1 - Serviço de Genética Médica, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
2 - CGPP - Centro de Genética Preditiva e Preventiva, IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal;
3 - I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;
4 - Serviço de Neuropediatria, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
5 - Unidade de Doenças Metabólicas, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
6 - Serviço de Neuropediatria, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal;
- Poster no 17th International Symposium da Sociedade Portuguesa de Doenças Metabólicas, Fátima, 8 a 10 de setembro de 2021
Resumo
INTRODUCTION: Primary mitochondrial disorders (PMD) are a complex group of diseases with challenging diagnosis arising from its nonspecific presentation and absence of reliable mitochondrial biomarkers. Mitochondrial Disease Criteria (MDC) using clinical, metabolic, imaging, and histopathologic features and biochemical investigations of skeletal muscle has been used for the diagnosis of PMD in infants and children prior to genetic testing or when mutation analysis is inconclusive. Nonetheless, it should be noted that many genetic disorders might present in a similar way, mimicking PMD. Aim: We present a cohort of three cases previously diagnosed as “probable PMD” according to consensus MDC, in which alternative primary diagnoses have recently been identified. CASE REPORTS: P1: An infant male presented with developmental delay, pyramidal and extrapyramidal signs, severe gastroesophageal reflux, failure to thrive, increased serum lactate, pyruvate and alanine, and decreased activity of pyruvate dehydrogenase complex. P2: A two-year-old female came to attention for developmental delay, microcephaly, strabismus, failure to thrive, recurrent prostration episodes and chronic vomiting, with elevated lactate and lactate/pyruvate ratio; MRI showed a cerebellar atrophy; respiratory chain studies in muscle biopsy revealed complex V and II+III deficiency. P3: A female with a 22q11.2 microdeletion presented with a severe rhabdomyolysis episode at age three. In recent years, she developed episodic weakness, epilepsy and hypothyroidism; muscle biopsy identified a complex II and IV deficiency. Recently, genomic evaluation revealed a non-mitochondrial diagnosis for each case: P1, Allan-Herndon-Dudley syndrome (SLC16A2, MIM#300523); P2, mental retardation and microcephaly with pontine and cerebellar hypoplasia (CASK, MIM#300749); P3, metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (TANGO2, MIM#616878). CONCLUSION: Recent advances in molecular diagnosis such as chromosomal microarray and next generation sequencing have shown that some patients with clinical and biochemical features suggestive of PMD may have other genetic disorder. When a PMD is suspected, genomic testing should be considered as first or second line test in the diagnostic workflow. urthermore, the recognition of mitochondrial mimics and establishment of an accurate diagnosis is important for patient management and genetic counselling