Delayed speech and language development, and Lactic acidosis

Medium match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 17; COXPD17

Combined oxidative phosphorylation deficiency-17 is an autosomal recessive disorder of mitochondrial dysfunction characterized by onset of severe hypertrophic cardiomyopathy in the first year of life. Other features include hypotonia, poor growth, lactic acidosis, and failure to thrive. The disorder may be fatal in early childhood (summary by Haack et al., 2013).

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 17; COXPD17 Is also known as ;coxpd17

• Autosomal recessive inheritance
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: UMLS OMIM ORPHANET MONDO

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 23; COXPD23

Combined oxidative phosphorylation deficiency-23 is an autosomal recessive disorder characterized by early childhood onset of hypertrophic cardiomyopathy and/or neurologic symptoms, including hypotonia and delayed psychomotor development. Laboratory investigations are consistent with a defect in mitochondrial function resulting in lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Brain imaging shows abnormal lesions in the basal ganglia, thalamus, and brainstem. The severity of the disorder is variable, ranging from death in early infancy to survival into the second decade (summary by Kopajtich et al., 2014).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 23; COXPD23 Is also known as ;coxpd23

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: EFO UMLS OMIM MONDO ORPHANET

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 18; COXPD18

Combined oxidative phosphorylation deficiency-18 is an autosomal recessive disorder of mitochondrial function characterized by intrauterine growth retardation, hypotonia, visual impairment, speech delay, and lactic acidosis associated with decreased mitochondrial respiratory chain activity. Affected patients may also show hematologic abnormalities, mainly macrocytic anemia (summary by Hildick-Smith et al., 2013).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 18; COXPD18 Is also known as ;

• Autosomal recessive inheritance
• Intellectual disability
• Generalized hypotonia
• Growth delay
• Anemia

SOURCES: ORPHANET MONDO OMIM UMLS

Low match MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 WITH HYPERGLYCINEMIA; MMDS2

Multiple mitochondrial dysfunctions syndrome-2 (MMDS2) with hyperglycinemia is a severe autosomal recessive disorder characterized by developmental regression in infancy. Affected children have an encephalopathic disease course with seizures, spasticity, loss of head control, and abnormal movement. Additional more variable features include optic atrophy, cardiomyopathy, and leukodystrophy. Laboratory studies show increased serum glycine and lactate. Most patients die in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; {605899}), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including MMDS2, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014).For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (OMIM ).

MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 2 WITH HYPERGLYCINEMIA; MMDS2 Is also known as ;bola3 deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: ORPHANET OMIM UMLS MONDO DOID

Low match NEURODEVELOPMENTAL DISORDER, MITOCHONDRIAL, WITH ABNORMAL MOVEMENTS AND LACTIC ACIDOSIS, WITH OR WITHOUT SEIZURES; NEMMLAS

NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding (summary by Wortmann et al., 2017).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia

SOURCES: OMIM

Low match MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 3; MC3DN3

• Autosomal recessive inheritance
• Global developmental delay
• Motor delay
• Acidosis
• Hypoglycemia

SOURCES: OMIM DOID UMLS MONDO

Low match CHROMOSOME 15q11-q13 DUPLICATION SYNDROME

The features of the chromosome 15q11-q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delays, and behavioral problems (Bundey et al., 1994; Burnside et al., 2011).See also chromosome 15q13.3 deletion syndrome (OMIM ) and chromosome 15q11.2 deletion syndrome (OMIM ).For a discussion of genetic heterogeneity of autism, see {209850}.

CHROMOSOME 15q11-q13 DUPLICATION SYNDROME Is also known as duplication 15q11-q13 syndrome;15q11-q13 duplication syndrome; 15q11-q13 microduplication syndrome; 15q11q13 duplication syndrome; dup(15)(q11q13); trisomy 15q11-q13; trisomy 15q11q13

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: NCIT SCTID MONDO OMIM ORPHANET UMLS

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 12; COXPD12

COXPD12 is an autosomal recessive mitochondrial neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability (summary by Steenweg et al., 2012).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 12; COXPD12 Is also known as leukoencephalopathy with thalamus and brainstem involvement and high lactate;ltbl;coxpd12; combined oxidative phosphorylation defect type 12; ltbl

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive

SOURCES: MONDO UMLS GARD ORPHANET OMIM

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 14; COXPD14

COXPD14 is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes. Neuropathologic studies in 1 patient showed laminar cortical necrosis, characteristic of Alpers syndrome (OMIM ) (summary by Elo et al., 2012).For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (OMIM ).

COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 14; COXPD14 Is also known as ;coxpd14

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: MONDO OMIM ORPHANET UMLS

Low match HSD10 MITOCHONDRIAL DISEASE; HSD10MD

HSD10 mitochondrial disease most commonly presents as an X-linked neurodegenerative disorder with highly variable severity and age at onset ranging from the neonatal period to early childhood. The features are usually multisystemic, consistent with mitochondrial dysfunction. Some affected males have a severe infantile form associated with cardiomyopathy that may result in death in early childhood, whereas other rare patients may have juvenile onset or even atypical presentations with normal neurologic development. More severely affected males show developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation. Heterozygous females may show non-progressive developmental delay and intellectual disability, but may also be clinically normal. Although the diagnosis can be aided by the observation of increased urinary levels of metabolites of isoleucine breakdown (2-methyl-3 hydroxybutyrate and tiglylglycine), there is not a correlation between these laboratory features and the phenotype. In addition, patients do not develop severe metabolic crises in the neonatal period as observed in other organic acidurias, but may show persistent lactic acidosis, most likely reflecting mitochondrial dysfunction (summary by Rauschenberger et al., 2010; review by Zschocke, 2012).In a review of the disorder, Zschocke (2012) noted that although this disorder was originally thought to be an inborn error of branched-chain fatty acid and isoleucine metabolism resulting from decreased HSD17B10 dehydrogenase activity (HSD17B10 'deficiency'), subsequent studies have shown that the HSD17B10 gene product has additional functions and also acts as a component of the mitochondrial RNase P holoenzyme, which is involved in mitochondrial tRNA processing and maturation and ultimately mitochondrial protein synthesis. The multisystemic features of HSD10MD most likely result from the adverse effect of HSD17B10 mutations on mitochondrial function, rather than from the effects on the dehydrogenase activity (see PATHOGENESIS below).

HSD10 MITOCHONDRIAL DISEASE; HSD10MD Is also known as hsd17b10 deficiency, 17-beta-hydroxysteroid dehydrogenase x deficiency, 3-hydroxyacyl-coa dehydrogenase ii deficiency, 2-methyl-3-hydroxybutyryl-coa dehydrogenase deficiency, mhbd deficiency, mental retardation, x-linked, syndromic 10;mrxs10, chorioathetosis with mental retardation and abnormal behavior;camr, mental retardation with chorioathetosis and abnormal behavior

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: SCTID ORPHANET UMLS OMIM