MedGen

The creatine deficiency disorders (CDDs), inborn errors of creatine metabolism and transport, comprise three disorders: the creatine biosynthesis disorders guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency; and creatine transporter (CRTR) deficiency. Developmental delay and cognitive dysfunction or intellectual disability and speech-language disorder are common to all three CDDs. Onset of clinical manifestations of GAMT deficiency (reported in ~130 individuals) is between ages three months and two years; in addition to developmental delays, the majority of individuals have epilepsy and develop a behavior disorder (e.g., hyperactivity, autism, or self-injurious behavior), and about 30% have movement disorder. AGAT deficiency has been reported in 16 individuals; none have had epilepsy or movement disorders. Clinical findings of CRTR deficiency in affected males (reported in ~130 individuals) in addition to developmental delays include epilepsy (variable seizure types and may be intractable) and behavior disorders (e.g., attention deficit and/or hyperactivity, autistic features, impulsivity, social anxiety), hypotonia, and (less commonly) a movement disorder. Poor weight gain with constipation and prolonged QTc on EKG have been reported. While mild-to-moderate intellectual disability is commonly observed up to age four years, the majority of adult males with CRTR deficiency have been reported to have severe intellectual disability. Females heterozygous for CRTR deficiency are typically either asymptomatic or have mild intellectual disability, although a more severe phenotype resembling the male phenotype has been reported. [from GeneReviews]

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. The syndrome manifests as an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolality, and natriuresis. SIADH occurs in a setting of normal blood volume, without evidence of renal disease or deficiency of thyroxine or cortisol. Although usually transient, SIADH may be chronic; it is often associated with drug use or a lesion in the central nervous system or lung. When the cardinal features of SIADH were defined by Bartter and Schwartz (1967), levels of AVP could not be measured. Subsequently, radioimmunoassays revealed that SIADH is usually associated with measurably elevated serum levels of AVP. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is characterized by a clinical picture similar to SIADH, but is associated with undetectable levels of AVP (Feldman et al., 2005). [from OMIM]

IMDDHH is a multisystem disorder characterized by immunodeficiency, mildly delayed psychomotor development, poor overall growth from infancy, and hypohomocysteinemia. Additional features, such as congenital heart defects and liver involvement, are more variable (summary by Huppke et al., 2017). [from OMIM]

Congenital disorder of glycosylation type IIt (CDG2t) is an autosomal recessive multisystemic metabolic disorder characterized by global developmental delay, poor overall growth, severely impaired intellectual development with absent language, and behavioral abnormalities. Most patients develop early-onset seizures; brain imaging tends to show white matter abnormalities. Variable dysmorphic features, including long face, almond-shaped eyes, protruding maxilla, and short philtrum, are also present. The disorder, which is associated with low levels of HDL cholesterol, results from defective posttranslational O-linked glycosylation of certain plasma lipids and proteins (summary by Zilmer et al., 2020). For an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066). [from OMIM]

An abnormally reduced amount of creatinine in the blood. [from HPO]