This article highlights the phenotypic manifestations from a novel mutation in the C12orf65 gene and reviews the clinical presentation of the 5 other individuals reported to date who carry mutations in this gene. [collections.lib.utah.edu]

The first is the severe form, usually presented within the period of infancy and characterized by acute metabolic decompensation with a rapid deterioration, often presenting with CHF, severe hyperlactacidemia, and consequently early death. [frontiersin.org]

The first subgroup, with neonatal presentation, is characterized by cardiomyopathy and is frequently fatal in early life. The second subgroup presents in infancy, with hypoketosis and hypoglycaemia, and frequently mimics Reye-Syndrome [ 111, 112 ]. [bioscirep.org]

Seizures may be present at birth or within the first month of life. Edema of the feet, hands, and face are also present at birth. Cognitive deficits and motor delays are usually evident during infancy. [disorders.eyes.arizona.edu]

Alpers syndrome is a progressive neurodegenerative disorder that presents in infancy or early childhood and is characterized by diffuse degeneration of cerebral gray matter. {ECO:0000269 PubMed:25385316, ECO:0000269 PubMed:25629079}. [genecards.org]

• Developmental Delay

  We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of [collections.lib.utah.edu]

  Patients 2 and 3 presented with a mild form, with developmental delay, fatigability, and hyperlactacidemia. [frontiersin.org]

  Infants within the first 4 to 6 months of life had evidence of developmental delay and neurodevelopmental regression. Poor feeding and breathing difficulties are often noted in this period. [disorders.eyes.arizona.edu]

  Global developmental delay MedGen UID: 107838 •Concept ID: C0557874 • Finding A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social [ncbi.nlm.nih.gov]

  In addition, cardiomyopathy, developmental delay and metabolic acidosis are common, with death mostly under the age of 1 year [ 120 – 124 ] ( Table 3 ). [bioscirep.org]

• Epilepsy

  myoclonic, progressive, type 4, with or without renal failure (EPM-4) 254900 0 0 SCARB2 - - 04347 FAME-2;FMCTE-2 epilepsy, myoclonic, familial adult, type 2 (FAME-2) 607876 0 0 ADRA2B, STARD7 - - 05587 FAME-3;FMCTE-3 epilepsy, myoclonic, familial adult [databases.lovd.nl]

  juvenile myoclonic, susceptibility to, 8} 607628 600570 Autosomal dominant CLCN2 3q27.1 {Epilepsy, juvenile absence, susceptibility to, 2} 607628 600570 Autosomal dominant CLCN2 3q27.1 {Epilepsy, idiopathic generalized, susceptibility to, 11} 607628 [mnglabs.com]

  IRE 21q22.3 Autoimmune polyendocrinopathy syndrome, type I, with or without reversible metaphyseal dysplasia 240300 A LDH3A2 17p11.2 Sjogren-Larsson syndrome 270200 A LDH5A1 6p22.3 Succinic semialdehyde dehydrogenase deficiency 271980 A LDH7A1 5q23.2 Epilepsy [institutobernabeu.com]

  […] controlled vocabulary of human diseases New diseases: Amelogenesis imperfecta 1A Amelogenesis imperfecta 1H Charcot-Marie-Tooth disease 2T CODAS syndrome Combined oxidative phosphorylation deficiency 23 Combined oxidative phosphorylation deficiency 24 Epilepsy [uniprot.org]

  {Epilepsy, childhood absence, susceptibility to, 5}, 612269 (3) GABRD G:137163. {Epilepsy, idiopathic generalized, 10}, 613060 (3) GABRD G:137163. {Epilepsy, juvenile myoclonic, susceptibility to}, 613060 (3) GABRD G:137163. [usegalaxy.org]

• Disability

  […] pulmonary hypertension, renal failure, and alkalosis (HUPRAS) 613845 0 0 SARS2 - autosomal recessive 02131 HYPT-8 hypotrichosis, type 8 (HYPT-8) 278150 0 0 LPAR6 - - 02173 HYSP-1 hypospadias, type 1, X-linked (HYSP-1) 300633 1 1 AR - - 00139 ID intellectual disability [databases.lovd.nl]

  Elmas et al. (2019) also described a 10-year- old girl with GTPBP3 mutations, characterized by early childhood onset of mental motor retardation, seizure, hearing disability, and delayed myelination. [frontiersin.org]

  KDM6A Xp11.3 Kabuki syndrome 2 300867 300128 X-linked dominant KHK 2p23.3 [Fructosuria] 229800 614058 Autosomal recessive KIAA0319 6p22.3 {Dyslexia, susceptibility to, 2} 600202 609269 Autosomal dominant KIDINS220 2p25.1 Spastic paraplegia, intellectual disability [mnglabs.com]

  Epilepsy, X-linked, with variable learning disabilities and behavior disorders, 300491 (3) SYN2 G:600755. {Schizophrenia, susceptibility to}, 181500 (3) SYN3 G:602705. . SYNC G:611750. . SYNDIG1 G:614311. . SYNDIG1L G:609999. . [usegalaxy.org]

• Developmental Disorder

  Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families. Nat Genet. 2015 Nov;47(11):1363-9. [disorders.eyes.arizona.edu]

• Congestive Heart Failure

  Unfortunately, the infant’s condition deteriorated progressively, and he died of congestive heart failure (CHF) on the 4th day of life. Patient 2, a girl was born to non-consanguineous healthy parents after an uneventful pregnancy. [frontiersin.org]

  {Congestive heart failure and beta-blocker response, modifier of} (3) ADRB1 GP:109630. [Resting heart rate], 607276 (3) ADRB1 GP:109630. {Congestive heart failure and beta-blocker response, modifier of} (3) ADRB2 GP:109690. [usegalaxy.org]

• Vomiting

  Clinical presentations include hypotonia, Reye-like Syndrome, seizures, apnoea, hepatomegaly, fever, vomiting, diarrhoea and coma [ 109 ]. [bioscirep.org]

• Myopathy

  Most Studied CPEO, Complex I Deficiency, COXPD1, Leigh, LHON, MELAS, MERRF, Myopathy, SANDO [mseqdr.org]

  A case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with progressive cytochrome c oxidase deficiency. Rinsho Shinkeigaku 1989;29:901-8. [acta.tums.ac.ir]

  2 Alpha-B Crystallin-related Fatal Infantile Hypertrophy Myofibrillar Myopathy CSF2RA Colony Stimulating Factor 2 Receptor, Alpha, Low-Affinity Idiopathic Pulmonary Fibrosis (IPF) Pulmonary Surfactant Metabolism Dysfunction 4 CSF2RA-Related Pulmonary [bcm.edu]

  ± CNS PEO Spinal cord Benign infantile mitochondrial myopathy with reversible cytochrome c oxidase (COX) deficiency Isolated Complex I deficit: mtDNA mutations MELAS : tRNA Leu (A3243G & T3271C) Myopathy : tRNA Leu (T3250C, A3251G & A3303G) Riboflavin [neuromuscular.wustl.edu]

  actin, congenital, with cores 161800 102610 Autosomal dominant; Autosomal recessive ACTA1 1q42.13 Myopathy, actin, congenital, with excess of thin myofilaments 161800 102610 Autosomal dominant; Autosomal recessive ACTA1 1q42.13 Nemaline myopathy 3, [mnglabs.com]

• Hearing Impairment

  Type I Stickler syndrome has multiple systemic features such as cleft palate, hearing impairment, premature arthritis, micrognathia, kyphoscoliosis, and some signs such as arachnodactyly that are found in the Marfan syndrome. [disorders.eyes.arizona.edu]

  Sensorineural hearing loss disorder MedGen UID: 9164 •Concept ID: C0018784 • Disease or Syndrome A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. [ncbi.nlm.nih.gov]

  Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 616192 601184 Autosomal recessive DNAJC5 20q13.33 Ceroid lipofuscinosis, neuronal, 4, Parry type 162350 611203 Autosomal dominant DNAJC6 1p31.3 Parkinson disease 19b, [mnglabs.com]

  Microtia, hearing impairment, and cleft palate, 612290 (3) HOXA3 G:142954. . HOXA4 G:142953. . HOXA5 G:142952. . HOXA6 G:142951. . HOXA7 G:142950. . HOXA9 G:142956. . HOXB-AS5 G:610787. . HOXB1 G:142968. . HOXB13 G:604607. . HOXB2 G:142967. . [usegalaxy.org]

• Psychomotor Retardation

  Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. [genecards.org]

  Systemic Features: Newborns are hypotonic and severe psychomotor retardation is evident a few months later. Truncal ataxia and progressive lower limb spasticity are seen later. [disorders.eyes.arizona.edu]

  Psychomotor retardation, epilepsy, and craniofacial dysmorphism, 614501 (3) SNN G:603032. . SNORA11 G:300662. . SNORA12 G:611330. . SNORA45 G:611333. . SNORA5C G:611335. . SNORA62 G:180646. . SNORA63 G:180647. . SNORA73A G:180645. . [usegalaxy.org]

“Diagnostic Workup of Patients with Mitochondrial Diseases,” in Inherited Metabolic Diseases, eds G. F. Hoffmann, J. Zschocke, and W. L. Nyhan (Berlin: Springer), 521–535. [frontiersin.org]

Treatment Treatment Options: No treatment has been reported. [disorders.eyes.arizona.edu]

CLOSE Medical Disclaimer The medical information on this site is provided as an information resource only, and is not to be used or relied on for any diagnostic or treatment purposes. [diseaseinfosearch.org]

Identification and discontinuation of any offending agents and treatment of known pathology should occur promptly. [emedicine.medscape.com]

Whichever the case, treatment of patients with combined OXPHOS CII/FAO defects has proved problematic, as supplementation with essential fatty acids results in metabolic crises [ 129 ]. [bioscirep.org]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. [uniprot.org]

[…] deletion Ataxia, Hypogonadism & Choroidal dystrophy: Multiple deletion Isolated Complex I deficit: Nuclear mutations Clinical features: General Nuclear mutations more common than mitochondrial Onset: Childhood; Mean = 4 to 5 months Male:Female = 3.5:1 Prognosis [neuromuscular.wustl.edu]

PMID: 18206410Free PMC Article Prognosis Koller A, Fazzini F, Lamina C, Rantner B, Kollerits B, Stadler M, Klein-Weigel P, Fraedrich G, Kronenberg F J Intern Med 2020 May;287(5):569-579. Epub 2020 Feb 9 doi: 10.1111/joim.13027. [ncbi.nlm.nih.gov]

VLCAD deficiency can be classified into three main subgroups based on age of onset, each of which correlates closely with clinical severity and prognosis. [bioscirep.org]

However, in many cases of type B lactic acidosis, occult tissue hypoperfusion is now recognized to accompany the primary etiology. Type B is divided into 3 subtypes based on underlying etiology. [emedicine.medscape.com]

Persistent head lag Poor eye contact Progressive neurologic deterioration Spasticity Abnormality of the respiratory system Respiratory failure Respiratory insufficiency Ear malformation Sensorineural hearing loss disorder Growth abnormality Failure to thrive Etiology [ncbi.nlm.nih.gov]

And the newborn’s phenotype (hyperlactacidemia and metabolic acidosis complicated with respiratory acidosis) is highly specific for a disease with a single genetic etiology (Table 1, PP4). [frontiersin.org]

Relevant External Links for NARS2 Genetic Association Database (GAD) NARS2 Human Genome Epidemiology (HuGE) Navigator NARS2 Atlas of Genetics and Cytogenetics in Oncology and Haematology: NARS2 No data available for Genatlas for NARS2 Gene Mutations of [genecards.org]

The pathophysiology and genetics of congenital lipoid adrenal hyperplasia. N Engl J Med 335: 1870, 2005. Article Google Scholar Andersson HC, Frentz J, Martinez JE, Tuck-Muller CM, Bellizaire J. Adrenal insufficiency in Smith-Lemli-Opitz syndrome. [link.springer.com]

Pathophysiologic classification of lactic acidosis. Go to Acute Lactic Acidosis for complete information on this topic. Hyperlactatemia versus lactic acidosis The normal blood lactate concentration in unstressed patients is 0.5-1 mmol/L. [emedicine.medscape.com]

The 5-taurinomethyluridine (τm5U) modification, identified in mt-tRNALeu(UUR) and mt-tRNATrp, is required for accurate decoding of purine-ending codons and prevent misreading of pyrimidine-ending codons, thereby promoting efficient decoding of cognate [frontiersin.org]