1452
be possible in this case to increase the sensitivity by further rounds of amplification. Schwartz et al correctly point out that this procedure allows a large number of mutations for various genetic diseases to be tested with a single Guthrie card but an even greater advantage of this procedure is that it eliminates the need for tedious and timeconsuming methods for extracting DNA from individual blood spots. Hence this procedure greatly reduces the time and complexity of PCR analysis of Guthrie blood spots, thus increasing the number of samples that can conveniently be handled, and thereby increasing the feasibility of large scale screening for genetic
diseases. PAUL V. NELSON WILLIAM F. CAREY C. PHILLIP MORRIS
Department of Chemical Pathology, Adelaide Children’s Hospital, South Australia 5006
1. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 248: 1073-80.
Mitochondrial mutation in fatal infantile
cardiomyopathy SIR,-Patients with myoclonus epilepsy associated with ragged-red fibres have an A-to-G transition in mitochondrial DNA (mtDNA). The mutation alters the structure of the transfer RNA molecule that transmits the instructions for lysine synthesis; as a result, mitochondrial protein synthesis is affected, leading to a bioenergetic dysfunction. We have identified a similar mutation in a patient with fatal infantile cardiomyopathy associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS type). A 1-year-old boy
was admitted to hospital because of general weakness. He was an only child of non-consanguineous healthy parents. Chest radiography revealed severe cardiomegaly. A lumbar tap was attempted, but was accompanied by cardiac arrest. After 10 min resuscitation, consciousness returned. The boy had anaemia, metabolic acidosis, and increased transaminase, lactate dehydrogenase, and creatine kinase activities. An electrocardiogram revealed premature ventricular contraction. Bradycardia developed with convulsions and the boy died from cardiac failure on the 7th hospital day. Severe dilatation and hypertrophy of the left ventricle was found at necropsy. The heart weighed 145 g (normal control 42 g) and was not infiltrated with inflammatory cells. Individual myocardial cells were swollen. The brain, liver, and lungs showed changes associated with congestive heart failure. There was individual cell necrosis and basophilic degeneration in the skeletal muscle. The kidneys contained several acidophilic casts, especially in the distal convoluted tubules, consistent with rhabdomyolysis.
Normal
Cardtomyopathy tRNA"’
tRNA"
A-lie C
A-Ile C
A A=U Aminoacyl G--_C C acceptor stem A=U A=U A=U A U=A TljlCloop A=U C-o
be possible in this case to increase the sensitivity by further rounds of amplification. Schwartz et al correctly point out that this procedure allows a large number of mutations for various genetic diseases to be tested with a single Guthrie card but an even greater advantage of this procedure is that it eliminates the need for tedious and timeconsuming methods for extracting DNA from individual blood spots. Hence this procedure greatly reduces the time and complexity of PCR analysis of Guthrie blood spots, thus increasing the number of samples that can conveniently be handled, and thereby increasing the feasibility of large scale screening for genetic
diseases. PAUL V. NELSON WILLIAM F. CAREY C. PHILLIP MORRIS
Department of Chemical Pathology, Adelaide Children’s Hospital, South Australia 5006
1. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science 1989; 248: 1073-80.
Mitochondrial mutation in fatal infantile
cardiomyopathy SIR,-Patients with myoclonus epilepsy associated with ragged-red fibres have an A-to-G transition in mitochondrial DNA (mtDNA). The mutation alters the structure of the transfer RNA molecule that transmits the instructions for lysine synthesis; as a result, mitochondrial protein synthesis is affected, leading to a bioenergetic dysfunction. We have identified a similar mutation in a patient with fatal infantile cardiomyopathy associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS type). A 1-year-old boy
was admitted to hospital because of general weakness. He was an only child of non-consanguineous healthy parents. Chest radiography revealed severe cardiomegaly. A lumbar tap was attempted, but was accompanied by cardiac arrest. After 10 min resuscitation, consciousness returned. The boy had anaemia, metabolic acidosis, and increased transaminase, lactate dehydrogenase, and creatine kinase activities. An electrocardiogram revealed premature ventricular contraction. Bradycardia developed with convulsions and the boy died from cardiac failure on the 7th hospital day. Severe dilatation and hypertrophy of the left ventricle was found at necropsy. The heart weighed 145 g (normal control 42 g) and was not infiltrated with inflammatory cells. Individual myocardial cells were swollen. The brain, liver, and lungs showed changes associated with congestive heart failure. There was individual cell necrosis and basophilic degeneration in the skeletal muscle. The kidneys contained several acidophilic casts, especially in the distal convoluted tubules, consistent with rhabdomyolysis.
Normal
Cardtomyopathy tRNA"’
tRNA"
A-lie C
A-Ile C
A A=U Aminoacyl G--_C C acceptor stem A=U A=U A=U A U=A TljlCloop A=U C-o
