Background ALAD-Porphyria (ADP) is an ultrarare porphyria, with only eight documented cases previously reported in literature. Infantile onset of symptoms was reported in only 2 cases. Herein, we report another such case, and the second known case of ADP in the Western hemisphere.

Case Presentation A male Hispanic neonate presented on day three of life with profound hypotonia, pinpoint pupils, absent deep tendon reflexes, and anemia. Whole genome sequencing revealed two pathogenic missense ALAD variants each inherited from one parent: c.397G>A (p.Gly133Arg) and c.415G>A (p.Gly139Arg). Biochemical testing on day 21 of life (15 days after erythrocyte transfusion) showed substantial elevation in urinary ALA (30 mg/g creatinine, ref <7) and total porphyrins (5,038 nmol/g creatinine, ref <300; 96% coproporphyrin III) and erythrocyte protoporphyrin (total 286 ug/dL (ref <80, 85% zinc protoporphyrin, 15% metal-free protoporphyrin), as expected in ADP. Erythrocyte ALAD enzyme activity was mildly decreased; however, this was measured after packed red blood cell transfusion. With supportive care in the neonatal intensive care unit his hypotonia improved gradually until he was safely discharged home on day 34 of life. He has continued to improve during outpatient follow up, and additional transfusions were not required.

Discussion Ultrarare autosomal recessive forms of porphyria, such as ADP, should be suspected as a cause of neonatal-onset hypotonia. Diagnosis is made by biochemical testing, but is facilitated by broad genetic testing methods. Both the marrow and liver may contribute to overproduction of ALA and porphyrins in ADP. Improvement in this patient may have resulted from erythrocyte transfusion and decreased erythropoiesis and less overproduction of ALA and porphyrins by the marrow, and this may be an important consideration for long term management.