Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myoadenylate deaminase (MADA) deficiency has been associated with symptoms of postexertional aches, cramps, weakness, and skeletal muscle dysfunction. Measurement of plasma lactate and ammonia concentrations after forearm ischemic exercise has been suggested as a screening test for this disorder. We performed forearm ischemic tests on 3 patients with histochemically defined MADA deficiency and 13 healthy control subjects, in a standardized fashion. Our results demonstrated that subject effort and/or performance during the exercise portion of testing is a critical variable. In addition to lactate and ammonia, plasma purine compounds (adenosine, inosine, and hypoxanthine) were measured. The finding of decreased purine release after exercise in MADA-deficient patients compared with that in normal individuals increases the specificity of the test and supports the hypothesis that disordered purine metabolism occurs in MADA deficiency.
 ...
PMID:Myoadenylate deaminase deficiency and forearm ischemic exercise testing. 360 85

Myoadenylate deaminase (MADA) is an enzyme which participates in the purine nucleotide cycle necessary for energy production in human skeletal muscle. Approximately 35 patients with deficiency of this enzyme have been reported; one-half experienced their initial difficulties in childhood. Children with "primary" MADA deficiency typically have symptoms including muscle cramps, stiffness, and post-exercise myalgia and weakness. In "secondary" MADA deficiency, the clinical findings have been variable with delayed motor development, hypotonia, cardiomyopathy, delayed speech development, and generalized weakness. In most cases creatine kinase determinations, nerve conduction velocity studies, and routine muscle histopathology have been normal. Diagnosis has been established by demonstrating an absence of MADA activity by either direct muscle enzyme assay or histochemical staining. In this report we describe a 12-year-old boy with primary MADA deficiency and contrast his symptoms with those of previously described pediatric patients.
 ...
PMID:Myoadenylate deaminase deficiency in children. 391 3

An X-linked recessive disease is reported in a large pedigree. The disease is characterised by a triad of dilated cardiomyopathy, neutropenia and skeletal myopathy. The untreated patients, all boys, died in infancy or early childhood from septicemia or cardiac decompensation. Ultrastructural abnormalities were observed in mitochondria in cardiac muscle cells, neutrophil bone marrow cells and to a lesser extent (0-9%) in skeletal muscle cells. Membrane-bound vacuoles were seen in neutrophil bone marrow cells. Intramuscular fat droplets were increased in type I skeletal muscle fibres. An affected patient had intermittent lactic acidemia, borderline low plasma carnitine, the latter decreasing during periods of illness, and low muscle carnitine (27% pretreatment; 35-40% posttreatment). While on treatment with oral carnitine he had less weakness and no cardiac complaints, but his neutropenia was not affected. Respiratory chain abnormalities were observed in this patient's isolated skeletal muscle mitochondria. These were: (1) diminished concentrations of cytochromes c1 + c, b and aa3 to 29, 47 and 64% of the averaged controls, and (2) a lowered P:0 ratio for oxidation of ascorbate + TMPD, with diminished uncoupler stimulated Mg2+-ATPase activity. Muscle AMP deaminase was deficient (5 resp. 17%). Only one previous report (Neustein et al. 1979) on X-linked mitochondrial cardiomyopathy exists, which probably refers to the same entity. Biochemical studies and haematological abnormalities (neutropenia) are reported for the first time.
 ...
PMID:An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. 614 97

A 2-yr-old boy had congenital hypotonia, limb weakness, exercise intolerance and one episode of myoglobinuria. Histochemical and biochemical analysis of muscle showed a combined defect of phosphorylase and AMP deaminase. DNA analysis showed that the child was homozygous for the mutations commonly found in both McArdle's disease and AMP deaminase deficiency. The father was heterozygous for both mutations. The mother was heterozygous for the myophosphorylase gene mutation and homozygous for the mutation in the AMP deaminase 1 gene.
 ...
PMID:Double trouble: combined myophosphorylase and AMP deaminase deficiency in a child homozygous for nonsense mutations at both loci. 758 Feb 37

We report a right-handed 22-year-old man with muscle atrophy. His prenatal course and the delivery were uneventful, but he walked unsupported at 15 months of the age for the first time. He was apparently well but he was in the slowest group in running in schools. He noted a difficulty in climbing up stairs at 19 years of the age, and he was admitted to our hospital for the work up when he was 22-year-old. His family history and past medical history were unremarkable. On admission, he was a slender and tall guy in no acute distress. General physical examination was unremarkable, but he had high-arched palate and high-arched feet. On neurologic examination, mental status and higher cerebral functions were normal. Cranial nerves appeared intact, however, he had a thin and long face without weakness. The sternocleidomastoid muscles appeared somewhat atrophic and were moderately weak. He was able to walk normally, however, he needed a handrail when he went up stairs. Thigh muscles and triceps surae muscles were atrophic and slightly weak (4/ 5). Muscle tone was hypotonic and no deep tendon reflexes were elicited except for jaw jerk. No ataxia or involuntary movements were seen; sensation was intact. Laboratory examination was unremarkable except for slight increase in serum CK to 145 IU/L. An ischemic forearm exercise test revealed slight elevation of lactate and pyruvate in that base line levels were 5.4 mg/dl and 0.52 mg/dl, respectively, which rose to 11.4 mg/dl and 0.85 mg/dl, respectively, 20 minutes after the initiation of the ischemic exercise. The base line serum ammonia was 102.5 micrograms/dl which decreased to 64.8 micrograms/dl at 20 minutes. A diagnostic biopsy was performed from the left quadriceps femoris muscle. The patient was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had nemaline myopathy. Opinions were divided between nemaline myopathy and debranching enzyme deficiency. The results of the ischemic exercise was not typical of glycogen storage disease, but elevations of lactate and pyruvate did not appear to be sufficient to be interpreted as normal. Histologic examination of the biopsied specimen revealed marked type I fiber predominance and abundant nemaline rods. Cytoplasmic bodies were also seen. Histologic characteristics were consistent with the diagnosis of nemaline myopathy. The possibility of concomitant presence of AMP deaminase deficiency was discussed, because serum ammonia did not elevate in the ischemic exercise test.
 ...
PMID:[A 22-year-old man with long-standing weakness and atrophy predominantly in the lower extremities]. 879 13

We studied a 25-year-old man with paresis of the limbs and neck, scapular atrophy, facial weakness, exercise intolerance and frequent episodes of myoglobinuria. Muscle histochemistry and biochemistry revealed a combined defect of myophosphorylase and AMP deaminase. Molecular genetic analysis showed that the patient was homozygous for the two most common mutations associated with myophosphorylase and AMP deaminase deficiencies. This is the second documented case of genetic 'double trouble', which should be looked for in patients with unusual severe phenotypes.
 ...
PMID:Association of genetically proven deficiencies of myophosphorylase and AMP deaminase: a second case of 'double trouble'. 932 3