Clinical Guidance

3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency presents with a wide spectrum of clinical features. HIBCH deficiency can be categorized into three subtypes based on age of presentation. Neonatal onset, the least frequent phenotype, is characterized by hypotonia, seizures, and feeding difficulties at birth. There is a high risk of death in childhood, and individuals that survive typically have developmental delay, seizures, poor weight gain, and growth deficiency and develop a movement disorder. Infantile onset is the most common phenotype, presenting in the first two years of life with feeding difficulties, vomiting, developmental delay with regression, hypotonia, seizures, movement disorder, microcephaly, vision impairment, and episodes of neurologic deterioration. Late onset is the second most common phenotype, presenting in childhood as a slowly progressive disease with significant movement disorder with or without paroxysmal dystonia, variable cognitive impairment, and high survivability. To date, 62 individuals have been identified with HIBCH deficiency [, , , , , , , , , , , , , , , , , , , , , , , , , , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. 3-Hydroxyisobutyryl-CoA Hydrolase Deficiency: Frequency of Select Features

Diagnostic Criteria

No consensus clinical diagnostic criteria for 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency have been published.

Suggestive Findings

HIBCH deficiency can be categorized into three subtypes based on age of presentation. Typically, earlier age of onset (e.g., neonatal onset) is associated with more severe disease. HIBCH deficiency should be suspected in probands with the following clinical, laboratory, and imaging findings and family history.

Clinical findings

• Neonatal onset (age 30 days)

Management Guidelines

No clinical practice guidelines for 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with HIBCH deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 7.

3-Hydroxyisobutyryl-CoA Hydrolase Deficiency: Recommended Surveillance

System/Concern | Evaluation | Frequency

Metabolic/