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 male infant with type I hereditary tyrosinemia developed a phenylalanine-tyrosine deficiency syndrome after receiving a synthetic diet which was low in these amino acids. The syndrome was characterized by growth failure, anorexia, lethargy, and hypotonia. Hypophenylalaninemia and hypotyrosinemia were discovered. The blood concentration of most other amino acids were increased. Supplementation of the patient's diet with phenylalanine and tyrosine resulted in a prompt and dramatic reversal of both clinical and biochemical abnormalities. Dietary therapy had no effect on the child's hepatic cirrhosis.
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PMID:Phenylalanine-tyrosine deficiency syndrome as a complication of the management of hereditary tyrosinemia. 83 7

Four children had progressive degeneration of the cerebral cortex, with hepatic cirrhosis. They and four previously described ones, are representative of a distinct form of hepatocerebral degeneration. Onset of the neurological disorder is between ages 1 and 3 years, at times with mild developmental delay. Explosive onset of intractable convulsions, leaving the child in a stuporous and demented state, is characteristic. Generalized hypotonia or hemiparesis were observed in several affected children. Clinical evidences of hepatic disease, including ascites and jaundice, occurred late, if at all. The illness ended fatally within ten months of onset of convulsions. Pathological findings in the brain are neuronal loss and gliosis, in a pattern that is indistinguishable from that in degeneration of the cerebral gray matter in infancy (Alpers disease). The hepatic lesions consist of cirrhosis or of subacute hepatitis, with superimposed fatty infiltration of hepatocytes. The disorder is genetically determined, with recessive inheritance.
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PMID:Infantile diffuse cerebral degeneration with hepatic cirrhosis. 125 62

Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction.
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PMID:Liver involvement in Alpers disease. 186 Dec 11

Orthotopic liver transplantation was performed in a 29-year-old woman because of increasing decompensation of HBs-antigen positive post-hepatitic cirrhosis. Postoperatively she developed a mild rejection reaction and diabetes mellitus. Thirteen months after the transplant she conceived twins. This high risk pregnancy was complicated by a febrile viral infection with purulent tracheobronchitis at 9 weeks and a threatened abortion at 11 weeks. At 33 weeks there was a sudden drop in haemoglobin due to a minor uterine rupture which necessitated cesarean section. The female infants--of development in keeping with the dates--showed no clinical or ultrasound evidence of any malformations. Apart from initial difficulties--asphyxia (second twin), fluctuating glucose and calcium levels, an episode of neonatal jaundice which required phototherapy, reluctance to suck and hypotonia--the further development of both twins proceeded normally. The maternal diabetes disappeared after delivery, HBs-antigen remained negative and the HBs-antibody titre rose. The patient has remained in good condition, both mentally and physically.
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PMID:[Twin pregnancy after liver transplantation]. 235 62

The cerebro-hepato-renal syndrome is a rare familial malady with cerebral, renal, and skeletal abnormalities, severe hypotonia, cirrhosis, iron and lipid storage, and death within 6 months. Correlated electron microscopic, histochemical, and biochemical studies demonstrate defects in two oxidative organelles. Peroxisomes cannot be found in hepatocytes and renal proximal tubules. In hepatocytes and cortical astrocytes, mitochondria are distorted in their appearance and glycogen stores are increased. Oxygen consumnption of brain and liver mitochondrial preparations with succinate and with substrates reducing nicotinamide adenine dinucleotide is markedly diminished, but the consumption is normal with ascorbate and tetramethylphenylenediamine, which suggests a defect in electron transport prior to the cytochromes. Histochemical studies of mitochondrial oxidation point to a defect between the succinate dehydrogenase flavoprotein and coenzyme Q, possibly in the region of nonheme iron protein.
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PMID:Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. 473 55

A neonate with deficiency of branching enzyme (glycogenosis type IV) presented symptoms of severe hypotonia pre- and postnatally, and dilated cardiomyopathy in early infancy. The classical clinical manifestation of liver cirrhosis was not present, although amylopectin-like inclusions were found in the hepatocytes. In contrast to a previous report, the neurons in the brain stem and spinal anterior horns contained PAS-positive, diastase-resistant deposits. The combined involvement of the muscles and motor neurones could account for the severity of hypotonia. The muscle biopsy, electromyogram and biochemical and enzyme assays were helpful in establishing the diagnosis.
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PMID:Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis. 805 7

The authors present and discuss the care of a nine-month-old with neonatal adrenoleukodystrophy who required general anaesthesia for gastrointestinal endoscopy. Neonatal adrenoleukodystrophy is an inherited disorder of peroxisomal enzymes. Anaesthetic care may be affected by the presence of hypotonia, liver function abnormalities, gastroesophageal reflux, and impaired adrenocortical function. Preoperative sedation is contraindicated because of the risk of precipitating airway obstruction due to pre-existing hypotonia. Anaesthetic induction and tracheal intubation should be performed to minimize the risk for aspiration of gastric contents. The choice of muscle relaxant should take into account the pre-existing hypotonia as well as the possibility of hyperkalaemia in response to succinylcholine. Anaesthetic agents known to decrease the seizure threshold should be avoided in patients with a seizure disorder. In addition, anaesthetic agents that rely on the liver for metabolism should be used with caution in patients with cirrhosis. When time permits, these patients should be screened for adrenocortical insufficiency before surgery, and perioperative steroid coverage is advisable when preoperative testing of adrenocortical function is not feasible. While these patients eventually die after progressive deterioration, full recovery from the effects of anaesthesia and surgery can be achieved with attention to neurological, metabolic, and physical problems.
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PMID:Anaesthesia for the patient with neonatal adrenoleukodystrophy. 811 45

Peroxisomes or microbodies are peculiar subcellular organelles with an important role in the metabolism of a variety of different organic compounds. Particularly they are an important site of bile acids synthesis. Some hepatic diseases, mainly cholestatic, can to be reconnected at disorders of bile acids synthesis by these organelles. From the biochemical point some diseases present alterations of the cholesterol side chain (Zellweger syndrome, pseudo-Zellweger syndrome, infantile Refsum's disease, neonatal adrenoleukodystrophy), other diseases present errors involving the steroid nucleus (familial giant cell hepatitis). Zellweger disease or cerebro-hepato-renal syndrome is characterized clinically by skeletal changes, muscle hypotonia, renal cysts, psychosomatic retardation and persistent cholestasis and from the ultrastructural standpoint by the virtual absence of liver cell peroxisomes. Pseudo-Zellweger disease shows many of the clinical features of Zellweger disease but differs from this condition on account of the presence of abundant peroxisomes in the liver cells. Infantile Refsum's disease and neonatal adrenoleukodystrophy show typical clinical disorders and liver damage leading to cirrhosis. "Familial giant cell hepatitis" is characterized by jaundice from the first days of life, hepatosplenomegaly, cholestasis, lack of physical malformations. The disorder is due to defective biosynthesis of the bile acids with formation of allo-bile acids.
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PMID:[Liver pathologies due to peroxisome disorders]. 818 91

Type IV glycogenosis or Andersen disease is characterized by a deficiency in branching enzyme. This rare disease is exceptionally seen at birth. The clinico-pathological data are then typical: severe hypotonia with hypoventilation and cellular storage, without any hepatosplenomegaly. The stored material is PAS positive, sometimes made of crystals and appeared birefringent under polarized light. Granulo-filamentous inclusions are shown by electron microscopy, essentially observed in muscle and liver without cirrhosis. Death occurs rapidly. The present case was typical. It is the eleventh reported case in the literature.
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PMID:[Congenital variant of type IV glycogenosis. Anatomoclinical report of a case]. 909 Sep 36

Glycogen storage disease type IV (GSD-IV) is an autosomal recessive genetic disorder due to a deficiency in the activity of the glycogen branching enzyme (GBE). A deficiency in GBE activity results in the accumulation of glycogen with fewer branching points and long, unbranched outer chains. The disorder results in a variable phenotype, including musculoskeletal, cardiac, neurological, and hepatic involvement, alone or in continuum, which can be identified at any stage of life. The classic form of GSD-IV is a hepatic presentation, which presents in the first 18 months of life with failure to thrive, hepatomegaly, and cirrhosis that progresses to liver failure, resulting in death by age 5 years. A severe congenital musculoskeletal phenotype with death in the neonatal period has also been described. We report an unusual case of congenital musculoskeletal presentation of GSD-IV with stable congenital hypotonia, gross motor delay, and severe fibro-fatty replacement of the musculature, but no hepatic or cardiac involvement. Molecular analysis revealed two novel missense mutations with amino acid changes in the GBE gene (Q236H and R262C), which may account for the mild phenotype.
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PMID:Non-lethal congenital hypotonia due to glycogen storage disease type IV. 1652 37


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