Intellectual disability, and Pancreatitis

Vitamin B12-unresponsive methylmalonic acidemia type mut0 is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.

VITAMIN B12-UNRESPONSIVE METHYLMALONIC ACIDEMIA TYPE MUT0 Is also known as complete deficiency of methylmalonyl-coa mutase|vitamin b12-unresponsive methylmalonic aciduria type mut0

• Intellectual disability
• Global developmental delay
• Growth delay
• Muscular hypotonia
• Anemia

SOURCES: ORPHANET MENDELIAN

Nephronophthisis is an autosomal recessive cystic kidney disease characterized by onset of end-stage renal failure in the first 3 decades of life. The disorder is often associated with extrarenal manifestations, including liver fibrosis, retinal degeneration, and central nervous system abnormalities (summary by O'Toole et al., 2010).For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (OMIM ).

• Intellectual disability
• Seizures
• Hearing impairment
• Sensorineural hearing impairment
• Hypertension

SOURCES: OMIM MENDELIAN

Vitamin B12-unresponsive methylmalonic acidemia type mut- is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.

VITAMIN B12-UNRESPONSIVE METHYLMALONIC ACIDEMIA TYPE MUT- Is also known as vitamin b12-unresponsive methylmalonic aciduria type mut-|partial deficiency of methylmalonyl-coa mutase

• Intellectual disability
• Seizures
• Global developmental delay
• Failure to thrive
• Muscular hypotonia

SOURCES: ORPHANET MENDELIAN

Neutral lipid storage disease with myopathy is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011).Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS ) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007).

NEUTRAL LIPID STORAGE MYOPATHY Is also known as neutral lipid storage disease with myopathy without ichthyosis|nlsdm|triglyceride deposit cardiomyovasculopathy|neutral lipid storage disease without ichthyosis

• Short stature
• Generalized hypotonia
• Hearing impairment
• Sensorineural hearing impairment
• Muscle weakness

SOURCES: ORPHANET OMIM MENDELIAN

Classic maple syrup urine disease (classic MSUD) is the most severe and probably common form of MSUD (see this term) characterized by a maple syrup odor in the cerumen at birth, poor feeding, lethargy and focal dystonia, followed by progressive encephalopathy and central respiratory failure if untreated.

CLASSIC MAPLE SYRUP URINE DISEASE Is also known as keto acid decarboxylase deficiency|classic branched-chain ketoaciduria|classic branched-chain alpha-ketoacid dehydrogenase deficiency|classic msud|bckd deficiency|classic bckd deficiency|branched-chain ketoaciduria|branched-chain alpha-keto acid dehydroge

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

SOURCES: OMIM ORPHANET MENDELIAN

Ornithine transcarbamylase deficiency is an X-linked inborn error of metabolism of the urea cycle which causes hyperammonemia. The disorder is treatable with supplemental dietary arginine and low protein diet.Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: OTC deficiency, carbamyl phosphate synthetase deficiency (OMIM ), argininosuccinate synthetase deficiency, or citrullinemia (OMIM ), argininosuccinate lyase deficiency (OMIM ), and arginase deficiency (OMIM ).

ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO Is also known as ornithine carbamoyltransferase deficiency|otc deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Growth delay

SOURCES: ORPHANET OMIM MENDELIAN

Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes (Garg, 2004).For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (OMIM ).

LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 2; CGL2 Is also known as berardinelli-seip congenital lipodystrophy, type 2|brunzell syndrome, bscl2-related|lipoatrophic diabetes, congenital|seip syndrome|lipodystrophy, total, and acromegaloid gigantism|lipodystrophy, berardinelli-seip congenital, type 2|berardinelli syndrome

• Intellectual disability
• Cognitive impairment
• Hypertension
• Hepatomegaly
• Cardiomyopathy

SOURCES: OMIM MENDELIAN

Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin (cbl; vitamin B12) metabolism. Isolated methylmalonic aciduria is found in patients with mutations in the MUT gene causing partial, mut(-), or complete, mut(0), enzyme deficiency. This form is unresponsive to B12 therapy. Various forms of isolated methylmalonic aciduria also occur in a subset of patients with defects in the synthesis of the MUT coenzyme adenosylcobalamin (AdoCbl) and are classified according to complementation group: cblA (OMIM ), caused by mutation in the MMAA gene (OMIM ) on chromosome 4q31, and cblB (OMIM ), caused by mutation in the MMAB gene (OMIM ) on 12q24.Combined methylmalonic aciduria and homocystinuria may be seen in complementation groups cblC (OMIM ), cblD (OMIM ), and cblF (OMIM ).See the comprehensive review of Ledley (1990).

METHYLMALONIC ACIDURIA DUE TO METHYLMALONYL-COA MUTASE DEFICIENCY Is also known as methylmalonic acidemia due to methylmalonyl-coa mutase deficiency mma due to mcm deficiency|methylmalonic aciduria, mut type

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

SOURCES: ORPHANET OMIM MENDELIAN

Propionic acidemia (PA) is an organic aciduria caused by the deficient activity of the propionyl Coenzyme A carboxylase and is characterized by life threatening episodes of metabolic decompensation, neurological dysfunction and that may be complicated by cardiomyopathy.

PROPIONIC ACIDEMIA Is also known as glycinemia, ketotic|ketotic hyperglycinemia|propionyl-coa carboxylase deficiency|propionic aciduria|pcc deficiency|hyperglycinemia with ketoacidosis and leukopenia

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

SOURCES: ORPHANET OMIM MESH MENDELIAN

Classic homocystinuria is an autosomal recessive metabolic disorder of sulfur metabolism. The clinical features of untreated homocystinuria due to CBS deficiency usually manifest in the first or second decade of life and include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome (MFS ), and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine. There are 2 main phenotypes of the classic disorder: a milder pyridoxine (vitamin B6)-responsive form, and a more severe pyridoxine-nonresponsive form. Pyridoxine is a cofactor for the CBS enzyme, and can aid in the conversion of homocysteine to cysteine (summary by Reish et al., 1995 and Testai and Gorelick, 2010).Some patients have been reported to have a milder form of homocystinuria, which is characterized by increased plasma homocysteine and increased risk for thrombotic events in young adulthood, but without the other skeletal, ocular, or nervous system manifestations observed in classic homocystinuria (Kelly et al., 2003).

HOMOCYSTINURIA DUE TO CYSTATHIONINE BETA-SYNTHASE DEFICIENCY Is also known as cystathionine beta-synthase deficiency|cbs deficiency|homocystinuria with or without response to pyridoxine

• Intellectual disability
• Seizures
• Failure to thrive
• High palate
• Myopia

SOURCES: OMIM MENDELIAN