Hypotonia deficiency

Patients with complex I deficiency may also present with severe congenital lactic acidosis, hypotonia, weakness, cardiomyopathy, and cardiorespiratory failure caus-... 

Hereditary triose phosphate isomerase (TPI) deficiency is an autosomal recessive disorder that has the most severe clinical manifestations of the erythroenzy-mopathies, including hemolytic anemia, neurological dysfunction, sudden cardiac death, and increased susceptibility to infection. Since the first description by Schneider et al. (S10), more than 25 unrelated families have been reported (Fll). Cases of decreased TPI activities associated with cat cry syndrome and pancytopenia were reported, whereas the correlation between TPI deficiency and these disorders was not clear. Although the degree of anemia is variable, most patients require blood transfusions. Neurological involvement, such as paraparesis, weakness, and hypotonia, is progressive in most cases. No specific therapy is available for the neuropathic manifestations of the disease, and most severely affected children fail to survive beyond the age of 5 years. 

Other causes of PKU secondary to defective tetrahydrobiopterin synthesis include GTP cyclohydrolase deficiency and 6-pyravoyltetrahydrobiopterin synthase deficiency. Patients with either defect have psychomotor retardation, truncal hypotonia with limb hypertonia, seizures and a tendency to hyperthermia. The intravenous administration of BH4 may lower blood phenylalanine levels but this cofactor may not readily cross the blood-brain barrier. Treatment with synthetic pterin analogs or supplementation with tryptophan and carbidopa may prove more efficacious, particularly if treatment is started early in life. 

Cobalamin-c disease remethylation of homocysteine to methionine also requires an activated form of vitamin B12. In the absence of normal B12 activation, homocystinuria results from a failure of normal vitamin B12 metabolism. Complementation analysis classifies defects in vitamin B12 metabolism into three groups cblC (most common), cblD and cblF. Most individuals become ill in the first few months or weeks of life with hypotonia, lethargy and growth failure. Optic atrophy and retinal changes can occur. Methylmalonate excretion is excessive, but less than in methylmalonyl-CoA mutase deficiency, and without ketoaciduria or metabolic acidosis. 

Succinic semialdehyde dehydrogenase deficiency. Patients have mental retardation, cerebellar disease, and hypotonia. They excrete large amounts of both succinic semialdehyde and 4-hydroxybutyric acid. There is no known therapy. 

Fructose-1,6-bisphosphatase deficiency, first describ ed by Baker and Winegrad in 1970, has now been reported in approximately 30 cases. It is more common in women and is inherited as an autosomal recessive disorder. Initial manifestations are not strikingly dissimilar from those of glucose-6-phosphatase deficiency. Neonatal hypoglycemia is a common presenting feature, associated with profound metabolic acidosis, irritability or coma, apneic spells, dyspnea, tachycardia, hypotonia and moderate hepatomegaly. Lactate, alanine, uric acid and ketone bodies are elevated in the blood and urine [11]. The enzyme is deficient in liver, kidney, jejunum and leukocytes. Muscle fructose-1,6-bisphosphatase activity is normal. 

Defects of the Krebs cycle. Fumarase deficiency was reported in children with mitochondrial encephalomyop-athy. Usually, there is developmental delay since early infancy, microcephaly, hypotonia and cerebral atrophy, with death in infancy or early childhood. The laboratory hallmark of the disease is the excretion of large amounts of fumaric acid and, to a lesser extent, succinic acid in the urine. The enzyme defect has been found in muscle, liver and cultured skin fibroblasts [16]. 

Choline acetyltransferase deficiency. The distinguishing clinical feature is sudden episodes of severe respiratory difficulty and oropharyngeal (bulbar) weakness leading to apnea (cessation of respiration) precipitated by infections, fever or excitement, or occurring even spontaneously. In some patients, the disease presents at birth with hypotonia... 

Most of hyperphenylalaninemia are caused by a mutation in the PAH gene. About 5% of hyperphenylalaninemia is caused by genetic defects in the BH4-metabolizing enzymes, and called malignant-type or atypical hyperphenylalaninemia. Patients with malignant-type hyperphenylalaninemia develop neurological symptoms due to deficiency of catecholamines and serotonin, as well as hyperphenylalaninemia. For example, patients with GTP cyclohydrolase deficiency show severe retardation of development, severe muscular hypotonia of the trunk and hypertonia of extremities, convulsions, and frequent episodes of hyperthermis without infection [160,161]. 

The age of onset of symptoms of children with profound biotinidase deficiency varies from several months to 10 years old, with a mean age of presentation between 3 and 6 months old. The most common neurological features of this disorder are seizures, hypotonia, and ataxia. Myoclonic seizures are the most... 

The site and type of bone deformity seen in rickets depend on the age of the child. In a small infant, deformities of the forearms and anterior bowing of the distal tibias are more common. Clinical features such as craniotabes (areas of thinning and softening in the bones of the skull), hypotonia, and tetany are common in vitamin D-deficiency rickets, which occurs more frequently in infants 1 year old or younger. These features may be absent in calcium-deficiency rickets, which usually presents after the age of 1 year or after the child has been... 

Disorders of glycerol metabolism. Glycerol is converted to glycerol-3-phosphate by the hepatic enzyme glycerol kinase deficiency results in episodic vomiting, lethargy and hypotonia. Glycerol kinase deficiency is X-hnked. 

Tay-Sachs disease is the B-variant of GM2 gangliosidosis due to a-chain deficiency and to the subsequent deficiency of hexosaminidases A and S, buf wifh normal hexosaminidase B. Depending on fhe residual enz)me acfivify of /3-hexosaminidase, fhe onsef of symptoms may occur an)Twhere from late infancy to adulthood and are usually subclassifled into infantile (t) e 1)-, juvenile (type 2)-, chronic-, and adult-onset forms [33]. In type 1, the most common disease with a carrier frequency of 1 in 27 among Ashkenazi Jews [154], patients are normal at birth but then show s)mptoms, such as mild motor weakness, between 3 and 6 months, resulting in hypotonia, poor head control, decreasing attentiveness, and visual symptoms (cherry red... 

CPT-I deficiency (liver and muscle types) 255120 600528 601987 Carnitine palmitoyl transferase I <1 100,000 Liver disease, hypotonia, renal tubular acidosis AFLP... 

SCAD deficiency 201470 dehydrogenase >1 50,000 Developmental delay,. hypotonia, seizures AFLP, HELLP syndrome... 

A genetic disorder called GHB aciduria occurs when there is a deficiency of succinic semialdehyde dehydrogenase. Persons with this disorder have elevated concentrations of GHB in their blood, spinal fluid and urine (Gibson et al., 1998). The clinical manifestations of the increased GHB concentration can range from mild oculomotor problems and ataxia to severe psychomotor retardation, but it is most commonly characterized by mental, motor and language delay accompanied by hypotonia. 

Biotinidase deficiency A failure of biotin recycling results in an organic aciduria, developmental delay, seizures, alopecia, hypotonia and hearing loss... 

The first recognized human metabolic defect in the biosynthesis of cholesterol and isoprenoids was mevalonic aciduria [10]. Mevalonic aciduria is an autosomal recessive disorder that is quite rare, with only 30 known patients (D. Haas, 2006). In normal individuals, a small amount of mevalonic acid diffuses from cells into the plasma at levels proportional to the rate of cellular cholesterol formation. Patients with the severe, classical form of mevalonic aciduria excrete 10,000-200,000 times the normal amount of mevalonic acid because they have severely reduced amounts of mevalonate kinase activity. Their clinical features include failure to thrive, anemia, gastroenteropathy, hepatosplenomegaly, psychomotor retardation, hypotonia, ataxia, cataracts, and dysmorphic features [10]. Surprisingly, patients with severe deficiencies in mevalonate kinase show normal plasma cholesterol levels and cultured mevalonic aciduria fibroblasts have a rate of cholesterol synthesis that is half that of normal cells. Close examination of cholesterogenic enzymes in mevalonic aciduria fibroblasts has revealed a 6-fold increase in HMG-CoA reductase activity, which is postulated to compensate for the low mevalonate kinase activity. Thus, mevalonate is overproduced. 

You are examining mitochondria from muscle cells of an infant who has a deficiency in one of the enzymes in the fatty acid oxidative pathway. The mitochondria consume oxygen normally when incubated with pyruvate and malate, "with succinate, or with palmitoyl CoA (in the presence of carnitine), but the rate of oxygen utilization is decreased when the mitochondria are incubated with linoleoyl CoA in the presence of carnitine. Blood levels of carnitine in the patient are low, while the levels of an unusual acylcami-tine derivative are present in blood and urine. Analysis of this acylcamitine species using mass spectroscopy reveals that it is trans-A, cis-A decadienoyl (C10 2)-acylcamitine. The infant suffers from hypotonia (lack of muscle tone) and slow weight gain. 

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