Clinical Guidance

Because the numbers of individuals reported with molecularly confirmed epimerase deficiency galactosemia are currently limited, it is difficult to make strong genotype-phenotype correlations. However, some GALE variants have been associated with mild or severe outcomes in multiple affected individuals.

• Individuals who are homozygous for (p.Val94Met) are likely to have generalized epimerase deficiency galactosemia and have a more severe outcome .

• Individuals who have biallelic GALE alleles that are each associated with higher residual GALE activity in non-peripheral cells, such as (p.Lys257Arg) and (p.Gly319Glu), are more likely to have asymptomatic peripheral epimerase deficiency . However, too few individuals have been described to confirm or refute this prediction.

Source: GeneReviews — "Epimerase Deficiency Galactosemia"

Diagnostic Criteria

Epimerase deficiency galactosemia (GALE deficiency galactosemia) is a continuum comprising three forms:

• Generalized. Enzyme activity is profoundly decreased in all tissues tested.

• Peripheral. Enzyme activity is deficient in red blood cells (RBC) and circulating white blood cells, but normal or near normal in all other tissues.

• Intermediate. Enzyme activity is deficient in RBC and circulating white blood cells and less than 50% of normal levels in other cells tested.

Suggestive Findings

Epimerase deficiency galactosemia should be suspected in individuals with the following newborn screening results, suggestive clinical features, and supportive laboratory findings while on a normal milk diet.

Newborn screening results

Source: GeneReviews — "Epimerase Deficiency Galactosemia"

Differential Diagnosis

GALT deficiency. Galactosemia caused by deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT) may be divided into three clinical/biochemical phenotypes: (1) classic galactosemia; (2) clinical variant galactosemia; and (3) Duarte (biochemical variant) galactosemia. This categorization is based on: residual erythrocyte GALT enzyme activity; the levels of galactose metabolites (e.g., erythrocyte galactose-1-phosphate and urine galactitol) that are observed both off and on a lactose-restricted diet; and, most importantly, the likelihood that the affected individual will develop acute and chronic long-term complications. Biallelic pathogenic variants in GALT are causative; inheritance is autosomal recessive.

Source: GeneReviews — "Epimerase Deficiency Galactosemia"

Management Guidelines

When epimerase deficiency galactosemia is suspected during the diagnostic evaluation (for example, if total galactose is elevated on newborn screening results), initiation of a galactose/lactose-restricted diet should begin immediately . To the authors' knowledge, no clinical practice guidelines for epimerase deficiency galactosemia have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with epimerase deficiency galactosemia that is not clearly peripheral, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Epimerase Deficiency Galactosemia

Source: GeneReviews — "Epimerase Deficiency Galactosemia"

Clinical Guidance

Persons with generalized epimerase deficiency galactosemia should be on a galactose/lactose-restricted diet, certainly as infants and perhaps for life. Persons with intermediate epimerase deficiency galactosemia may be placed on a galactose/lactose-restricted diet, either transiently or long term. Assessment of hemolysate gal-1P and/or urinary galactitol following a galactose challenge (e.g., 2 weeks on a normal diet) may help determine if an individual should remain on a galactose/lactose-restricted diet for longer periods of time.

Source: GeneReviews — "Epimerase Deficiency Galactosemia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Epimerase Deficiency Galactosemia"

Surveillance Guidelines

Table 5. Recommended Surveillance for Individuals with Generalized or Intermediate Epimerase Deficiency Galactosemia

Source: GeneReviews — "Epimerase Deficiency Galactosemia"