A Case with NAD(P)HX Dehydratase (NAXD) Deficiency: A Newly Defined Mutation in a Novel Neurodegenerative Disorder.

Introduction: Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are required redox equivalents for essential biochemical reactions. Their hydrated forms, NADHX and NAD(P)HX, are inhibitors for several dehydrogenases and cause harmful byproducts. NAD(P)HX dehydratase (NAXD) and NAD(P)HX epimerase (NAXE) together form the nicotinamide repair system. Case Presentation: A 7-month-old boy was admitted due to myoclonic seizures, impaired consciousness, and rapid loss of head control. One of his siblings regressed after a febrile seizure and died at 7 months. He had lethargy and axial hypotonia but skin lesions and organomegaly were not noted. Basal metabolic tests were within normal limits except serum and cerebrospinal fluid lactate levels, which were mildly elevated. Mitochondrial cocktail was added to the antiepileptic treatment with suspicion of mitochondrial disease. Whole-exome sequencing showed a novel homozygous mutation (c.247G>A) in the Discussion: Prominent features of NAXD deficiency are progressive neurological deterioration after fever, cardiomyopathy, skin lesions, and premature death. Unlike the cases reported in the literature, our patient had neither preceding fever nor skin lesion during follow-up. It appears that cases show phenotypic diversity.