Clinical Guidance

Because most pathogenic variants are private, genotype/phenotype correlations are difficult. Of note, the phenotypes were indistinguishable in the five individuals with the recurrent SKIC3 variant (Trp936Ter) and those with other SKIC3 pathogenic variants .

Source: GeneReviews — "Trichohepatoenteric Syndrome"

Diagnostic Criteria

To date, no diagnostic algorithm for trichohepatoenteric syndrome (THES) has been published.

Suggestive Findings

THES should be suspected in individuals with the following clinical findings :

Source: GeneReviews — "Trichohepatoenteric Syndrome"

Differential Diagnosis

Table 3. Monogenic Disorders with Intractable Diarrhea to Consider in the Differential Diagnosis of Trichohepatoenteric Syndrome

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with trichohepatoenteric syndrome (THES), the following evaluations are recommended:

• Nutritional evaluation by a specialist pediatric nutritionist

• Immunologic assessment with serum IgG, IgM, IgA; immunophenotyping; if immunization has been performed before, evaluation of the level of specific antibodies to detect a rapid loss of protective antibodies, which would require immunoglobulin supplementation

• Liver assessment: ultrasound evaluation; assessment of liver enzymes (ALT/AST, GGT); in case of abnormalities, consult a pediatric hepatologist for recommendations on additional investigations

• Cardiac evaluation for congenital malformations

• Age-appropriate assessment of cognitive development, speech and language development, and psychosocial skills

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

No specific treatment is available. The goals of the treatment are to promote maximal weight gain and linear growth, to reduce the burden of infections, and to provide individual management of intellectual disability. Weight gain. Most children, when first diagnosed, require parenteral nutrition (PN) to achieve appropriate weight gain and catch-up growth. Although PN is usually required, it can be combined (as tolerated) with oral feeding – typically a semi-elemental diet .

Source: GeneReviews — "Trichohepatoenteric Syndrome"

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 — "Trichohepatoenteric Syndrome"

Surveillance Guidelines

Although there are no consensus guidelines, the following surveillance is recommended:

• For children not receiving parenteral nutrition, close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention should nutritional deficiency become a concern

• Yearly assessment of the following main features:

• Diarrhea. If the nature of the diarrhea changes (e.g., appearance of bloody diarrhea), investigation of possible inflammatory bowel disease (IBD) is warranted .

• Liver function. Ultrasound examination and measurement of liver enzymes (AST, ALT, GGT), International Normalized Ratio (INR), and bilirubin

• Serum concentration of IgG, IgM, IgA, and immunoglobulin functionality (i.e., immunophenotyping) even if results at the time of initial evaluation were normal. Consultation with an immunologist is warranted if immunoglobulin levels are low or if normal immunoglobulin levels are associated with a loss of specific protective antibody.

• TSH level for evidence of hypothyroidism

• Assessment of cognitive development, speech and language, and psychosocial skills for evidence of intellectual disability at ages 2, 4, 8, 12, and 15 years unless concerns appear earlier

• As evolution of the dermatologic features (mostly hypo- or hyperpigmented patches and hair abnormalities) is unknown, regular evaluation by a dermatologist seems reasonable.

Source: GeneReviews — "Trichohepatoenteric Syndrome"