Objective: To present two rare cases of RTD type 2 with co-existing AMP deaminase deficiency.

Background: RTD, formerly known as Brown-Vialetto-Van Laere syndrome, is a rare progressive neurological syndrome of early life featuring auditory and optic neuropathy, muscle weakness involving bulbar muscles and diaphragm and sensory ataxia (Allison T, 2017). Thus, it can mimic mitochondrial disease and may present to movement disorder neurologists because of ataxia. The diagnosis now can be made by detecting genetic mutations, particularly SLC52A3 and SLC52A2, responsible for the two main RTD types, type 3 and 2. Untreated patient usually die by around 9 years of age (Mah JK, 2017), but long-term survival into late adulthood has reported to treatment with high dose oral riboflavin (Jaeger B., 2016) – hence the importance of accurate diagnosis. AMP deaminase deficiency is also a condition with known genetic mutation (AMPD1) with a reported prevalence of 2% in early studies (Fishbein W. N., 1978, Morisaki T., 1986). However, acquired form in the presence of other neuromuscular conditions has also been identified (Fishbein W, 1985).

Method: Case report.

Results: We report two long-term survivors of RTD type 2 due to compound heterozygous 185 T>G and 1258G>A mutations in gene SLC 2A2. They are two brothers of a heavily affected family in which two female siblings died in childhood from a similar syndrome of visual impairment, ataxia and muscle weakness. Both brothers are unusual in that they have survived for much longer than expected despite a major delay from symptom onset to formal genetic diagnosis. Muscle biopsies in both showed AMP deaminase deficiency without AMPD1 mutation on whole genome sequencing.

Conclusion: Co-existing RTD type 2 and muscle AMP deaminase deficiency has not been previously reported. We hypothesise that the coexisting AMP deaminase deficiency may have helped in preserving muscle function and therefore survival through accumulation of AMP in muscle (Fabrice Rannou, et. al 2017). In our RTD family, the absence of a mutation in AMPD1 suggests an acquired AMP deaminase deficiency may result from compensatory downregulation in the setting of disturbed muscle energy metabolism. Future research such as examining the prevalence of AMP deaminase deficiency in the categories of muscle disease would be useful to test this hypothesis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/another-mitochondrial-disease-mimic-two-case-reports-of-adult-riboflavin-transporter-deficiency-rtd-type-2-with-muscle-adenosine-monophosphate-amp-deaminase-deficiency/