CLINICAL OUTCOME OF LONG-TERM MANAGEMENT OF PATIENTS WITH VITAMIN-B-12-UNRESPONSIVE METHYLMALONIC ACIDEMIA

We performed a retrospective study of all patients with methylmalonic acidemia diagnosed during the past 20 years. Only those patients who w ere nonresponsive to vitamin B-12 in vivo and in vitro were included. The final study group consisted of 26 patients, of whom 16 had a neona tal (early) onset; in 10 patients the diagnosis was made after 2 month s to 2.2 years (late onset). Of the early-onset patients, 14 (87%) die d, with a mean survival time of 1.5 years(range, 10 days to 2.5 years) , whereas four of the late-onset patients (40%) died (range, 1.2 to 15 years). At present, eight patients are alive; their mean age is 4.6 y ears (range, 1 to 10 years). In the early 1970s, treatment was based o n the principles of treating patients with phenylketonuria: restrictin g natural protein intake and supplementing essential amino acids, vita mins, and trace elements. After about 1980, nasogastric tube feeding b ecame a mainstay of the therapy, natural protein restriction became st ricter, and the use of essential amino acid mixtures diminished. Carni tine was added tg the therapy and, in later years, metronidazole. Sinc e these changes were implemented, the number of episodes of metabolic decompensation and hospitalizations has decreased. Mean survival time of the patients, in particular those with early onset, has only slight ly improved, partly because of psychosocial problems in many of these families. Almost all the patients', especially those with early onset, had some degree of neurologic impairment and mental retardation, and many patients were at less than 2 SD for weight or height or both. In contrast, the neurologic and mental status of the late-onset patients was frequently normal, and their weight and height were more often wit hin normal limits. Our results show that the treatment of methyl-malon ic acidemia still poses considerable problems; despite intense medical efforts and familial stress, the prognosis for the early-onset patien ts Is disappointing. The patients with late-onset disease, however, ap pear to have a fairly good prognosis with the present therapeutic appr oach. Liver transplantation or possibly genetic therapy might improve our results in the future.