Cardiomyopathy, and Skeletal dysplasia

Low match PEROXISOME BIOGENESIS DISORDER 9B; PBD9B

While most patients of PBD complementation group 11 manifest rhizomelic chondrodysplasia punctata (RCDP1 ), a few have been reported with unusually mild phenotypes with longer survival, less neurologic involvement, normal or near-normal growth, and absence of rhizomelia (Braverman et al., 2002). In some cases this phenotype was indistinguishable from that of classic Refsum disease (OMIM ) and patients carried this diagnosis.Individuals with PBDs of complementation group 11 (CG11, equivalent to CGR) have mutations in the PEX7 gene. For information on the history of PBD complementation groups, see {214100}.

PEROXISOME BIOGENESIS DISORDER 9B; PBD9B Is also known as refsum disease, adult, 2|peroxisome biogenesis disorder, pex7-related, atypical

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia

SOURCES: OMIM MENDELIAN

Low match HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6; CHNG6

• Intellectual disability
• Short stature
• Growth delay
• Hypertelorism
• Abnormal facial shape

SOURCES: OMIM MENDELIAN

Low match D-2-HYDROXYGLUTARIC ACIDURIA

D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare clinically variable neurological form of 2-hydroxyglutaric aciduria (see this term) characterized biochemically by elevated D-2-hydroxyglutaric acid (D-2-HG) in the urine, plasma and cerebrospinal fluid.

D-2-HYDROXYGLUTARIC ACIDURIA Is also known as d-2-hga|d-2-hydroxyglutaric acidemia|d2hga

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

SOURCES: OMIM ORPHANET MENDELIAN

Low match REFSUM DISEASE, CLASSIC

Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. However, not all patients show all these features. All patients have accumulation of an unusual branched-chain fatty acid, phytanic acid, in blood and tissues. Other variable features include cardiac dysfunction, nerve deafness, ichthyosis, and multiple epiphyseal dysplasia (review by Skjeldal et al., 1987).Increased levels of phytanic acid can also be found in peroxisomal biogenesis disorders; see Zellweger syndrome (see {214100}) (Skjeldal et al., 1987).Infantile Refsum disease (see PBD1B, {601539}) is a distinct disorder with a different phenotype and genetic basis.A phenotype clinically indistinguishable from that of classic Refsum disease (PBD9B ), but with a different biochemical profile, can be caused by mutation in the gene encoding peroxin-7 (PEX7 ) on chromosome 6q.

REFSUM DISEASE, CLASSIC Is also known as heredopathia atactica polyneuritiformis|hmsn iv|phytanic acid oxidase deficiency|hereditary motor and sensory neuropathy iv|hmsn4|refsum disease, adult, 1

• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia
• Nystagmus

SOURCES: OMIM MENDELIAN

Low match REFSUM DISEASE

Refsum disease (RD) is a very rare, clinically variable, multisystemic metabolic disease, characterized by anosmia, early-onset retinitis pigmentosa and possible neurological manifestations, including neuropathy, and cerebellar ataxia, deafness, ichthyosis, skeletal abnormalities, and cardiac arrhythmia. It is characterized biochemically by accumulation of phytanic acid in plasma and tissues.

REFSUM DISEASE Is also known as hmsn 4|phytanic-coa hydroxylase deficiency|heredopathia atactica polyneuritiformis|classic refsum disease|hereditary motor and sensory neuropathy type 4|adult refsum disease

• Ataxia
• Nystagmus
• Sensorineural hearing impairment
• Muscular hypotonia
• Cataract

SOURCES: ORPHANET MENDELIAN

Low match ALG12-CDG

ALG12-CDG is a form of congenital disorders of N-linked glycosylation characterized by facial dysmorphism (prominent forehead, large ears, thin upper lip), generalized hypotonia, feeding difficulties, moderate to severe developmental delay, progressive microcephaly, frequent upper respiratory tract infections due to impaired immunity with decreased immunoglobulin levels, and decreased coagulation factors. Additional features include hypogonadism with or without hypospadias in males, skeletal anomalies, seizures and cardiac anomalies in some cases. ALG12-CDG is caused by loss of function mutations of the gene ALG12 (22q13.33).

ALG12-CDG Is also known as cdg1g|mannosyltransferase 8 deficiency|congenital disorder of glycosylation type ig|cdgig|cdg ig|carbohydrate deficient glycoprotein syndrome type ig|cdg syndrome type ig|congenital disorder of glycosylation type 1g|cdg-ig

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: MESH OMIM ORPHANET MENDELIAN

Low match SCHINDLER DISEASE, TYPE I

Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy; type II, also known as Kanzaki disease (OMIM ), is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder with mild to moderate neurologic manifestations (Desnick and Schindler, 2001).

SCHINDLER DISEASE, TYPE I Is also known as neuroaxonal dystrophy, schindler type|naga deficiency, type i|alpha-n-acetylgalactosaminidase deficiency, type i

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

SOURCES: OMIM ORPHANET MENDELIAN

Low match NEURAMINIDASE DEFICIENCY

Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (OMIM ) is a form of 'free' sialic acid disease. ClassificationLowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.

NEURAMINIDASE DEFICIENCY Is also known as neug deficiency|neuraminidase 1 deficiency|glycoprotein neuraminidase deficiency|neu1 deficiency|mucolipidosis i|neu deficiency|lipomucopolysaccharidosis|sialidase deficiency|ml i|sialidosis, type ii

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

SOURCES: OMIM MENDELIAN

Low match MUCOPOLYSACCHARIDOSIS-LIKE SYNDROME WITH CONGENITAL HEART DEFECTS AND HEMATOPOIETIC DISORDERS

MPSPS is an autosomal recessive inborn error of metabolism resulting in a multisystem disorder with features of the mucopolysaccharidosis lysosomal storage diseases (see, e.g., {607016}). Patients present in infancy or early childhood with respiratory difficulties, cardiac problems, anemia, dysostosis multiplex, renal involvement, coarse facies, and delayed psychomotor development. Most patients die of cardiorespiratory failure in the first years of life (summary by Kondo et al., 2017).

MUCOPOLYSACCHARIDOSIS-LIKE SYNDROME WITH CONGENITAL HEART DEFECTS AND HEMATOPOIETIC DISORDERS Is also known as mucopolysaccharidosis-like plus disease

• Global developmental delay
• Abnormal facial shape
• Spasticity
• Anemia
• Flexion contracture

SOURCES: OMIM ORPHANET MENDELIAN

Low match BETA-THALASSEMIA MAJOR

Beta-thalassemia (BT) major is a severe early-onset form of BT (see this term) characterized by severe anemia requiring regular red blood cell transfusions.

BETA-THALASSEMIA MAJOR Is also known as cooley anemia|mediterranean anemia

• Hearing impairment
• Muscle weakness
• Cataract
• Anemia
• Feeding difficulties

SOURCES: ORPHANET MENDELIAN