Clinical Guidance

Currently, no clear relationship exists between the type and position of the SERAC1 pathogenic variants and phenotype. The level of 3-methylglutaconic aciduria does not correlate with the clinical course.

Source: GeneReviews — "SERAC1 Deficiency"

Diagnostic Criteria

Suggestive Findings

SERAC1 deficiency should be suspected in an individual with: one of the three main defined within the SERAC1 deficiency spectrum; characteristic ; and autosomal recessive .

Three Main Clinical Phenotypes

1. Infantile, severe MEGD(H)EL syndrome (3-methylglutaconic aciduria with deafness-dystonia, [hepatopathy], encephalopathy, and Leigh-like syndrome):

Source: GeneReviews — "SERAC1 Deficiency"

Differential Diagnosis

Differential diagnosis of 3-methylglutaconic aciduria (3-MGA-uria). Increased urinary excretion of the branched-chain organic acid 3-MGA (3-MGA-uria) is a relatively common finding in children investigated for suspected inborn errors of metabolism . Inborn errors of metabolism with 3-MGA-uria as a discriminative feature show a characteristic "syndromal" pattern of signs and symptoms . The exact source of 3-MGA-uria is known only in AUH defect, the rarest type, caused by primary deficiency of the mitochondrial enzyme 3-methylglutaconyl-CoA hydratase resulting in blockage of leucine catabolism. The origin of the increased 3-MGA excretion in all other types is unknown, but mitochondrial dysfunction is thought to be the common denominator . Table 4. Genes of Interest in the Differential Diagnosis of SERAC1 Deficiency

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SERAC1 deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with SERAC1 Deficiency

Source: GeneReviews — "SERAC1 Deficiency"

Clinical Guidance

Medications known to impair mitochondrial function (e.g., valproic acid) should be avoided.

Source: GeneReviews — "SERAC1 Deficiency"

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 — "SERAC1 Deficiency"

Surveillance Guidelines

Table 7.

Recommended Surveillance for Individuals with SERAC1 Deficiency

System/Concern | Evaluation | Frequency

Feeding

| • Measurement of growth parameters

• Eval of nutritional status safety of oral intake

| At each visit

Respiratory

| Monitor for evidence of aspiration respiratory insufficiency.

Neurologic

| • Monitor those w/seizures as clinically indicated.

• Assess for new manifestations such as seizures, changes in tone, movement disorders.

Development

| • Monitor developmental progress incl possibility of cognitive decline.

• Monitor educational needs.

Musculoskeletal

| Physical medicine, OT/PT assessment of scoliosis, contractures, mobility, self-help skills

Hearing loss

| Monitor effectiveness of hearing aids possible need for alternative means of communication.

Optic atrophy

| Monitor vision.

Family/

Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources) care coordination.

Source: GeneReviews — "SERAC1 Deficiency"