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 study of 11 autopsied cases of the cerebro-hepato-renal syndrome of Zellweger (ZS) is reported. All cases had severe, persistent congenital hypotonia, hepatic lobular disarray, renal cortical cysts and pulmonary hypoplasia. Many had cardiovascular malformations, hepatomegaly, cerebral cortical gyral maldevelopment and pancreatic islet hyperplasia. Additional, less frequent findings are delineated. Results of iron content studies of hepatic and renal tissues are related to age of survival and possible development of fibrosis.
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PMID:Studies of malformation syndromes of man XIB: the cerebro-hepato-renal syndrome of Zellweger: comparative pathology. 124 88

Peroxisome-deficient disorders including Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease are characterized by hypotonia, psychomotor delay, hepatomegaly and dysmorphism. Multiple peroxisomal enzymes are deficient in these disorders probably due to the defect of transport machinery of enzymes. Defects of beta-oxidation enzymes causes an accumulation of very-long-chain fatty acids, which is closely related to the pathogenesis. Catalase, a marker enzyme of peroxisome, is distributed in the cytosol. Immunocytochemical staining of peroxisomes using anti-catalase is a useful tool for prenatal and postnatal diagnosis. Although the primary etiology of peroxisomal deficiency has not been determined, genetic heterogeneity was clarified by complementation studies. At least 8 genes are involved in the formation of functional peroxisomes.
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PMID:[Clinical biochemical and genetic aspects of peroxisome-deficient disorders]. 137 33

In this paper, we describe a baby male born to healthy non-consanguineous parents presenting at birth with hypotonia and seizures. Additional salient clinical features included the development of glaucoma, the absence of significant facial dysmorphism and the absence of liver enlargement or renal cysts. The patient died at the age of 3 months. At autopsy, liver fibrosis and kidney glomerulosclerosis were noted. Neuropathological findings included pachygyria of the olivary nuclei and cerebellar neuronal heterotopias. There was no evidence for a demyelinating process. Biochemically, the patient was found to have elevated plasma levels of very-long-chain fatty acids (VLCFA) and abnormal bile acid intermediates, whereas other indicators of peroxisomal function (plasmalogen biosynthesis and plasma pipecolic acid) were normal. Catalase staining of a liver biopsy specimen revealed peroxisomes to be present in normal numbers, although some were abnormally large. Trilamellar inclusions typical of a peroxisomal fatty acid oxidation defect were present in macrophages. Indeed, beta-oxidation of the very-long-chain fatty acid hexacosanoic acid (C26:0) was found to be strongly deficient. Fatty acyl-CoA oxidase activity in the patient's liver was normal, however. Furthermore immunocytochemical studies using antibodies against acyl-CoA oxidase, bifunctional protein and peroxisomal thiolase, revealed the normal localization of all three enzyme proteins within the peroxisomes. We suggest that our patient has a selective peroxisomal beta-oxidation defect, a recently identified heterogeneous group of early-onset peroxisomal disorders distinct from the Zellweger syndrome and other generalized peroxisomal disorders.
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PMID:Neonatal seizures and severe hypotonia in a male infant suffering from a defect in peroxisomal beta-oxidation. 148 48

Several childhood multisystem disorders with prominent ophthalmological manifestations have been ascribed to the malfunction of the peroxisome, a subcellular organelle. The peroxisomal disorders have been divided into three groups: 1) those that result from defective biogenesis of the peroxisome (Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease); 2) those that result from multiple enzyme deficiencies (rhizomelic chondrodysplasia punctata); and 3) those that result from a single enzyme deficiency (X-linked adrenoleukodystrophy, primary hyperoxaluria type 1). Zellweger syndrome, the most lethal of the three peroxisomal biogenesis disorders, causes infantile hypotonia, seizures, and death within the first year. Ophthalmic manifestations include corneal opacification, cataract, glaucoma, pigmentary retinopathy and optic atrophy. Neonatal adrenoleukodystrophy and infantile Refsum's disease appear to be genetically distinct, but clinically, biochemically, and pathologically similar to Zellweger syndrome, although milder. Rhizomelic chondrodysplasia punctata, a peroxisomal disorder which results from at least two peroxisomal enzyme deficiencies, presents at birth with skeletal abnormalities and patients rarely survive past one year of age. The most prominent ocular manifestation consists of bilateral cataracts. X-linked (childhood) adrenoleukodystrophy, results from a deficiency of a single peroxisomal enzyme, presents in the latter part of the first decade with behavioral, cognitive and visual deterioration. The vision loss results from demyelination of the entire visual pathway, but the outer retina is spared. Primary hyperoxaluria type 1 manifests parafoveal subretinal pigment proliferation. Classical Refsum's disease may also be a peroxisomal disorder, but definitive evidence is lacking. Early identification of these disorders, which may depend on recognizing the ophthalmological findings, is critical for prenatal diagnosis, treatment, and genetic counselling.
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PMID:The peroxisome and the eye. 171 72

Peroxisomes are among the intracellular organelles of eukaryotic cells that contain specialized sets of enzymes with specific functions. Little is known of membranous components involved in assembly of the intracellular compartments. We isolated two peroxisome-deficient and mutually complementary, Chinese hamster ovary cell mutants, Z65 and Z24, which closely resembled fibroblasts from patients with autosomal recessive, peroxisome-defective disorders such as Zellweger syndrome. These patients show characteristic dysmorphism, severe hypotonia, psychomotor retardation, and peroxisomal dysfunctions and rarely survive early childhood. Here we report what seems to be the first direct cloning and characterization of a complementary DNA encoding a peroxisomal membrane protein of relative molecular mass 35,000 (Mr35K) that restores the biogenesis of peroxisomes and complements the defect of peroxisomal functions in the mutant Z65.
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PMID:Restoration by a 35K membrane protein of peroxisome assembly in a peroxisome-deficient mammalian cell mutant. 175 Sep 30

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

A male infant with glutaric aciduria II secondary to electron transfer flavoprotein: ubiquinone oxidoreductase deficiency is compared to previously reported cases of glutaric aciduria II. A common pattern of anomalies in patients with malformations (8/16) includes macrocephaly, large anterior fontanelle, high forehead, flat nasal bridge, telecanthus, and malformed ears. Abnormalities such as hypotonia, cerebral gliosis, heterotopias, hepatomegaly, hepatic periportal necrosis, polycystic kidneys, and genital defects in glutaric aciduria II are reminiscent of those in Zellweger syndrome, whereas elevations of glutaric, ethylmalonic, adipic, and isovaleric acids are quite distinctive. A unique ultrastructural alteration of the glomerular basement membrane was observed in the proposita. This manifestation may represent an early stage in renal cyst formation and provide a diagnostic criterion for glutaric aciduria II when enzyme studies are unavailable.
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PMID:Glutaric aciduria type II: review of the phenotype and report of an unusual glomerulopathy. 265 91

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

The plasma pipecolic acid concentration in two newborn infants with Zellweger syndrome at ages 4 and 10 days were 7.8 and 7.7 microM. Reported concentrations from this laboratory for normal newborn infants averaged 12 microM +/- 5.6 (SD). Both patients had the facies and severe hypotonia characteristic of the disease. Autopsy examination at age 6 days in one of these patients revealed the developmental microscopic abnormalities in brain, liver, and kidney that are associated with Zellweger syndrome. In three additional patients ages 3 1/2 weeks, 2 months, and 2 months, the pipecolic acid concentrations were 15, 17, and 25 microM. The concentrations increased to distinctly pathological levels on subsequent assays at a later age. It is concluded that the hyperpipecolatemia in Zellweger syndrome occurs postpartum and that the plasma concentrations may not be diagnostic early in life. The major manifestations of the disease, already evident at birth, cannot be attributed to pipecolatemia. Currently available data do not exclude the possibility of pipecolic acid accumulation in the brain where it has been reported to be a major metabolite of lysine. Hyperpipecolatemia of considerable degree is also consistently found in familial hyperlysinemia where it appears to be benign.
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PMID:The significance of hyperpipecolatemia in Zellweger syndrome. 308 61


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