Clinical Guidance

In general, clinically relevant genotype-phenotype correlations have not been found .

Source: GeneReviews — "Barth Syndrome"

Diagnostic Criteria

For the purposes of this GeneReview, the terms "male" and "female" are narrowly defined as the individual's biological sex at birth as it determines clinical care . No consensus clinical diagnostic criteria for Barth syndrome have been published.

Suggestive Findings

Barth syndrome should be suspected in probands with the following clinical and supportive laboratory findings and family history. Clinical findings in infancy (age 0-12 months)

Source: GeneReviews — "Barth Syndrome"

Differential Diagnosis

Increased urinary excretion of the branched-chain organic acid 3-methylglutaconate (3-MGC) is a relatively common finding in children investigated for suspected inborn errors of metabolism. 3-MGC is an intermediate of leucine degradation and the mevalonate shunt pathway that links sterol synthesis with mitochondrial acetyl-coenzyme A metabolism. A classification of inborn errors of metabolism with 3-methylglutaconic aciduria (3-MGCA) as the discriminative feature was published by and . Clinical features and biochemical findings of syndromes associated with 3-MGCA vary. Tissues with higher requirements for oxidative metabolism, such as the central nervous system and cardiac and skeletal muscle, are predominantly affected. Cardiomyopathy. Left ventricular noncompaction (LVNC) is seen in other genetic syndromes as an isolated finding or associated with other congenital cardiac malformations. Other genes in which pathogenic variants can lead to isolated cardiomyopathy with left ventricular noncompaction include those listed in . Neutropenia. The differential diagnosis for isolated neutropenia is wide and includes several notable genetic conditions . Table 4. Barth Syndrome: Genetic Disorders of Interest in the Differential Diagnosis

Management Guidelines

No clinical practice guidelines for Barth syndrome 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 Barth syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Barth Syndrome: Recommended Evaluations Following Initial Diagnosis

Clinical Guidance

Avoid the following:

• Prolonged fasting because of a predisposition to hypoglycemia

• The use of rectal thermometers in those with neutropenia

• The use of succinylcholine, as nondepolarizing neuromuscular blockers could have a prolonged effect

The use of human growth hormone is not typically indicated, as most affected males will attain normal stature by adulthood. However, recommendations about use of human growth hormone may vary based on the testing and recommendations by specialists in endocrinology. Although the use of sevoflurane has been reported without adverse effects, the muscular involvement in Barth syndrome may increase the risk for malignant hyperthermia compared to the general population .

Source: GeneReviews — "Barth Syndrome"

Therapies Under Investigation

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

Source: GeneReviews — "Barth Syndrome"

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 9. Barth Syndrome: Recommended Surveillance

Source: GeneReviews — "Barth Syndrome"