ABSTRACT
BACKGROUND: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder caused by mutation of the SLC2A2 gene, which encodes glucose transporter protein 2 (GLUT2). CASE SUMMARY: We report a 7-mo-old girl with cytomegalovirus infection presenting hepatomegaly, jaundice, liver transaminase elevation, fasting hypoglycemia, hyperglycosuria, proteinuria, hypophosphatemia, rickets, and growth retardation. After prescription of ganciclovir, the levels of bilirubin and alanine aminotransferase decreased to normal, while she still had aggravating hepatomegaly and severe hyperglycosuria. Then, whole exome sequencing was conducted and revealed a homozygous c.416delC mutation in exon 4 of SLC2A2 inherited from her parents, which was predicted to change alanine 139 to valine (p.A139Vfs*3), indicating a diagnosis of FBS. During the follow-up, the entire laboratory test returned to normal with extra supplement of vitamin D and corn starch. Her weight increased to normal range at 3 years old without hepatomegaly. However, she still had short stature. Although there was heterogeneity between phenotype and genotype, Chinese children had typical clinical manifestations. No hot spot mutation or association between severity and mutations was found, but nonsense and missense mutations were more common. Data of long-term follow-up were rare, leading to insufficient assessment of the prognosis in Chinese children. CONCLUSION: FBS is a rare genetic metabolic disease causing impaired glucose liver homeostasis and proximal renal tubular dysfunction. Results of urine and blood testing suggesting abnormal glucose metabolism could be the clues for FBS in neonates and infants. Genetic sequencing is indispensable for diagnosis. Since the diversity of disease severity, early identification and long-term follow-up could help improve patients' quality of life and decrease mortality.
ABSTRACT
Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterised by impaired glucose liver homeostasis and proximal renal tubular dysfunction. It is caused by pathogenic variants in SLC2A2 coding for the glucose transporter GLUT2. Main clinical features include hepatomegaly, fasting hypoglycaemia, postprandial hyperglycaemia, Fanconi-type tubulopathy occasionally with rickets, and a severe growth disorder. While treatment for renal tubular dysfunction is well established, data regarding optimal nutritional therapy are scarce. Similarly, detailed clinical evaluation of treated FBS patients is lacking. These unmet needs were an incentive to conduct the present pilot study. We present clinical findings, laboratory parameters and molecular genetic data on 11 FBS patients with emphasis on clinical outcome under various nutritional interventions. At diagnosis, the patients' phenotypic severity could be classified into two categories: a first group with severe growth failure and rickets, and a second group with milder signs and symptoms. Three patients were diagnosed early and treated because of family history. All patients exhibited massive glucosuria at diagnosis and some in both groups had fasting hypoglycaemic episodes. Growth retardation improved drastically in all five patients treated by intensive nutritional intervention (nocturnal enteral nutrition) and uncooked cornstarch with final growth parameters in the normal range. The four severely affected patients who were treated with uncooked cornstarch alone did not catch up growth. All patients received electrolytes and l-carnitine supplementation to compensate for the tubulopathy. This is one of the largest series of FBS on therapeutic management with evidence that nocturnal enteral nutrition rescues growth failure.