[Severe lactic acidosis requiring continuos haemodiafiltration in a young patient with unrecognized metabolic abnormality. Case report].

BACKGROUND: Lactic acidosis (LA) is the most common form of metabolic acidosis, defined by lactate values greater than 5 mmol/L and pH<7.34. The pathogenesis of LA involves hypoxic causes (type A) and non-hypoxic (type B), often coexisting. Identification and removal of the trigger are mandatory in the therapeutic management of LA. The case: A 38 years-old male patient entered the Emergency Ward for dyspnea, fever, vomiting and hyporexia. An important respiratory distress with hyperventilation due to severe LA was found, together with severe hypoglicemia, without renal impairment. Past medical history unremarkable, except for reported episodic hypoglicemia in the childhood, with fructose "intolerance", without any other data. No evidence of intoxications, septic shock or significant cytolysis. No drugs causing LA. The patient underwent orotracheal intubation, glucose infusion, and continuous haemodiafiltration for 36-hrs. A rapid general improvement was obtained with stabilization of acid-base balance. A diagnosis of fructose-1,6-diphosphatase deficiency was made. It is an autosomical recessive gluconeogenesis abnormality, with recurrent episodes of hypoglicemia and lactic acidosis after fasting, potentially lethal. The therapy is based on avoiding prolonged fasts, glucose infusion, and a specific diet, rich in glucose without fructose intake. CONCLUSIONS: The presence of not-otherwise-explained lactic acidosis in young patients has to place the suspect of an underlying and unknown metabolic derangement; in these cases, the involvement of the nephrologist appears to be pivotal for the differential diagnosis of the abnormalities of the acid-base balance, and for setting the best treatment.

International practices in the dietary management of fructose 1-6 biphosphatase deficiency.

BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. CONCLUSIONS: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.

Gluconeogenesis defect presenting with resistant hyperglycemia and acidosis mimicking diabetic ketoacidosis.

Fructose-1,6-diphosphatase (FDPase) enzyme deficiency is a rare inherited metabolic disease. Affected patients usually present with metabolic crisis including hypoglycemia, acidosis, ketonuria, and hyperuricemia. A previously healthy 8-month-old male infant presented with fever, vomiting, and hypoactivity. He had tachycardia, tachypnea, and a tendency to sleep. The patient had signs of severe dehydration and shock. Laboratory findings revealed significant lactic acidosis, hyperuricemia, hyperglycemia, elevated liver enzyme level, and hyperlipidemia. The urine analysis had evidence of glycosuria and ketonuria. Hyperuricemia, lactic acidemia, and hyperglycemia persisted despite insulin infusion, adequate hydration, and perfusion. Consequently, peritoneal dialysis was started. About 12 hours after dialysis, his metabolic derangements were normalized, and clinical status was improved dramatically. His metabolic disease workup was compatible with FDPase deficiency. Here, we described a metabolic attack of FDPase deficiency presented with hyperglycemia mimicking diabetic ketoacidosis.

Three successful pregnancies through dietary management of fructose-1,6-bisphosphatase deficiency.

Fructose-1,6-bisphosphatase (FBPase) deficiency (OMIM 229700) has been characterized as the cause of life-threatening hypoglycaemia and lactic acidaemia following prolonged fasting. The patient, an adult African-American woman, presented during the second trimester of her first pregnancy with recurrent episodes of lactic acidaemia and hypoglycaemia. She had recently been admitted to a nearby intensive care unit after presentation with profound hypoglycaemia and lactic acidosis, and was found to be pregnant. The history was remarkable for approximately 30 hospitalizations for hypoglycaemia and acidosis. She had previously undergone liver biopsy at another centre and was diagnosed with a 'glycogen storage disease', although no enzyme testing had been done for confirmation. Based on clinical symptoms, a diagnosis of FBPase deficiency was accomplished through gene sequencing, which revealed homozygosity for a panethnic, common mutation, 960/961insG in exon 7. The availability of mutation testing facilitated the confirmation of FBPase deficiency in this patient, obviating liver biopsy for enzyme activity confirmation. The patient underwent three successful pregnancies by strict compliance with dietary management, including nocturnal uncooked cornstarch to manage hypoglycaemia. The pregnancies were complicated by mild gestational diabetes, increased cornstarch requirements, and hypoglycaemia at the time of discharge from the hospital. The three infants had normal birth weights and experienced no complications during the neonatal period. The patient subsequently developed sensorineural hearing loss and early-onset cognitive impairment, despite compliance with the monitoring and treatment of hypoglycaemia. The experience with multiple pregnancies in this FBPase-deficient patient provides insight into the management of hypoglycaemia in inherited disorders of gluconeogenesis.