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De levensverwachting van personen met trisomie 21 is spectaculair toegenomen. Meer volwassenen leven langer. De opvolging van kinderen met trisomie 21 gebeurt op systematische en gecoordineerde manier om op gezondheidsproblemen te anticiperen en tijdig te herkennen. Dat is bij volwassenen minder het geval. Gecoordineerde, systematische opvolging van de gezondheid van volwassenen met trisomie 21 wordt wel in de literatuur aanbevolen en kan een belangrijke impact hebben op de gezondheidstoestand en kwaliteit van leven. De huisarts bekleedt een ideale positie om deze zorg te coordineren. Deze bijdrage geeft een beknopt overzicht van de verschillende gezondheidsproblemen en een stelt een schema voor opvolging voor.

Over the last decade, many sporadic and familial cases have been reported with multiple deletions of mitochondrial DNA (mtDNA) in postmitotic tissues. Most patients suffer from progressive external ophthalmoplegia (PEO) and may have a nuclear gene defect that predisposes to the accumulation of mtDNA deletions. Recently, positional cloning has led to the discovery of mutations in four such nuclear genes. Some mutations are dominant and others recessive. In all autosomal mutations, defective mtDNA replication and/or repair are probably responsible for the generation of secondary mtDNA deletions. There are also data suggestive of a prominent pathogenic role for disturbed nucleotide metabolism. We here present a tentative genotype-phenotype correlation. Since clinical presentations are heterogeneous and overlap with different previously described clinical syndromes, we advocate the use of a genetic, instead of a clinical, classification of disorders with multiple mtDNA deletions.

Autosomal recessive progressive external ophthalmoplegia (PEO) is one clinical disorder associated with multiple mitochondrial DNA deletions and can be caused by missense mutations in POLG, the gene encoding the mitochondrial DNA polymerase gamma. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is another autosomal recessive disorder associated with PEO and multiple deletions of mitochondrial DNA in skeletal muscle. In several patients this disorder is caused by loss of function mutations in the gene encoding thymidine phosphorylase (TP). We report a recessive family with features of MNGIE but no leukoencephalopathy in which two patients carry three missense mutations in POLG, of which two are novel mutations (N846S and P587L). The third mutation was previously reported as a recessive POLG mutation (T251I). This finding indicates the need for POLG sequencing in patients with features of MNGIE without TP mutations.