Clinical Guidance

Hereditary fructose intolerance (HFI) typically manifests when fructose- and sucrose-containing foods are introduced in the course of weaning young infants from breast milk . Manifestations include nausea, bloating/ascites, vomiting, sweating, abdominal pain, enlarged liver, and growth retardation . Impaired gluconeogenesis following fructose ingestion results in acute hypoglycemia that is refractory to glucagon . Infants who ingest large quantities of fructose may develop lethargy, seizures, and/or progressive coma, or neonates given a 24% sucrose solution for analgesia during minor procedures may develop hypoglycemia leading to death. Presently, the clinical presentation of HFI can be multifaceted and nonspecific.

Diagnostic Criteria

No consensus clinical diagnostic criteria for hereditary fructose intolerance (HFI) have been published.

Suggestive Findings

HFI should be suspected in individuals with the following characteristic clinical findings (following dietary exposure to fructose, sucrose, sorbitol, and/or sucralose), metabolic disturbances, and family history. Note that the clinical presentation of HFI can be multifaceted and nonspecific, making it difficult to suspect based on clinical findings alone. If HFI is suspected, potential sources of fructose need to be removed immediately .

Management Guidelines

No clinical practice guidelines for hereditary fructose intolerance have been published. Note: If HFI is suspected, potential sources of fructose need to be removed immediately . Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with hereditary fructose intolerance (HFI), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 7. Recommended Evaluations Following Initial Diagnosis in Individuals with Hereditary Fructose Intolerance

Surveillance Guidelines

There are no formal guidelines for surveillance for individuals with HFI (e.g., frequency of subspecialty visits with physicians and/or dieticians with expertise in management of inherited metabolic diseases). Once the diagnosis of HFI has been made, periodic evaluation of liver function, renal function, and growth is reasonable, particularly if there are concerns regarding compliance with the fructose/sucrose/sorbitol/sucralose-restricted diet. Note: Isoelectric focusing of transferrin (or N-glycan evaluation by MS/MS) and/or monitoring of plasma lysosomal enzymes (aspartylglucosaminidase aspartylglucosaminidase and alpha-manosidase) may be elevated in untreated HFI, and thus, have been suggested as markers of disease control in HFI. None of these clinically available tests have definitively proven utility in diagnosis or surveillance [, , , , , ]. Table 10. Recommended Surveillance for Individuals with Hereditary Fructose Intolerance