The Expanded Newborn Screening implemented in the Community of Madrid, Spain allowed for the identification of 222 cases (incidence, 1/2670) of inborn errors of metabolism (IEM) over a period of 9 years, as published in JIMD Reports. Overall, the authors found that only 8.5% of the infants included in the study were symptomatic at the time of the screening result.

“In our program, genetic diagnosis not only has confirmed all the biochemical cases (except for two) but also has allowed to detect novel IEM, as [hyperphenylalaninemia] due to DNAJC12 pathogenic variants and [branched‐chain amino acid transferase 2] deficiency,” they said.

Among the disorders identified are long chain fatty acid oxidation disorders (LCFAODs), such as carnitine palmitoyltransferase (CPT 1, n=1, or CPT 2, n=2) deficiency, very long-chain acyl-CoA dehydrogenase (VLCAD, n=13) deficiency, and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD, n=2) deficiency.

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None of the newborns diagnosed with VLCAD deficiency and CPT 1 deficiency had clinical symptoms before the diagnosis. On the other hand, half of the patients with CPT 2 deficiency or LCHAD deficiency presented with clinical symptoms at diagnosis.

“One of the patients diagnosed with [LCHAD deficiency] had a very early and fatal onset. This disease usually displays immediate complications, but recent data have shown that outcomes can be favorable if early diagnosis and strict dietary regime are initiated,” the authors said.

The patient experienced acute respiratory distress and poor perfusion of peripheral tissues (dilated cardiomyopathy) and died at the age of 6 months. Symptoms started on the first day of life. Biochemical analyses revealed hypoglycemia, metabolic acidosis, elevated lactate, hyperammonemia, and creatine phosphokinase (CPK) elevation. Detoxification measures included glucose and bicarbonate infusion.

Newborn Testing Reveals Higher Incidence of Fatty Acid Disorders

One of the patients with CPT 2 deficiency experienced symptoms since the seventh day of life. Clinical manifestations at diagnosis included acute encephalopathy and seizures. Biochemical analyses showed hypoglycemia and hyperammonemia. The patient was managed with glucose infusion.


Martín‐Rivada Á, Palomino Pérez L, Ruiz‐Sala P, et al. Diagnosis of inborn errors of metabolism within the expanded newborn screening in the Madrid region. JIMD Rep. Published online January 27, 2022. doi:10.1002/jmd2.12265