Alternative titles; symbols
ORPHA: 411712;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17p13.2 | Riboflavin deficiency | 615026 | Autosomal dominant | 3 | SLC52A1 | 607883 |
A number sign (#) is used with this entry because riboflavin deficiency (RBFVD) is caused by heterozygous mutation in the SLC52A1 gene (607883) on chromosome 17p13.
Chiong et al. (2007) reported a newborn who presented soon after birth with poor suck, hypoglycemia, and metabolic acidosis. She had dicarboxylic aciduria and elevated plasma acylcarnitine levels, initially thought to be consistent with multiple acyl-CoA dehydrogenase deficiency (MADD; 231680). Treatment with oral riboflavin resulted in complete resolution of the clinical and biochemical findings. Because of this rapid and compete response, maternal riboflavin deficiency was postulated and confirmed by serum testing. The mother reported severe vomiting and a restricted diet during pregnancy, but had no other signs or symptoms of riboflavin deficiency. While on a normal diet, the mother showed increased serum acylcarnitine levels, which normalized after riboflavin supplementation, suggesting that she had a primary deficiency in riboflavin metabolism. Riboflavin supplementation in the child was stopped at age 15 months, and she showed normal development. Primary MADD deficiency in the child was excluded by genetic analysis. The findings were consistent with transient neonatal riboflavin deficiency secondary to maternal riboflavin deficiency that was exacerbated during pregnancy. Ho et al. (2011) reported follow-up of the family reported by Chiong et al. (2007) and noted that the mother had a second unaffected child while taking oral riboflavin supplementation during pregnancy.
Mosegaard et al. (2017) reported a female infant, conceived by in vitro fertility treatment with an anonymous sperm donor, with transient neonatal riboflavin deficiency. The patient's mother had experienced hyperemesis gravidarum and lost 20 kg during the pregnancy, but had no apparent signs or symptoms of riboflavin deficiency (sore mucous membranes, photophobia, or dermatitis). The infant presented at 4 days of age with lethargy, hypotonia, poor peripheral circulation, hypothermia, and metabolic lactic acidosis. Her acylcarnitine profile suggested a diagnosis of MADD. Following treatment with hemofiltration and riboflavin, repeat newborn screening analysis at 8 and 10 days of age showed acylcarnitines in the reference range and a nearly normal level of plasma acylcarnitines. Riboflavin levels in the mother's whole blood were at the lower limit of normal. Riboflavin levels could not be measured in the infant due to the transfusion. Riboflavin treatment was continued for 30 months, and carnitine substitution for 12 months. The child showed normal psychomotor development at age 3 years.
In a woman with riboflavin deficiency who had an infant with transient neonatal riboflavin deficiency (Chiong et al., 2007), Ho et al. (2011) identified a de novo heterozygous 1.9-kb deletion in the SLC52A1 gene (607883.0001), predicted to result in haploinsufficiency. The infant did not carry the deletion. These findings confirmed that the transient clinical and metabolic abnormalities in the infant were the result of maternal riboflavin deficiency.
In an infant with neonatal riboflavin deficiency, Mosegaard et al. (2017) identified heterozygosity for an intronic mutation in the SLC52A1 gene (607883.0002). The patient's unaffected mother was also heterozygous for the mutation. The father was not available for study.
Chiong, M. A., Sim, K. G., Carpenter, K., Rhead, W., Ho, G., Olsen, R. K. J., Christodoulou, J. Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency. Molec. Genet. Metab. 92: 109-114, 2007. [PubMed: 17689999] [Full Text: https://doi.org/10.1016/j.ymgme.2007.06.017]
Ho, G., Yonezawa, A., Masuda, S., Inui, K., Sim, K. G., Carpenter, K., Olsen, R. K. J., Mitchell, J. J., Rhead, W. J., Peters, G., Christodoulou, J. Maternal riboflavin deficiency, resulting in transient neonatal-onset glutaric aciduria type 2, is caused by a microdeletion in the riboflavin transporter gene GPR172B. Hum. Mutat. 32: E1976-E1984, 2011. Note: Electronic Article. [PubMed: 21089064] [Full Text: https://doi.org/10.1002/humu.21399]
Mosegaard, S., Bruun, G. H,, Flyvbjerg, K. F., Bliksrud, Y. T., Gregersen, N., Dembic, M., Annexstad, E., Tangeraas, T., Olsen, R. K. J., Andresen, B. S. An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Molec. Genet. Metab. 122: 182-188, 2017. [PubMed: 29122468] [Full Text: https://doi.org/10.1016/j.ymgme.2017.10.014]