Clinical Guidance

All affected individuals with the paroxysmal dystonia phenotype have been compound heterozygous for the pathogenic variant and a second pathogenic variant . The c.518CT variant, however, has not been identified in affected individuals with other, more severe clinical phenotypes .

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"

Diagnostic Criteria

No consensus clinical diagnostic criteria for ECHS1 deficiency (ECHS1D) have been published.

Suggestive Findings

Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D) should be suspected in individuals with clinical features of Leigh syndrome and/or exercise-induced dystonia who have supportive brain MRI and biochemical findings, including early-onset lactic acidosis.

Clinical features

• Neurologic

• Developmental delay, often severe [, , , ]

• Infantile encephalopathy (may be epileptic), hypotonia, and/or spasticity [, , , ]

• Dystonia (exercise induced) and/or choreoathetotic movements

• Growth. Failure to thrive, which may present prenatally as intrauterine growth restriction and/or oligohydramnios in the most severe cases

• Cardiorespiratory

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"

Differential Diagnosis

Table 3. Disorders to Consider in the Differential Diagnosis of ECHS1 Deficiency (ECHS1D)

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1D), the evaluations summarized (if they have not already been completed) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with ECHS1 Deficiency

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"

Clinical Guidance

Mitochondrial toxins, such as valproic acid and prolonged propofol infusions, should be avoided . The ketogenic diet may be poorly tolerated because of partially impaired fatty acid oxidation ; one preliminary report suggests rapid disease progression following initiation of the ketogenic diet and in two other affected individuals, subjects perished within days of starting a ketogenic diet . Therefore, ketogenic diet may not be effective to control lactic acidosis and may be harmful or even lethal – and thus should be avoided.

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 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 — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with ECHS1 Deficiency

Source: GeneReviews — "Mitochondrial Short-Chain Enoyl-CoA Hydratase 1 Deficiency"