Generalized hypotonia, and Jaundice

Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see {214100}.Individuals with PBDs of complementation group 9 (CG9, equivalent to CGD) have mutations in the PEX16 gene. For information on the history of PBD complementation groups, see {214100}.

• Seizures
• Generalized hypotonia
• Muscular hypotonia
• Cataract
• Hepatomegaly

SOURCES: OMIM MENDELIAN

Acute infantile liver failure due to mtDNA-encoded proteins synthesis defect is a very rare mitochondrial respiratory chain deficiency described in fewer than 10 infants, primarily of middle Eastern descent, and characterized clinically by transient but life-threatening liver failure with elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, and lactic acidemia.

ACUTE INFANTILE LIVER FAILURE DUE TO SYNTHESIS DEFECT OF MTDNA-ENCODED PROTEINS Is also known as acute infantile liver failure due to synthesis defect of mitochondrial dna-encoded proteins

• Generalized hypotonia
• Feeding difficulties
• Hepatomegaly
• Myopathy
• Vomiting

SOURCES: OMIM ORPHANET MENDELIAN

Epimerase-deficiency galactosemia was originally described as a benign condition in which GALE impairment is restricted to circulating red and white blood cells (Gitzelmann, 1972). Fibroblasts, liver, phytohemagglutinin-stimulated leukocyes, and Epstein Barr virus-transformed lymphoblasts from these patients all demonstrated normal or near-normal levels of GALE, leading to the designation 'peripheral' (or 'isolated') epimerase deficiency. A second form of epimerase deficiency became apparent in which a patient, despite normal GALT activity, presented with symptoms reminiscent of classic galactosemia and demonstrated severely impaired GALE activity in both red blood cells and fibroblasts (Holton et al., 1981). This form was designated 'generalized' epimerase deficiency. Openo et al. (2006) demonstrated that epimerase deficiency is in fact not a binary condition but is, rather, a continuum disorder.GALE encodes the third enzyme in the Leloir pathway of galactose metabolism. Galactosemia I is classic galactosemia (OMIM ), caused by deficiency of the second enzyme in the Leloir pathway, galactose-1-phosphate uridylyl-transferase (GALT ). Galactosemia II (OMIM ) is caused by deficiency of the first enzyme in the Leloir pathway, galactokinase (GALK ).

GALACTOSE EPIMERASE DEFICIENCY Is also known as udp-galactose-4-epimerase deficiency|gale deficiency|galactosemia iii

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

SOURCES: ORPHANET OMIM MENDELIAN

Resistance to thyrotropin-releasing hormone (TRH) syndrome is a type of central congenital hypothyroidism (see this term) characterized by low levels of thyroid hormones due to insufficient release of thyroid-stimulating hormone (TSH) caused by pituitary resistance to TRH. It may or may not be observed from birth.

RESISTANCE TO THYROTROPIN-RELEASING HORMONE SYNDROME Is also known as trh resistance syndrome|central hypothyroidism due to trh receptor deficiency

• Global developmental delay
• Generalized hypotonia
• Growth delay
• Muscular hypotonia
• Feeding difficulties

SOURCES: ORPHANET MENDELIAN

• Seizures
• Global developmental delay
• Generalized hypotonia
• Nystagmus
• Cataract

SOURCES: OMIM MENDELIAN

Congenital disorder of glycosylation type IIo (CDG2O) is an autosomal recessive metabolic disorder characterized by infantile onset of progressive liver failure, hypotonia, and delayed psychomotor development. Laboratory abnormalities include elevated liver enzymes, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect (summary by Jansen et al., 2016).For a general discussion of CDGs, see CDG1A (OMIM ).

CCDC115-CDG Is also known as cdgiio|carbohydrate deficient glycoprotein syndrome type iio|congenital disorder of glycosylation type 2o|cdg-iio|cdg syndrome type iio|cdg iio|cdg2o|congenital disorder of glycosylation type iio

• Seizures
• Global developmental delay
• Generalized hypotonia
• Ptosis
• Hepatomegaly

SOURCES: OMIM ORPHANET MENDELIAN

• Generalized hypotonia
• Muscular hypotonia
• Vomiting
• Jaundice
• Hypoglycemia

SOURCES: OMIM MESH MENDELIAN

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

SOURCES: MESH OMIM MENDELIAN

Lipoyl transferase 1 deficiency is a very rare inborn error of metabolism disorder, with a highly variable phenotype, typically characterized by neonatal to infancy-onset of seizures, psychomotor delay, and abnormal muscle tone that may include hypo- and/or hypertonia, resulting in generalized weakness, dystonic movements, and/or progressive respiratory distress, associated with severe lactic acidosis and elevated lactate, ketoglutarate and 2-oxoacids in urine. Additional manifestations may include dehydration, vomiting, signs of liver dysfunction, extrapyramidal signs, spastic tetraparesis, brisk deep tendon reflexes, speech impairment, swallowing difficulties, and pulmonary hypertension.

• Global developmental delay
• Generalized hypotonia
• Hypertension
• Cerebellar atrophy
• Hypertonia

SOURCES: ORPHANET OMIM MENDELIAN

CRIGLER-NAJJAR SYNDROME, TYPE I Is also known as crigler-najjar syndrome|hyperbilirubinemia, crigler-najjar type i|hblrcn1

• Intellectual disability
• Seizures
• Generalized hypotonia
• Hearing impairment
• Spasticity

SOURCES: OMIM MENDELIAN