A Chinese Adult Patient with Fructose 1,6-bisphosphatase Deficiency.

To the Editor: Fructose 1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive metabolic disease, which is characterized by episodic attacks of hypoglycemia, ketosis, and lactic acidosis triggered by long-term fasting or fever or plenty of a load of fructose.[1] As we all know, mutations of the fructose-1,6-bisphosphatase 1 gene (FBP1) could lead to FBPase deficiency which will correspondingly cause an enzymatic block in the last steps of the gluconeogenesis.[1] It is known to be often lethal during the neonatal period and infancy because of lack of storage of glycogen, however, there were also few reports of adult patients with this inherited disease. Here, we described a Chinese female adult with FBPase deficiency.

A 23-year-old woman first visited a local hospital because of vomiting, abdominal pain concomitant with fatigue and dizziness for 3 days. The laboratory findings showed that the white blood cell (WBC) count was 30.3 × 109/L, neutrophil (NEUT) count was 27.3 × 109/L, C-reactive protein was 48.3 mg/L, glucose (Glu) <0.6 mmol/L, and serum aspartate aminotransferase (AST) 325 U/L, and alanine aminotransferase (ALT) 194 U/L. The patient received some symptomatic therapy such as an infusion of glucose and administration of proton pump inhibitors, but her abdominal pain did not relieve so she was admitted to our emergency department one day later. Her further laboratory results showed HCO3− 4.7 mmol/L, anion gap (AG) 29.3 mmol/L, blood pH 7.00, Glu 3.90 mmol/L, K+ 6.0 mmol/L, serum lactate level 18.1 mmol/L, ALT 261 U/L, AST 313 U/L, triglyceride 19.9 mmol/L, serum phosphate level 1.4 mmol/L, cholesterol 7.8 mmol/L, uric acid 948.3 μmol/L, Urea 7.9 mmol/L, serum creatinine 112.0 μmol/L, urine ketone (U-KET) 1+, WBC 33.9 × 109/L, NEUT 30.1 × 109/L, indicating severe lactic acidosis, hypoglycemia, liver and kidney dysfunction, hyperlipidemia, and highly suspected infection. The patient was treated with intravenous glucose, bicarbonate, antibiotics, and other conservative therapy. The next day, she was transferred to our intense care unit and received previous treatment. Two days later, her ALT and AST were 88 U/L and 28 U/L, respectively, and her other biochemical indexes almost returned to normal level (serum lactate level 2.8 mmol/L, AG 13.7 mmol/L, Glu 4.5 mmol/L, K+ 3.7 mmol/L) four days later. All her uncomfortable symptoms disappeared, and she discharged after being hospitalized for 8 days.

The patient was well developed in body and intelligence. She suffered four episodes of acidosis and minor-epilepsy before one year old and recurrent of vomiting and fatigue had happened in the past. This acute event happened after she ate some mulberry which might be rich in fructose or might be insanitary. Many inherited endocrine and metabolism-related diseases could cause similar manifestations. We ruled out Type I glycogen storage disease first because no abnormality in her body growth or intelligence development and no hepatomegaly could be seen. Then, we excluded classical mitochondrial disease without evidence of the involvement of her nervous system, muscle or heart, and her mother was completely healthy. Considering the history and this attack, we speculated a possibility of FBPase deficiency. The FBP1 analysis revealed a G residue duplication at base 960 [c.960dupG, pSer321Valfs*13, Figure 1], which was in homozygous state in this patient and in heterozygous state both in her parents who were not consanguinity but lived in the same small village. This mutation, which is the most frequent one of the FBPase deficiencies in the Asian population, could result in a frame shift from codon 321 and premature termination at position 333 in exon 5.[2]

Figure 1

The duplication (c.960dupG, pSer321Valfs*13) identified in the patient with fructose 1,6-bisphosphatase deficiency. (a) Wild type; (b) Heterozygous mutation of c.960dupG; (c) Homozygous mutation of c.960dupG.

Effective treatment for this disease is taking adequate glucose or starch and avoiding long-time fasting or large intake of fructose. Most of the patients with FBPase deficiency have a good prognosis, and the tolerance of fasting might generally improve with age.[3]

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

The study was supported by a grant from the National Natural Scientific Foundation of China (No. 81170653).

Conflicts of interest

There are no conflicts of interest.