Motor delay, and Splenomegaly

Glycogen storage disease (GSD) due to liver phosphorylase kinase (PhK) deficiency is a benign inborn error of glycogen metabolism characterized by hepatomegaly, growth retardation, and mild delay in motor development during childhood.

GLYCOGEN STORAGE DISEASE DUE TO LIVER PHOSPHORYLASE KINASE DEFICIENCY Is also known as gsd type ixc|gsd due to liver phosphorylase kinase deficiency|xlg|glycogen storage disease type 9c|glycogen storage disease type 9a|gsd ixc|gsd type 9c|glycogen storage disease type ixc|glycogenosis due to liver phosphorylase kinase deficiency|glycogenosi

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

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

Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015).

ACUTE INFANTILE LIVER FAILURE-CEREBELLAR ATAXIA-PERIPHERAL SENSORY MOTOR NEUROPATHY SYNDROME Is also known as spinocerebellar ataxia, autosomal recessive 21, with hepatopathy|autosomal recessive spinocerebellar ataxia type 21|scar21

• Intellectual disability
• Global developmental delay
• Ataxia
• Muscle weakness
• Spasticity

SOURCES: ORPHANET OMIM MENDELIAN

Purine nucleoside phosphorylase (PNP) deficiency is a disorder of purine metabolism characterized by progressive immunodeficiency leading to recurrent and opportunistic infections, autoimmunity and malignancy as well as neurologic manifestations.

PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCY Is also known as pnp deficiency|pnpase deficiency|nucleoside phosphorylase deficiency

• Intellectual disability
• Generalized hypotonia
• Ataxia
• Failure to thrive
• Muscular hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Triosephosphate isomerase (TPI) deficiency is a severe autosomal recessive inherited multisystem disorder of glycolytic metabolism characterized by hemolytic anemia and neurodegeneration.

• Seizures
• Global developmental delay
• Generalized hypotonia
• Muscle weakness
• Muscular hypotonia

SOURCES: ORPHANET MESH OMIM MENDELIAN

Hermansky-Pudlak syndrome type 2 (HPS-2) is a type of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and neutropenia.

HERMANSKY-PUDLAK SYNDROME WITH NEUTROPENIA Is also known as hps2|hermansky-pudlak syndrome type 2

• Intellectual disability
• Global developmental delay
• Hearing impairment
• Microcephaly
• Nystagmus

SOURCES: OMIM MESH ORPHANET MENDELIAN

Adams-Oliver syndrome (AOS) is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). In addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrently seen. Congenital heart defects have been estimated to be present in 20% of AOS patients; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot (summary by Stittrich et al., 2014).For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (OMIM ).

• Seizures
• Global developmental delay
• Short stature
• Muscle weakness
• Motor delay

SOURCES: OMIM MENDELIAN

Sanfilippo syndrome comprises several forms of lysosomal storage diseases due to impaired degradation of heparan sulfate. The deficient enzyme in Sanfilippo syndrome C, or MPS IIIC, is an acetyltransferase that catalyzes the conversion of alpha-glucosaminide residues to N-acetylglucosaminide in the presence of acetyl-CoA.For a general phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, see MPS IIIA (OMIM ).

MUCOPOLYSACCHARIDOSIS, TYPE IIIC; MPS3C Is also known as sanfilippo syndrome c|mps iiic|acetyl-coa:alpha-glucosaminide n-acetyltransferase deficiency

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

SOURCES: OMIM MENDELIAN

Farber disease is a rare sphingolipid disorder characterized by a spectrum of clinical signs ranging from the classical triad of painful and progressively deformed joints, subcutaneous nodules, and progressive hoarseness (due to laryngeal involvement) that presents in infancy, to varying phenotypes with respiratory and neurologic involvement.

FARBER DISEASE Is also known as acid ceramidase deficiency|ac deficiency|farber lipogranulomatosis|ceramidase deficiency|farber disease|n-laurylsphingosine deacylase deficiency

• Intellectual disability
• Global developmental delay
• Short stature
• Nystagmus
• Failure to thrive

SOURCES: ORPHANET OMIM MESH MENDELIAN

Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease (PCWH) is a systemic disease characterized by the association of the features of Waardenburg-Shah syndrome (WSS) with neurological features of variable severity.

PERIPHERAL DEMYELINATING NEUROPATHY-CENTRAL DYSMYELINATING LEUKODYSTROPHY-WAARDENBURG SYNDROME-HIRSCHSPRUNG DISEASE Is also known as neurologic waardenburg-shah syndrome|waardenburg-shah syndrome, neurologic variant|pcwh|ws4 plus

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

SOURCES: OMIM MESH ORPHANET MENDELIAN