Microphthalmia, and Increased serum lactate

High match OCULOCEREBRORENAL SYNDROME OF LOWE

Oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, glaucoma, intellectual disabilities, postnatal growth retardation and renal tubular dysfunction with chronic renal failure.

OCULOCEREBRORENAL SYNDROME OF LOWE Is also known as oculocerebrorenal dystrophy|phosphatidylinositol 4,5-biphosphate 5-phosphatase deficiency|oculo-cerebro-renal dystrophy|oculo-cerebro-renal syndrome|lowe disease|ocrl1|ocrl|ocr|lowe syndrome|phosphatidylinositol 4,5-bisphosphate 5-phosphatase deficiency|l

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Low match OPTIC ATROPHY-PERIPHERAL NEUROPATHY-DEVELOPMENTAL DELAY SYNDROME

Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. Other more variable features such as optic atrophy may also occur. Laboratory studies in some patients show evidence of mitochondrial dysfunction (summary by Harel et al., 2016).

OPTIC ATROPHY-PERIPHERAL NEUROPATHY-DEVELOPMENTAL DELAY SYNDROME Is also known as harel-yoon syndrome

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

SOURCES: ORPHANET OMIM MENDELIAN

Low match DEVELOPMENTAL DELAY DUE TO METHYLMALONATE SEMIALDEHYDE DEHYDROGENASE DEFICIENCY

Developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency is a rare, genetic, inborn error of branched-chain amino acid metabolism disorder, with a highly variable clinical and biochemical phenotype, typically characterized by mild to severe global developmental delay, elevated methylmalonic acid and, occasionally, lactic acid plasma levels, and chronic methylmalonic aciduria, which may be accompanied by elevation of additional organic or amino acids in urine (e.g. beta-alanine, methionine, 3-hydroxypropionic, 3-aminoisobutyric and/or 3-hydroxyisobutyric acid). Microcephaly, mild craniofacial dysmorphism, axial hypotonia, liver failure, and central nervous system abnormalities on MRI have also been reported.

DEVELOPMENTAL DELAY DUE TO METHYLMALONATE SEMIALDEHYDE DEHYDROGENASE DEFICIENCY Is also known as mmsdh deficiency|developmental delay due to aldh6a1 deficiency|developmental delay due to mmsdh deficiency

• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Hypertelorism
• Abnormal facial shape

SOURCES: ORPHANET OMIM MESH MENDELIAN

Low match BARTTER SYNDROME, TYPE 2, ANTENATAL; BARTS2

Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997).Patients with antenatal forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, {607364}) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012).For a discussion of genetic heterogeneity of Bartter syndrome, see {607364}.

BARTTER SYNDROME, TYPE 2, ANTENATAL; BARTS2 Is also known as hypokalemic alkalosis with hypercalciuria 2, antenatal|hyperprostaglandin e syndrome 2

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Failure to thrive

SOURCES: OMIM MENDELIAN

Low match BARTTER SYNDROME, TYPE 4A, NEONATAL, WITH SENSORINEURAL DEAFNESS; BARTS4A

Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997).Patients with antenatal (or neonatal) forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, {607364}) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012).For a discussion of genetic heterogeneity of Bartter syndrome, see {607364}.

BARTTER SYNDROME, TYPE 4A, NEONATAL, WITH SENSORINEURAL DEAFNESS; BARTS4A Is also known as bartter syndrome, neonatal, with sensorineural deafness|bsnd

• Intellectual disability
• Generalized hypotonia
• Hearing impairment
• Failure to thrive
• Sensorineural hearing impairment

SOURCES: OMIM MENDELIAN

Low match MICROPHTHALMIA, ISOLATED 7; MCOP7

• Microphthalmia

SOURCES: OMIM MENDELIAN

Low match MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 7; MCOPCB7

• Microphthalmia
• Coloboma

SOURCES: OMIM MENDELIAN

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

• Global developmental delay
• Acidosis
• Hypoglycemia
• Metabolic acidosis
• Increased serum lactate

SOURCES: OMIM MENDELIAN

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 21

Combined oxidative phosphorylation defect type 21 is a rare mitochondrial disease characterized by axial hypotonia with limb hypertonia, developmental delay, hyperlactatemia, central nervous system anomalies visible on magnetic resonance imaging (e.g. corpus callosum hypoplasia, lesions of the globus pallidus) and multiple deficiency of the mitochondrial respiratory chain complexes in muscle tissue, but not in fibroblasts or liver.

COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 21 Is also known as coxpd21

• Global developmental delay
• Generalized hypotonia
• Hypoplasia of the corpus callosum
• Hypertonia
• Muscular hypotonia of the trunk

SOURCES: ORPHANET OMIM MENDELIAN

Low match COMBINED OXIDATIVE PHOSPHORYLATION DEFECT TYPE 23

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 DEFECT TYPE 23 Is also known as coxpd23

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

SOURCES: ORPHANET OMIM MENDELIAN