# Deficiency of the NAD(P)HX metabolic repair system: a treatable mitochondrial disease

## TL;DR

This study shows that nicotinamide treatment improves survival and quality of life in patients with a rare mitochondrial disease caused by NAD(P)HX metabolic deficiency.

## Contribution

The study demonstrates that early nicotinamide treatment significantly improves prognosis in NAD(P)HX metabolic deficiency, a previously poorly understood mitochondrial disease.

## Key findings

- Patients treated with nicotinamide had an 80.95% survival rate compared to 85.45% mortality in untreated patients.
- Three treated patients were able to attend school normally with no significant adverse effects from treatment.

## Abstract

This study aims to explore the clinical characteristics of patients with NAD(P)HX metabolic deficiency and their prognosis after nicotinamide treatment.

This study retrospectively analyzed the clinical characteristics, efficacy of nicotinamide treatment, and prognosis of patients with genetically confirmed NAD(P)HX metabolic defects admitted to Beijing Children’s Hospital from January 2016 to January 2025, as well as cases previously reported in the literature. The log-rank test was used for survival analysis, and the prognosis was evaluated using the Modified Rankin Scale (mRS).

Nine patients were analyzed, including eight with NAXE deficiency and one with NAXD deficiency, seven of whom received nicotinamide treatment (180–500 mg/day). With a median follow-up of 3.92 years [range: 0.50–6 years, interquartile range (IQR) = 2.42 years], the overall prognosis was favourable. All seven treated patients survived, three of whom were able to attend school normally, and no significant adverse reactions were observed during treatment. Combined with previous studies, a total of 59 patients were included for analysis (14 cases of NAXD deficiency and 45 cases of NAXE deficiency), with an overall mortality rate of 66.7%. Among the 21 patients who received niacin/nicotinamide treatment, 17 survived (80.95%), whereas only two untreated patients survived, and 85.45% of the untreated patients died within 2 years of onset. Respiratory failure was the most common cause of death.

NAD(P)HX metabolic defects are rare mitochondrial diseases with high mortality and morbidity rates. Early identification and timely initiation of nicotinamide treatment are crucial for improving patient prognosis and quality of life.

The online version contains supplementary material available at 10.1186/s13023-026-04218-4.