# Treatable Neonatal Molybdenum Cofactor Deficiency: Rapid Demise Despite Rapid Biochemical Diagnosis

## TL;DR

A rare metabolic disorder called MoCD was diagnosed quickly in a newborn, but the patient died before treatment could be given, highlighting the need for faster diagnostics and better treatment access.

## Contribution

This case highlights the importance of rapid biochemical diagnosis and treatment access for MoCD, a rare metabolic disorder.

## Key findings

- A patient with MoCD Type A was diagnosed within 24 hours through biochemical testing but died before treatment could be administered.
- Genome sequencing confirmed double homozygous pathogenic variants in MOCS1.
- The patient's condition deteriorated faster than previously reported in the literature.

## Abstract

Molybdenum cofactor deficiency (MoCD) is an inborn error of metabolism included in the differential for refractory neonatal seizures. The prognosis is guarded, with a median reported age of death between 2.4 and 3.0 years. Mortality is primarily due to seizures and lower respiratory tract infections. MoCD has a distinct biochemical profile, characterized by elevated urinary S‐sulfocysteine, xanthine, and hypoxanthine, and low or undetectable serum and urine uric acid levels. A disease‐altering treatment is available for MoCD Type A; however, due to the rarity of the condition, its natural history remains poorly understood. We present a patient with neonatal‐onset refractory seizures, whose biochemical testing, performed within 24 h of specimen receipt in the laboratory, revealed a pattern consistent with MoCD. Before the genetics team could disclose the preliminary diagnosis, the patient demised, without evidence of worsening seizures or respiratory infection. Results of genome sequencing, guided by biochemical findings, identified double homozygous pathogenic variants in MOCS1 (associated with MoCD Type A). Although the biochemical genetics laboratory's protocol for analyzing and reporting S‐sulfocysteine levels within 48 h enabled a rapid preliminary diagnosis, the patient's condition deteriorated too quickly to initiate disease‐altering treatment, progressing more rapidly than described in the literature. We discuss potential hypotheses for his rapid decline and the broader implications for the field of biochemical genetics.

As more disease‐altering treatments emerge for inborn errors of metabolism, this case underscores the urgent need for robust natural history data, faster diagnostics, and more readily available treatments, especially at large academic medical centers.