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Background Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder with heterogeneous phenotypic spectrum resulting from disease-causing variants in the dopa decarboxylase (DDC) gene. Consensus guidelines recommend dopamine agonists, monoamine oxidase inhibitors, and other symptomatic treatments, but most patients have an unrelenting disease course with no response to these therapies. Case presentation We describe 2 African American siblings with AADC deficiency and identify 2 DDC gene variants not previously associated with the disorder. The patients were evaluated for cognitive and neurologic impairments. Diagnosis of AADC deficiency was initially based on evaluation of urine and plasma metabolites, followed by targeted DDC gene sequencing. The first patient, a firstborn African American female, had moderate elevations of vanillactic and vanilpyruvic acids, and slight elevation of N-acetylvanilalanine in urine. The second patient, an African American female and younger sibling of the first patient, had low AADC enzyme activity and elevated 3-O-methyldopa levels in plasma. Genetic testing confirmed that both siblings possessed the same 2 DDC gene variants, which were identified as NM_000790.3: c.48C > A (p.Tyr16Ter) and NM_000790.3: c.116G > C (p.Arg39Pro). Conclusions This report describes 2 previously unknown patients with AADC deficiency and confirmed the presence of 2 DDC gene variants not previously associated with this disorder. Further research is needed to identify disease-modifying treatments for this devastating neurometabolic disorder. Gene therapy with a recombinant adeno-associated viral vector serotype 2 carrying the gene for the human AADC protein (AAV2-hAADC) is currently in clinical development.

This report describes a case of hypoplastic left heart syndrome (HLHS) and Marfan syndrome presenting in conjunction, and highlights how a connective tissue disorder may alter medical and surgical management of newborns with HLHS.

We present an unusual case of unconjugated hyperbilirubinemia in a 6 day old infant. The bilirubin peaked at 20.1/ 0.6 mg/dL. A work-up for a hemolytic process or metabolic disorder was negative. Crigler-Najjar was suspected. Phenobarbital was given for 3 days with no significant change in bilirubin level. He was discharged home after 20 days of phototherapy with a bilirubin of 3.1/0.4 mg/dL. Five months later, his bilirubin was 0.2 mg/dL. His genetic testing came back positive for a heterozygous mutation for Gilbert Syndrome. In the UGT1A1 gene he had the following mutations: heterozygous *28 (TA 6/7) (c. 40-39insTA), heterozygous *60 (c-3275T>G), and heterozygous *93 (c.- 3152G>A). This result is consistent with a carrier state for unconjugated hyperbilirubinemia and may be associated with mild to moderate hyperbilirubinemia. The relevance of this haplotype of polymorphisms to hyperbilirubinemia in the neonate has not been established. Gilbert syndrome is the most common hereditary cause of increased bilirubin but is typically associated with mild hyperbilirubinemia, around 3 mg/dL. In the homozygous state, diminished bilirubin glucuronidation is observed but it is questionable if the same amount of decreased activity can be seen in the heterozygous state. It has been proposed that when additional mutations exist in conjunction with a heterozygous state, neonatal hyperbilirubinemia is more pronounced. We believe that unexplained unconjugated hyperbilirubinemia should raise the suspicion of a UGT1A1 gene mutation and should prompt genetic testing. Gilbert syndrome should be added to the differential of severe unconjugated hyperbilirubinemia in the neonate