adrenoleukodystrophy, hyperpipecolic acidemia, and Zellweger syndrome is discussed.
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PMID:Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: studies in four children. 241 87

Nine cases of neonatal adrenoleukodystrophy are described. All patients had abnormal facial features, moderate to severe hypotonia, hepatomegaly, and retinitis pigmentosa. The clinical course was rapidly progressive in six cases and more protracted in three others. Biological signs of adrenal insufficiency were present in five cases. CT scan showed a demyelinating process in four patients. Trilamellar inclusions were found in the liver of four cases and dark and complex lipidic inclusions in three other cases. In the three necropsied patients there was severe alteration of the white matter involving particularly the cerebellum in two cases. Gyral and cytoarchitectonic disturbances were absent in all three cases. Increased plasma levels of very long chain fatty acids (8/8), phytanic acid (7/8) and bile fluid trihydroxycoprostanic acid (2/4) confirmed the deficiency of multiple peroxisomal enzymes. Clinical, histopathological and biochemical findings of these nine cases are compared to those reported in other neonatal adrenoleukodystrophy cases and to those of other neonatal peroxisomal disorders, that is cerebro-hepato-renal syndrome of Zellweger and infantile Refsum's disease.
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PMID:Neonatal adrenoleukodystrophy. 242 Sep 40

We reported two siblings of Leber's congenital amaurosis associated with increased level of very long chain fatty acid (VLCFA) in blood. Case 1, a 3 1/2-year-old boy had congenital blindness, severe psychomotor retardation, hepatomegaly, profound hypotonia, loss of deep tendon reflexes, muscular atrophy and weakness, and non-convulsive status epilepticus characterized by a sudden respiratory failure, and also showed a flat electroretinogram, non-pigmentary retinal degeneration, severe atrophy of the brain stem and cerebellum, hepatic fibrosis, decreased motor and sensory conduction velocities and atlanto-axial instability. Sural nerve biopsy revealed severely decreased number of total myelinated fibers without remarkable demyelination or remyelination. Case 2, an elder sister of case 1, with pigmentary retinal degeneration, hepatomegaly and pericarditis had died at 3 months. Autopsy revealed hypomyelination and heterotopy of the cerebral white matter, hepatic fibrosis, renal microcysts and normal adrenal cytoarchitecture. In case 1, the level of VLCFA was increased twofold and sevenfold of controls in serum and in red cell membrane, respectively. Phytanic or trihydroxycholestanoic acid was not detected in the serum and bile. Normal shaped peroxisomes were definitely recognized in biopsied liver by means of electronmicroscopic histochemistry. From the above findings, these patients was thought to be a new variant of peroxisomal disorders relating to degradation of VLCFA, other than Zellweger syndrome, infantile Refsum disease and infantile adrenoleukodystrophy. It was concluded that peroxisomal functions should be studied in cases of Leber's congenital amaurosis.
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PMID:[Two siblings of Leber's congenital amaurosis with an increase in very long chain fatty acid in blood: relationship between peroxisomal disorders and Leber's congenital amaurosis]. 278 58

A male infant with typical clinical and biochemical findings of Zellweger syndrome, but in whom hepatic peroxisomes were detected by electron microscopy, had profound hypotonia, hepatomegaly, typical facial appearance including large fontanelle and frontal bossing, convulsions, panaminoaciduria, and hyperammonemia. He died of liver failure at age 5 months. There were increased levels of very long chain fatty acids and trihydroxycoprostanic acid in serum, and increased excretion of dicarboxylic acids and tyrosine metabolites in the urine. Levels of peroxisomal enzymes, acyl coenzyme A oxidase, bifunctional protein, 3-ketoacyl coenzyme A thiolase, and dihydroxyacetone phosphate acyltransferase in the liver tissue from the patient were all deficient, findings consistent with Zellweger syndrome. However, immunocytochemical study and electron microscopic examination of the liver at autopsy revealed that hepatic peroxisomes were present at a level similar to that in a control subject. These observations suggest further heterogeneity in Zellweger syndrome and a different pathogenesis in this variant case.
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PMID:Zellweger-like syndrome with detectable hepatic peroxisomes: a variant form of peroxisomal disorder. 318 38

A 4.5-year-old male patient is described with chorioretinopathy, minor facial anomalies, delayed closure of the fontanel, mental retardation, moderate hypotonia, epilepsy and hepatic fibrosis. Postural control, intentional vocalising and manual dexterity were superior to the performance of patients with classical Zellweger syndrome (ZS). Morphologically distinct peroxisomes were absent in the liver. In blood elevated pipecolic acid levels and abnormal levels of bile acid intermediates were found. The plasmalogen content of erythrocytes was normal. In fibroblasts we found an accumulation of very long chain fatty acids, decreased activity of acyl CoA:dihydroxyacetone phosphate acyltransferase, and impaired de novo biosynthesis of plasmalogens. On the basis of these clinical, ultrastructural and biochemical characteristics we assume that this patient represents a milder variant of the classical cerebro-hepato-renal syndrome of Zellweger.
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PMID:A milder variant of Zellweger syndrome. 407 50

The cerebro-hepato-renal (Zellweger) syndrome is characterised by dysmorphic features, severe muscular hypotonia, hepatic dysfunction and early death in infancy. Recently it has been shown that the disease is an inborn error of metabolism with an unusual variety of metabolic disturbances affecting pipecolic acid, bile acids, plasmalogens and very long chain fatty acids. Ultrastructural and biochemical findings confirming the diagnosis are illustrated. The syndrome is inherited as an autosomal recessive trait, prenatal diagnosis has become possible.
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PMID:[Zellweger's syndrome (cerebro-hepato-renal syndrome)--its clinical picture, morphology and biochemical diagnosis]. 408 27

We describe an infant boy with facial dysmorphism, profound hypotonia, psychomotor retardation, seizure and hepatomegaly. Biochemical study revealed elevation of very long chain fatty acids and pipecolic acid, consistent with peroxisomal disorder. He died at the age of 4 months. Electron microscopic study demonstrated decreased amounts of peroxisomes in liver and kidneys. The clinical characteristic, accompanied the biochemical and microscopic findings led to the diagnosis of Zellweger syndrome. The recognition of this syndrome is important since it is a fatal disease. The pattern of inheritance is autosomal recessive, hence genetic counseling is necessary. We emphasize that peroxisomal disorder should be included in the differential diagnosis in patients with infantile hypotonia. This patient is the first reported case of Zellweger syndrome in Thailand.
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PMID:Zellweger syndrome: first reported case in Thailand and literature review. 862 40

A female Japanese patient diagnosed with peroxisome biogenesis defect (PBD), who had hypotonia and craniofacial dysmorphism, was given supplementation of docosahexaenoic acid (DHA). Accumulation of very long chain fatty acids was revealed, and a diagnosis of PBD was made at 2 months of age because of the absence of peroxisomes, a defect in peroxisomal beta-oxidation enzymes and a decreased level of DHA in the erythrocytes. Supplementation of DHA was introduced at 3 months of age. For the first several months, psychomotor development was fairly good. The patient could laugh, brush off a blanket and play with toys at 6 months of age. However, neurological regression and convulsions occurred after 7 months of age. After recurrent respiratory infections and disturbance of the circadian rhythm, the patient died of liver failure and disseminated intravascular coagulopathy at 20 months of age. DHA may have a favorable effect on the early development of patients with PBD, but neurological deterioration cannot be prevented. Patients with a milder phenotype would be better candidates for DHA supplementation.
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PMID:Trial of docosahexaenoic acid supplementation on a Japanese patient with a peroxisome biogenesis defect. 894 14

The peroxisomal disorders belong to a group of inborn errors of metabolism due to malformation or malfunction of these subcellular organelles. Their clinical features vary with age. However, the commonest form presents in the syndrome of Zellweger with severe hypotonia, craniofacial dysmorphism, stippled calcifications, renal cortical cysts and liver dysfunction. By means of complementation very long tests 17 different genotypes have been identified and in 15 of these there were neurological changes. Diagnosis requires recognition of the clinical features, raised levels of very long chain fatty acids, and radiological and neuroimaging studies.
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PMID:[Clinical features of the peroxisomal disorders]. 973 63


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