[Private mutations in the myophosphorylase gene: the first case in a patient of Latin American descent]. / Mutaciones privadas en el gen de la miofosforilasa: primer caso en un paciente de origen latinoamericano.

INTRODUCTION: McArdle's disease (glycogenoses type V) is a common metabolic myopathy caused by deficient myophosphorylase activity. The disease is due to mutations in the myophosphorylase (PYGM) gene and is present in a large number of countries. CASE REPORT: A 13-year-old male who suffered an episode of muscle pain and offered increased levels of creatinkinase in plasma, myoglobinuria and mild weakness of the proximal muscles, after short but vigorous exercise. The patient was born in Ecuador and was adopted by a Spanish family. The myophosphorylase gene was analysed completely and the patient was found to be a carrier of a missense mutation, a homozygous change where a G is replaced by an A in exon 11, changing a valine for a methionine in codon 456 (V456M). The mutation described above affects an amino acid that is conserved in the enzyme and which was not present in the control population that was studied. CONCLUSIONS: These findings show the presence of McArdle's disease in several ethnic groups and confirm that the ethnic origin of the patient is important when it comes to deciding what mutations should be analysed first in molecular diagnosis studies.

Mutaciones privadas en el gen de la miofosforilasa: primer caso en un paciente de origen latinoamericano / Private mutations in the myophosphorylase gene: The first case in a patient of latin american descent

La enfermedad de McArdle (glicogenosis tipo V) es una miopatía metabólica común causada por unadeficiencia de la actividad de la miofosforilasa. La enfermedad se debe a mutaciones en el gen de la miofosforilasa (PYGM) y está presente en un gran número de países. Caso clínico. Varón de 13 años de edad que sufrió un episodio de dolor muscular y presentó unos niveles elevados de creatincinasa en plasma, mioglobinuria y debilidad de la musculatura proximal moderada, después de un corto pero vigoroso ejercicio. El paciente nació en Ecuador y fue adoptado por una familia española.Se analizó completamente el gen de la miofosforilasa y se encontró que el paciente era portador de una mutación consistente en pérdida de sentido, un cambio homocigótico de una G por una A en el exón 11, cambiando una valina por una metionina en el codón 456 (V456M). La mutación previamente descrita afecta a un aminoácido conservado en la enzima y no estaba presenteen la población control estudiada. Conclusiones. Estos hallazgos demuestran la presencia de la enfermedad de McArdle en varios grupos étnicos y sugiere que el origen étnico del paciente es importante para decidir qué mutaciones deberían analizarse primero en los estudios diagnósticos moleculares (AU)

McArdle's disease (glycogenoses type V) is a common metabolic myopathy caused by deficientmyophosphorylase activity. The disease is due to mutations in the myophosphorylase (PYGM) gene and is present in a large number of countries. Case report. A 13-year-old male who suffered an episode of muscle pain and offered increased levels of creatinkinase in plasma, myoglobinuria and mild weakness of the proximal muscles, after short but vigorous exercise. The patient was born in Ecuador and was adopted by a Spanish family. The myophosphorylase gene was analysed completely andthe patient was found to be a carrier of a missense mutation, a homozygous change where a G is replaced by an A in exon 11, changing a valine for a methionine in codon 456 (V456M). The mutation described above affects an amino acid that is conserved in the enzyme and which was not present in the control population that was studied. Conclusions. These findings show thepresence of McArdle’s disease in several ethnic groups and confirm that the ethnic origin of the patient is important when it comes to deciding what mutations should be analysed first in molecular diagnosis studies (AU)

Familial amyloidosis in a large Spanish kindred resulting from a D38V mutation in the transthyretin gene.

BACKGROUND: Transthyretin amyloidosis, also known as familial amyloidotic polyneuropathy, is an autosomal dominant disorder that results from a mutation in the gene encoding plasma transthyretin (TTR). Distinct clinical presentations of the disease have been related so far to different point mutations, polyneuropathy being the predominant clinical feature in the majority of cases. Nevertheless, misdiagnosis of familial forms of amyloidosis is still common. MATERIALS AND METHODS: A 71-year-old man was admitted to our hospital for heart failure. He had been previously diagnosed of AL amyloidosis with predominant polyneuropathic, cardiac and laryngeal involvement on the basis of clinical data and amyloid deposition in tissue specimens. During admission, suspicion of transthyretin amyloidosis was raised due to the absence of renal involvement, monoclonal protein and plasma cell dyscrasia. Complete clinical evaluation and sequence analysis of the TTR gene of the patient and his family were performed. RESULTS: Gene sequence analysis revealed a rare A-to-T transition in exon 2 resulting in the substitution of aspartic acid by valine at position 38 (D38V) in the index case and in two other members of the family. Clinical study of the kindred showed a predominant late-onset heart involvement with variable polyneuropathy. CONCLUSIONS: Here we report a large pedigree from Spain with three members affected by a severe late-onset form of amyloidosis due to a rare D38V TTR mutation. The variations on the natural history of this form of amyloidosis may have important consequences on genetic counselling, follow-up, and therapeutic approaches for these patients.

Variable presentation of the clinical phenotype of McArdle's disease in a kindred harbouring a novel compound genotype in the muscle glycogen phosphorylase gene.

We report a Spanish family with muscle glycogen phosphorylase (PYGM) deficiency (McArdle's disease) harbouring a novel compound genotype (A659D/L586P). Four individuals who had the same genotype for PYGM, showed a wide variability in the presentation of the clinical phenotype, including one patient with a restrictive respiratory pattern, which is unusual in McArdle's disease. Moreover, these patients were studied for the insertion/deletion (I/D) trait in the angiotensin converting enzyme (ACE) which has been suggested to be a strong modulator of severity in McArdle's disease. Our results indicate no association of the I/D ACE trait in this family, suggesting that other factors would be more relevant in determining the severity of the clinical presentation.