Transient neonatal renal failure and massive polyuria in MEGDEL syndrome

Abstract

BackgroundMEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome) syndrome is a mitochondrial disorder associated with recessive mutations in SERAC1.ObjectivesTo report transient neonatal renal findings in MEGDEL syndrome.ResultsThis 7 year-old girl was the first child of consanguineous Turkish parents. She exhibited an acute neonatal deterioration with severe lactic acidosis and liver failure. Initial evaluation revealed massive polyuria and renal failure with 3-methylglutaconic aciduria. Symptoms and biological findings progressively improved with symptomatic treatment but lactic acidosis and high lactate to pyruvate ratio along with 3-methylglutaconic aciduria persisted. At 8 months of age, a subacute neurological degradation occurred with severe hypotonia, dystonia with extrapyramidal movements and failure to thrive. Brain MRI revealed basal ganglia lesions suggestive of Leigh syndrome. At 3 years of age, sensorineural deafness was documented. MEGDEL syndrome was further confirmed by the identification of an already reported homozygous mutation in SERAC1.ConclusionTransient neonatal polyuria and renal failure have not been reported to date in SERAC1 defective patients. Such neonatal kidney findings expand the clinical spectrum of MEGDEL syndrome.

Cerebral imaging in paediatric mitochondrial disorders

“…66 Hyperintensities of the putamen and the cortex have been reported in patients with primary coenzyme-Q-deficiency. 67 T2-hyperintensities of the thalamus, inferior olives, and the cerebellum were found in patients with sensory ataxic neuropathy, dysarthria and ophthalmoplegia. 68 In a study of 15 patients with childhood- to adulthood-onset mitochondrial membrane protein-associated neurodegeneration due to C19orf12 gene mutations, MRI revealed bilateral T2-hyperintensities of the globus pallidus and substantia nigra without an eye-of-the-tiger sign but with frequent streaking of the medial medullary lamina between the external and internal parts of the globus pallidus.…”

Progressive deafness–dystonia due to SERAC1 mutations: A study of 67 cases

“…A total of 67 individuals from 59 families were included, of whom 28 individuals have been published previously (P1–15, P35, P42, P49, P50, P51–52, P58, P60–64, and P66 …”

“…Variants were found either by Sanger sequencing, exome sequencing as previously described,2, 9, 10, 11, 12, 13, 14, 15 or genome sequencing 16. All variants found in individuals, and carrier status of parents, were confirmed by Sanger sequencing (details available upon request).…”

“…Urinary organic acid analysis; serum/plasma amino acid analysis; histological and immunohistochemical evaluation, measurement of the oxidative phosphorylation system (OXPHOS), and quantitation of mtDNA in muscle, liver, or cultured fibroblasts; and filipin staining in cultured fibroblasts were performed using standard methods as described before. 2,8 Identification of SERAC1 Variants Variants were found either by Sanger sequencing, exome sequencing as previously described, 2,[9][10][11][12][13][14][15] or genome sequencing. 16 All variants found in individuals, and carrier status of parents, were confirmed by Sanger sequencing (details available upon request).…”

Phenotypic Variability of Leigh Syndrome Due to the ATP6/ATP8 Variant M.8561T>C

“…Serum lactate was slightly elevated but lactate levels in the cerebrospinal fluid (CSF), or MR-spectroscopy were not provided. Cerebral lactate is frequently elevated on LS [2].…”