Ataxia, and Hepatosplenomegaly

X-linked sideroblastic anemia is a constitutional microcytic, hypochromic anemia of varying severity that is clinically characterized by manifestations of anemia and iron overload and that may respond to treatment with pyridoxine and folic acid.

X-LINKED SIDEROBLASTIC ANEMIA Is also known as anemia, hereditary sideroblastic|xlsa|anemia, hypochromic|anemia, sideroblastic, x-linked|anh1|hereditary iron-loading anemia

• Ataxia
• Muscle weakness
• Anemia
• Hepatomegaly
• Fatigue

SOURCES: ORPHANET OMIM MENDELIAN

Severe congenital neutropenia-3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities (summary by Boztug et al., 2010).The Swedish physician Rolf Kostmann (1956) described an autosomal recessive hematologic disorder, termed infantile agranulocytosis, with severe neutropenia with an absolute neutrophil count below 0.5 x 10(9)/l and early onset of severe bacterial infections. The disorder was later termed Kostmann syndrome (Skokowa et al., 2007). Lekstrom-Himes and Gallin (2000) discussed severe congenital neutropenia in a review of immunodeficiencies caused by defects in phagocytes.In addition to Kostmann agranulocytosis, recessively inherited neutropenic syndromes include congenital neutropenia with eosinophilia (OMIM ), Chediak-Higashi syndrome (OMIM ), and Fanconi pancytopenic syndrome (see {227650}).For a phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (OMIM ).

NEUTROPENIA, SEVERE CONGENITAL, 3, AUTOSOMAL RECESSIVE; SCN3 Is also known as agranulocytosis, infantile|kostmann disease

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

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

• Seizures
• Ataxia
• Anemia
• Dysarthria
• Tremor

SOURCES: OMIM MESH ORPHANET MENDELIAN

Phosphoglycerate kinase-1 deficiency is an X-linked recessive condition with a highly variable clinical phenotype that includes hemolytic anemia, myopathy, and neurologic involvement. Patients can express 1, 2, or all 3 of these manifestations (Shirakawa et al., 2006).

PHOSPHOGLYCERATE KINASE 1 DEFICIENCY Is also known as pgk1 deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Ataxia

SOURCES: MESH OMIM MENDELIAN

Niemann-Pick type C (NPC) disease is an autosomal recessive lipid storage disorder characterized by progressive neurodegeneration. Approximately 95% of cases are caused by mutations in the NPC1 gene (OMIM ), referred to as type C1 (OMIM ); 5% are caused by mutations in the NPC2 gene (OMIM ), referred to as type C2. The clinical manifestations of types C1 (OMIM ) and C2 are similar because the respective genes are both involved in egress of lipids, particularly cholesterol, from late endosomes or lysosomes (summary by Vance, 2006).

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

SOURCES: OMIM MESH MENDELIAN

Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG ) and TNF-alpha (OMIM ), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004).For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see {267700}.

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 2; FHL2 Is also known as hplh2|hlh2

• Seizures
• Global developmental delay
• Generalized hypotonia
• Ataxia
• Failure to thrive

SOURCES: OMIM MENDELIAN

CHANARIN-DORFMAN SYNDROME; CDS Is also known as neutral lipid storage disease with ichthyosis|dcs|nlsdi|triglyceride storage disease with impaired long-chain fatty acid oxidation|dorfman-chanarin syndrome|chanarin-dorfman disease|ichthyosiform erythroderma with leukocyte vacuolation|ichthyotic neutral

• Intellectual disability
• Global developmental delay
• Short stature
• Hearing impairment
• Ataxia

SOURCES: OMIM ORPHANET MENDELIAN

Hereditary cryohydrocytosis with reduced stomatin is a rare hemolytic anemia characterized by combination of neurologic features, such as psychomotor delay, seizures, variable movement disorders, and hemolytic anemia with stomatocytosis, resulting in cation-leaky erythrocytes, pseudohyperkalemia, hemolytic crises and hepatosplenomegaly. Cataracts are also a presenting feature.

HEREDITARY CRYOHYDROCYTOSIS WITH REDUCED STOMATIN Is also known as cryohydrocytosis, stomatin-deficient, with mental retardation, seizures, cataracts, and massive hepatosplenomegaly|hereditary cryohydrocytosis type 2|sdchc|stomatin-deficient cryohydrocytosis|chc type 2|glut1 deficiency syndrome with pseudohyperkalemia an

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Microcephaly

SOURCES: ORPHANET MESH OMIM MENDELIAN

A congenital disease caused by an inborn error involving APOLIPOPROTEINS E leading to abnormal LIPID METABOLISM and the accumulation of GLYCOSPHINGOLIPIDS, particularly SPHINGOMYELINS in the HISTIOCYTES. This disorder is characterized by SPLENOMEGALY and the sea-blue histiocytes in the spleen and bone marrow after May Grunwald staining.

SEA-BLUE HISTIOCYTOSIS Is also known as sea-blue histiocytosis|histiocytosis, sea-blue

• Seizures
• Ataxia
• Peripheral neuropathy
• Hepatomegaly
• Gait disturbance

SOURCES: OMIM MESH ORPHANET MENDELIAN