Newborn screening for severe combined immunodeficiency: an opportunity for intervention.

Severe combined immunodeficiency (SCID) is a potentially fatal disorder characterized by defective T- and B-lymphocyte function. We describe a 34-week female twin who had developed feeding intolerance, perioral cyanosis, abdominal distension and neutropenia at 1 month of age. Despite several evaluations including an 'inconclusive' newborn screening result for SCID, the presence of profound lymphopenia was unappreciated. Eventually a diagnosis of SCID in association with adenosine deaminase deficiency was made. This case serves to emphasize the importance of newborn screening for SCID in the context of careful evaluation of clinical and laboratory findings that may be overlooked and result in a delay in the diagnosis of a potentially life-threatening condition.

Pearson syndrome: unique endocrine manifestations including neonatal diabetes and adrenal insufficiency.

PURPOSE: Pearson syndrome is a very rare metabolic disorder that is usually present in infancy with transfusion dependent macrocytic anemia and multiorgan involvement including exocrine pancreas, liver and renal tubular defects. The disease is secondary to a mitochondrial DNA deletion that is variable in size and location. Endocrine abnormalities can develop, but are usually not part of the initial presentation. We report two patients who presented with unusual endocrine manifestations, neonatal diabetes and adrenal insufficiency, who were both later diagnosed with Pearson syndrome. METHODS: Medical records were reviewed. Confirmatory testing included: mitochondrial DNA deletion testing and sequencing of the breakpoints, muscle biopsy, and bone marrow studies. RESULTS: Case 1 presented with hyperglycemia requiring insulin at birth. She had several episodes of ketoacidosis triggered by stress and labile blood glucose control. Workup for genetic causes of neonatal diabetes was negative. She had transfusion dependent anemia and died at 24 months due to multisystem organ failure. Case 2 presented with adrenal insufficiency and anemia during inturcurrent illness, requiring steroid replacement since 37 months of age. He is currently 4 years old and has mild anemia. Mitochondrial DNA studies confirmed a 4.9 kb deletion in patient 1 and a 5.1 kb deletion in patient 2. CONCLUSION: The patients reported highlight the importance of considering mitochondrial DNA disorders in patients with early onset endocrine dysfunction, and expand the knowledge about this rare mitochondrial disease.