Delayed speech and language development, and Dehydration

Medium match ISOBUTYRYL-CoA DEHYDROGENASE DEFICIENCY

gene (11q25).

ISOBUTYRYL-CoA DEHYDROGENASE DEFICIENCY Is also known as ibd deficiency, acyl-coa dehydrogenase family, member 8, deficiency of, acad8 deficiency;isobutyric aciduria

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

SOURCES: GARD MONDO ORPHANET OMIM SCTID MESH UMLS NCIT

Medium 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

Medium match WOODHOUSE-SAKATI SYNDROME

Woodhouse-Sakati syndrome is a multisystemic disorder characterized by hypogonadism, alopecia, diabetes mellitus, intellectual deficit and extrapyramidal signs with choreoathetoid movements and dystonia.

WOODHOUSE-SAKATI SYNDROME Is also known as hypogonadism, alopecia, diabetes mellitus, mental retardation, deafness, and extrapyramidal syndrome, extrapyramidal disorder, progressive, with primary hypogonadism, mental retardation, and alopecia;diabetes-hypogonadism-deafness-intellectual disability syndrome

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Hearing impairment
• Scoliosis

SOURCES: GARD SCTID ORPHANET OMIM MONDO UMLS MESH

Medium match COLD-INDUCED SWEATING SYNDROME 1; CISS1

Cold-induced sweating syndrome is an autosomal recessive disorder characterized in the neonatal period by orofacial weakness with impaired sucking and swallowing resulting in poor feeding necessitating medical intervention. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. During the first year, most infants have spiking fevers. These features, referred to as 'Crisponi syndrome' in infancy, can result in early death without advanced care. After the first 2 years, the abnormal muscle contractions and fevers abate, and most patients show normal psychomotor development. From childhood onward, the most disabling symptoms stem from impaired thermoregulation and disabling abnormal sweating, which can be treated with clonidine. Patients have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Other features include characteristic facial anomalies, such as round face, chubby cheeks, micrognathia, high-arched palate, low-set ears, and depressed nasal bridge, dental decay, camptodactyly, and progressive kyphoscoliosis (summary by Hahn et al., 2010). Genetic Heterogeneity of Cold-Induced Sweating SyndromeCold-induced sweating syndrome-2 (CISS2 ), which is clinically indistinguishable from CISS1, is caused by mutation in the CLCF1 gene (OMIM ) on chromosome 11q13. CISS3 (OMIM ) is caused by mutation in the KLHL7 gene (OMIM ) on chromosome 7p15.

COLD-INDUCED SWEATING SYNDROME 1; CISS1 Is also known as crisponi syndrome, sohar-crisponi syndrome, muscle contractions, tetanoform, with characteristic face, camptodactyly, hyperthermia, and sudden death;ciss

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Pica

SOURCES: MONDO OMIM UMLS GARD ORPHANET MESH

Medium match MONOCARBOXYLATE TRANSPORTER 1 DEFICIENCY; MCT1D

MONOCARBOXYLATE TRANSPORTER 1 DEFICIENCY; MCT1D Is also known as ;

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Global developmental delay
• Microcephaly

SOURCES: ORPHANET MONDO UMLS OMIM

Medium match NEPHROGENIC DIABETES INSIPIDUS

Nephrogenic diabetes insipidus (NDI) is characterized by polyuria with polydipsia, recurrent bouts of fever, constipation, and acute hypernatremic dehydration after birth that may cause neurological sequelae. Polyuria may exceed 10 litres in children.

• Seizures
• Global developmental delay
• Short stature
• Growth delay
• Failure to thrive

SOURCES: UMLS ICD10 ORPHANET

Medium match DIARRHEA 2, WITH MICROVILLUS ATROPHY; DIAR2

Microvillus inclusion disease (MVID) is characterized by onset of intractable life-threatening watery diarrhea during infancy. Two forms are recognized: early-onset MVID with diarrhea beginning in the neonatal period, and late-onset, with first symptoms appearing after 3 or 4 months of life. Definite diagnosis is made by transmission electron microscopy demonstrating shortening or absence of apical microvilli with pathognomonic microvillus inclusions in mature enterocytes and peripheral accumulation of periodic acid-Schiff (PAS)-positive granules or vesicles in immature enterocytes (Muller et al., 2008). The natural course of MVID is often fatal, but partial or total weaning from parenteral nutrition has been described.

DIARRHEA 2, WITH MICROVILLUS ATROPHY; DIAR2 Is also known as microvillus inclusion disease;mvid, microvillus atrophy, congenital, davidson disease, congenital familial protracted diarrhea with enterocyte brush-border abnormalities, intractable diarrhea of infancy;congenital microvillous atrophy; congenital microvillus atrophy; mvid; microvillous inclusion disease

• Autosomal recessive inheritance
• Global developmental delay
• Pica
• Growth delay
• Failure to thrive

SOURCES: GARD DOID UMLS ORPHANET OMIM SCTID MONDO

Medium match METHYLMALONYL-CoA EPIMERASE DEFICIENCY

Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency is a rare inborn error of metabolism disease characterized by mild to moderate, persistent elevation of methylmalonic acid in plasma, urine and cerebrospinal fluid. Clinical presentation may include acute metabolic decompensation with metabolic acidosis (presenting with vomiting, dehydration, confusion, hallucinations), nonspecific neurological symptoms, or may also be asymptomatic.

METHYLMALONYL-CoA EPIMERASE DEFICIENCY Is also known as methylmalonyl-coa racemase deficiency, methylmalonic aciduria iii, formerly;mcee deficiency; methylmalonic acidemia due to methylmalonyl-coa racemase deficiency; methylmalonic aciduria due to methylmalonyl-coa epimerase deficiency; methylmalonic aciduria due to methylmalonyl-coa racemase deficiency

• Autosomal recessive inheritance
• Failure to thrive
• Motor delay
• Spasticity
• Macrocephaly

SOURCES: MESH ORPHANET MONDO OMIM UMLS

Medium match ISOVALERIC ACIDEMIA; IVA

Isovaleric acidemia (IVA) is an autosomal recessively inherited organic aciduria characterized by a deficiency in isovaleryl-CoA dehydrogenase, that has wide clinical variability and that can present in infancy with acute manifestations of vomiting, failure to thrive, seizures, lethargy, a characteristic ''sweaty feet'' odor, acute pancreatitis and mild to severe developmental delay or in childhood with metabolic acidosis (brought on by prolonged fasting, an increased intake of protein-rich food or infections) and that can be fatal if not treated immediately. Chronic intermittent presentations and asymptomatic patients have also been reported.

ISOVALERIC ACIDEMIA; IVA Is also known as isovaleric acid coa dehydrogenase deficiency, ivd deficiency;isovaleric acid coa dehydrogenase deficiency

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Hepatomegaly
• Edema

SOURCES: SCTID NCIT OMIM MESH MONDO ICD10 ORPHANET GARD DOID UMLS

Medium match METHYLMALONIC ACIDURIA, cblB TYPE

Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin (cbl; vitamin B12) metabolism. Different forms of isolated methylmalonic aciduria have been classified according to complementation groups of cells in vitro. Patients with defects in the synthesis of AdoCbl are usually responsive to vitamin B12 therapy and are classified as 'cbl' type: these include cblB and cblA (OMIM ). The cblA type is caused by mutation in the MMAA gene (OMIM ). The 'mut' type (OMIM ) is caused by mutation in the MUT gene; in general, the mut form of MMA is unresponsive to vitamin B12 therapy.Combined methylmalonic aciduria and homocystinuria may be seen in complementation groups cblC (OMIM ), cblD (OMIM ), and cblF (OMIM ).

METHYLMALONIC ACIDURIA, cblB TYPE Is also known as methylmalonic acidemia, cblb type, methylmalonic aciduria, vitamin b12-responsive, due to defect in synthesis of adenosylcobalamin, cblb type;vitamin b12-responsive methylmalonic aciduria, type cblb

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

SOURCES: DOID UMLS OMIM MONDO ORPHANET GARD NCIT